Protective effect of NLRP12 knockdown on retinal damage in rats with ocular hypertension and its mechanism of inhibiting cell pyroptosis / 中华实验眼科杂志

Objective:To investigate the effect and mechanism of NOD-like receptor family pyrin domain containing 12 (NLRP12) knockdown on inflammatory factor levels and retinal injury in retinal ganglion cells (RGCs) of rats with high intraocular pressure.Methods:Seventy SPF adult male SD rats were selected and randomized into control group, high intraocular pressure (IOP) group, high IOP+ small interfering RNA negative control (siNC) group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ recombinant rat caspase-1 (rrcaspase-1) group, with 14 rats in each group.Rats in the control group were only treated with conjunctival incision in the right eye, and ocular hypertension model was established in the other four groups with external scleral vein cauterization.High IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group were injected with siNC, siNLRP12 and siNLRP12+ rrcaspase-1 reagent via the tail vein, respectively.The IOP of the right eye was measured at 1 day, 1, 2 and 3 weeks after the operation.Three weeks after the operation, the retinal structure was observed by hematoxylin-eosin staining, and the number of RGCs in each group was counted.RGCs were divided into control group, rrcaspase-1 group, siNC+ rrcaspase-1 group, siNLRP12+ rrcaspase-1 group.The cells in rrcaspase-1 group, siNC+ rrcaspase-1 group and siNLRP12+ rrcaspase-1 group were treated with rrcaspase-1, siNC+ rrcaspase-1 and siNLRP12+ rrcaspase-1 reagent for 24 hours, respectively.No treatment was given to the control group.The expression levels of NLRP12, caspase-1 and cleaved-caspase-1 proteins in RGCs and retinal tissue were detected by Western blot.The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat serum or cell culture supernatant were detected by enzyme-linked immunosorbent assay.The study protocol was approved by the Animal Ethics Committee of the First People's Hospital of Chenzhou (No.2020086).Results:Compared with control group, the IOP was higher in high IOP group at 1, 2 and 3 weeks after cauterization, and the differences were statistically significant (all at P<0.05). The retinal tissue was clear with the RGCs in a single layer arrangement in the control group.In the high IOP group and the high IOP+ siNC group, the RGCs layer was loose and the inner plexiform layer was thin.The inner plexiform layer was thickened in high IOP+ siNLRP12 group compared with high IOP group, and the RGCs layer was loose in the high IOP+ siNLRP12 group and the high IOP+ siNLRP12+ rrcaspase-1 group.The number of RGCs in control group, high IOP group, high IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group was 119.31±23.25, 89.19±16.98, 88.87±13.92, 109.33±10.25 and 92.89±12.58, respectively, showing a statistically significant overall difference ( F=201.932, P<0.001). The number of RGCs was lower in the high IOP group, high IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group than the control group, higher in the high IOP+ siNLRP12 group than the high IOP+ siNC group, and lower in the high IOP+ siNLRP12+ rrcaspase-1 group than the high IOP+ siNLRP12 group, and the differences were statistically significant (all at P<0.05). The relative expressions of caspase-1 and cleaved-caspase-1 proteins and the concentrations of TNF-α and IL-1β in the retinal tissue were higher in high IOP group, high IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group than control group, higher in high IOP+ siNLRP12 group than high IOP+ siNC group, and higher in high IOP+ siNLRP12+ rrcaspase-1 group than high IOP+ siNLRP12 group (all at P<0.05). Relative expression levels of caspase-1 and cleaved-caspase-1 protein were increased in rrcaspase-1 group and siNC+ rrcaspase-1 group compared with control group, and relative expression levels of NLRP12, caspase-1 and cleaved-caspase-1 protein were decreased in siNLRP12+ rrcaspase-1 group compared with control group (all at P<0.05). The relative mass concentrations of TNF-α and IL-1β were increased in rrcaspase-1 group, siNC+ rrcaspase-1 group and siNLRP12+ rrcaspase-1 group compared with the control group (all at P<0.05). Relative expression levels of NLRP12, caspase-1 and cleaved-caspase-1 proteins and relative mass concentrations of TNF-α and IL-1β in siNLRP12+ rrcaspase-1 group were lower than those in siNC+ rrcaspase-1 group (all at P<0.05). Conclusions:Knockdown of NLRP12 can reduce the inflammatory response and retinal injury induced by high IOP by inhibiting the activation of caspase-1.

Inhibition and Mechanism of Imatinib on A549 Xenograft Tumor in Nude Mice via PDGF/PDGFR Pathway / 肿瘤防治研究

Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.

Börjeson -Forssman -Lehmann syndrome: A case report / 中南大学学报(医学版)

Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of PHF6 gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the PHF6 (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.

Factors associated with readmission within three months of surgery for gastric cancer and their long-term effects on patients' nutritional status and quality of life / 中华胃肠外科杂志

Objective: To analyze the factors associated with readmission within three months of surgery for gastric cancer and the impact of readmission on patients' long-term nutritional status and quality of life. Methods: This was a prospective cohort study comprising patients who underwent radical gastrectomy in the Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences from October 2018 to August 2019. Patients who failed to complete postoperative follow-up, whose body mass index (BMI) could not be accurately estimated, or who were unable to complete a quality-of-life questionnaire were excluded. The patients were followed up for 12 months. Time to, cause(s) of, and outcomes of readmission were followed up 1, 2 and 3 months postoperatively. BMI was followed up 1, 3, 6 and 12 months postoperatively. Results of blood tests were collected and patients' nutritional status and quality of life were assessed 12 months postoperatively. Nutritional status was evaluated by BMI, hemoglobin, albumin, and total lymphocyte count. Quality of life was evaluated using the European Organization for Research in the Treatment of Cancer (EORTC) Quality of Life scale. The higher the scores for global health and functional domains, the better the quality of life, whereas the higher the score in the symptom domain, the worse the quality of life. Results: The study cohort comprised 259 patients with gastric cancer, all of whom were followed up for 3 months and 236 of whom were followed up for 12 months. Forty-four (17.0%) patients were readmitted within 3 months. The commonest reasons for readmission were gastrointestinal dysfunction (16 cases, 36.3%), intestinal obstruction (8 cases, 18.2%), and anastomotic stenosis (8 cases, 18.2%). Logistic regression analysis showed that preoperative Patient-Generated Subjective Global Assessment score ≥ 4 points (OR=1.481, 95% CI: 1.028‒2.132), postoperative complications (OR=3.298, 95%CI:1.416‒7.684) and resection range (OR=1.582, 95% CI:1.057‒2.369) were risk factors for readmission within 3 months of surgery. Compared with patients who had not been readmitted 12 months after surgery, patients who were readmitted within 3 months of surgery tended to have greater decreases in their BMI [-2.36 (-5.13,-0.42) kg/m2 vs. -1.73 (-3.33,-0.33) kg/m2, Z=1.850, P=0.065), significantly lower hemoglobin and albumin concentrations [(122.1±16.6) g/L vs. (129.8±18.4) g/L, t=2.400, P=0.017]; [(40.9±5.0) g/L vs. (43.4±3.3) g/L, t=3.950, P<0.001], and significantly decreased global health scores in the quality of life assessment [83 (67, 100) vs. 100 (83, 100), Z=2.890,P=0.004]. Conclusion: Preoperative nutritional risk, total or proximal radical gastrectomy, and complications during hospitalization are risk factors for readmission within 3 months of surgery for gastric cancer. Perioperative management and postoperative follow-up should be more rigorous. Readmission within 3 months after surgery may be associated with a decline in long-term nutritional status and quality of life. Achieving improvement in long-term nutritional status and quality of life requires tracking of nutritional status, timely evaluation, and appropriate interventions in patients who need readmission.

Factors influencing the efficacy of initial adrenocorticotropic hormone therapy for infantile epileptic spasms syndrome / 中国当代儿科杂志

OBJECTIVES@#To study the factors influencing the short-term (28 days) efficacy of initial adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasms syndrome (IESS), as well as the factors influencing recurrence and prognosis.@*METHODS@#The clinical data were collected from the children with IESS who received ACTH therapy for the first time in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from April 2008 to January 2018 and were followed up for ≥2 years. The multivariate logistic regression analysis was used to evaluate the factors influencing the short-term efficacy of ACTH therapy, recurrence, and long-term prognosis.@*RESULTS@#ACTH therapy achieved a control rate of seizures of 55.5% (111/200) on day 28 of treatment. Of the 111 children, 75 (67.6%) had no recurrence of seizures within 12 months of follow-up. The possibility of seizure control on day 28 of ACTH therapy in the children without focal seizures was 2.463 times that in those with focal seizures (P<0.05). The possibility of seizure control on day 28 of ACTH therapy in the children without hypsarrhythmia on electroencephalography on day 14 of ACTH therapy was 2.415 times that in those with hypsarrhythmia (P<0.05). The possibility of recurrence within 12 months after treatment was increased by 11.8% for every 1-month increase in the course of the disease (P<0.05). The possibility of moderate or severe developmental retardation or death in the children without seizure control after 28 days of ACTH therapy was 8.314 times that in those with seizure control (P<0.05). The possibility of moderate or severe developmental retardation or death in the children with structural etiology was 14.448 times that in those with unknown etiology (P<0.05).@*CONCLUSIONS@#Presence or absence of focal seizures and whether hypsarrhythmia disappears after 14 days of treatment can be used as predictors for the short-term efficacy of ACTH therapy, while the course of disease before treatment can be used as the predictor for recurrence after seizure control by ACTH therapy. The prognosis of IESS children is associated with etiology, and early control of seizures after ACTH therapy can improve long-term prognosis.

Clinical Significance of co-expression of RNA Binding Protein PTBP1 and p-AXL in Osteosarcoma / 中山大学学报(医学科学版)

ObjectiveTo explore the co-expression of PTBP1 and p-AXL in osteosarcoma and its clinicopathological significance for prognosis evaluation. MethodsThe expression of PTBP1 and AXL and their prognostic value in osteosarcoma were analyzed by GEO and Target data. Paraffin biopsy specimens and clinical information from 76 cases of osteosarcoma and 37 cases of non-malignant bone tissue （callus， osteofibrous dysplasia and osteoid ostema） were obtained from the First Affiliated Hospital of Sun Yat-sen University from March 2016 to October 2020. The expressions of PTBP1 and p-AXL proteins in osteosarcoma were detected by immunohistochemistry. ResultsGEO database showed that the expression levels of PTBP and AXL in osteosarcoma tumor group were higher than those in normal tissues， but did not reach statistical significance. Target database showed that the high expression of PTBP1 had shorter Overall survival（OS） and Progression-free survival（PFS） than low PTBP1 expression， but did not reach statistical significance （P=0.064； P=0.134）. Immunohistochemical staining included 76 cases of osteosarcoma and 37 cases of non-malignant bone tissue. The expression rate of PTBP1 and p-AXL protein in osteosarcoma tissues was higher than that in non-malignant bone tissue. The expression of p-AXL is correlated with lung metastasis （P=0.025）. Kaplan-Meier analysis showed that lung metastasis， recurrence， PTBP1 expression， co-expression of PTBP1/p-AXL influence the prognosis of patients in OS. Multivariate Cox regression analysis showed that lung metastasis （P<0.000 1） and positive expression of PTBP1 （P=0.041） were independent risk factors for osteosarcoma patients in OS. Co-expression of PTBP1 and p-AXL had shorter OS （P=0.017） and PFS （P=0.043） than non-coexpression osteosarcoma patients. ConclusionsPTBP1 and p-AXL were highly expressed in osteosarcoma tissues. The co-expression of PTBP1 and p-AXL was associated with poor prognosis of patients， and PTBP1 could be used as an independent prognostic indicator of patients with osteosarcoma.

Analysis of risk factors for pathological diagnosis upgrading after resection of colorectal adenoma / 中华消化杂志

Objective:To investigate the risk factors that affected pathological diagnosis upgrading after resection of colorectal adenoma.Methods:From January 2017 to December 2022, a total of 1 059 patients who underwent adenoma resection after pathologically diagnosed as adenoma by endoscopic forceps biopsy(EFB)were included in General Hospital of Ningxia Medical University. The patients were divided into the pathologically no difference group (1 003 cases) and the pathologically upgraded group (56 cases) based on the comparison of pathological diagnosis of EFB specimens and the specimens after adenoma resection. Clinical information and endoscopic characteristics of the adenoma were compared between the 2 groups. The clinical information included smoking history, family history of colorectal cancer, and the endoscopic characteristics included maximum diameter, morphological characteristics, surface depression, erosion or ulceration, and surface color of adenoma. Chi-square test and Fisher′s exact test were used for statistical analysis. Multivariate logistic regression model was used to analyze the risk factors for pathological diagnosis upgrading after adenoma resection.Results:The proportions of patients with smoking history, family history of colorectal cancer, concomitant hypertension, and coronary heart disease in the pathologically upgraded group were higher than those in the pathologically no difference group (46.43%, 26/56 vs.26.12%, 262/1 003; 8.93%, 5/56 vs.0.70%, 7/1 003; 46.43%, 26/56 vs.30.11%, 302/1 003; 21.43%, 12/56 vs.9.27%, 93/1 003), and the differences were statistically significant( χ2=11.05, Fisher′s exact test, χ2=6.61 and 8.78; all P<0.05). There were statistically significant differences between the pathologically no difference group and pathologically upgraded group in the maximum diameter (929 cases (92.62%) and 23 cases (41.07%) of < 20 mm, and 74 cases (7.38%) and 33 cases (58.93%) of ≥20 mm, respectively), morphological characteristics (220 cases (21.93%) and 28 cases (50.00%) with pedicle, and 783 cases (78.07%) and 28 cases (50.00%) without pedicle, respectively), surface color (347 cases (34.60%) and 3 cases (5.36%) of near normal mucosa, 613 cases (61.12%) and 50 cases (89.29%) of red surface color, and 43 cases (4.29%) and 3 cases (5.36%) of white surface color, respectively), erosion or ulceration (78 cases (7.78%) and 36 cases (64.29%) had erosion or ulceration, and 925 cases (92.22%) and 20 cases (35.71%) had no erosion or ulceration, respectively), and surface depression (6 cases (0.60%) and 8 cases (14.29%) of depression, and 997 cases (99.40%) and 48 cases (85.71%) of non depression, respectively) ( χ2=155.18, 23.30, 20.58 and 176.31, Fisher′s exact test; all P<0.001). The result of multivariate logistic regression analysis showed that surface depression ( OR=25.198, 95% confidence interval (95% CI) 5.812 to 109.246, P<0.001), erosion or ulceration( OR=9.913, 95% CI 4.652 to 21.124, P<0.001), red surface color ( OR=4.276, 95% CI 1.053 to 17.363, P=0.042), white surface color ( OR=8.803, 95% CI 1.398 to 55.435, P=0.021), maximum diameter≥20 mm ( OR=4.689, 95% CI 2.265 to 9.706, P<0.001), family history of colorectal cancer ( OR=8.764, 95% CI 1.418 to 54.162, P=0.019) and smoking history ( OR=2.713, 95% CI 1.376 to 5.349, P=0.004) were independent risk factors for pathological diagnosis upgrading after adenoma resection. Conclusion:Surface depression, maximum diameter ≥20 mm, erosion or ulceration, white or red surface color, family history of colorectal cancer and smoking history may enhance the heterogeneity of adenomas, interfere with the accuracy of EFB pathology, and lead to an upgrade of pathological diagnosis after adenoma resection.

CHESS endoscopic ruler in objective measurement of diameter of esophageal varices in liver cirrhosis and portal hypertension: a prospective multicenter study / 中华消化杂志

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Inherited protein C deficiency in pregnancy: a case report / 中华围产医学杂志

This paper reported the management of a pregnant women with inherited protein C deficiency. The patient had a history of recurrent deep vein thrombosis before pregnancy and was diagnosed with inherited protein C deficiency by a pedigree-based whole exome sequencing, which revealed PROC gene mutations. She received anticoagulation treatment and was managed by a multidisciplinary team during pregnancy. No significant abnormalities were found during routine prenatal examination and a male infant was delivered vaginally at 38 +2 gestational weeks. No postpartum hemorrhage was reported and the maternal and infant outcomes were good. The management of such patients during pregnancy mainly relied on anticoagulation therapy to avoid serious thrombotic events and ensure the safety of the mothers and fetuses.

Two consecutive pregnancies of a woman with severe pulmonary arterial hypertension associated with connective tissue disease / 中华围产医学杂志

Pulmonary arterial hypertension (PAH) is an abnormal remodeling of the pulmonary vascular wall due to various causes, resulting in severe cardiovascular disease characterized by increased pulmonary vascular resistance and pressure. The mortality and morbidity of pregnant women with PAH are extremely high. This article reports a woman with severe PAH associated with connective tissue disease who developed cardiac arrest, PAH crisis, and right heart failure during her two consecutive pregnancies without regular prenatal examination. After multidisciplinary consultation and extracorporeal membrane oxygenation, effective cardiopulmonary support was timely, and the patient was finally discharged from the hospital in stable condition. After ten months of follow-up, the mother and child both had good outcomes. Although the mother and her child were survived, severe PAH is a contraindication for pregnancy due to its severely harmful effect on endangering maternal and fetal health.

Global developmental delay and epileptic encephalopathy caused by SPTAN1 gene mutations in 3 cases and literature review / 中华神经科杂志

Objective:To summarize the clinical manifestations, gene variations,and treatment of cases with SPTAN1 gene variations characterized by global developmental delay or epileptic encephalopathy. Methods:Three patients with SPTAN1 gene mutations which caused developmental epileptic encephalopathy type 5 admitted to the Department of Pediatrics, Xiangya Hospital, Central South University from August 2019 to September 2021 were collected. The studies till December 2021 were searched with keywords of " SPTAN1" and "developmental and epileptic encephalopathy 5" in both English and Chinese databases of China National Knowledge Infrastructure, Wanfang, Online Mendelian Inheritance in Man, and PubMed. The clinical manifestations, genetic variations, treatments and prognosis of patients with SPTAN1 gene variations were summarized. Results:All 3 patients presented with global developmental delay, infant onset. Patient 1 showed early-onset epileptic encephalopathies and microcephaly. Patient 2 had an atrial septal defect. Cranial magnetic resonance imaging (MRI) of patient 3 showed cerebellar hypoplasia.Antiepileptic seizure therapy was partially effective, but failed to control the spasm. Development was slightly improved after rehabilitation training and other treatments, but still lagged behind the children of the same age. The SPTAN1 gene mutations of the 3 cases were heterozygous mutations, c.6923_6928dup, c.6619_6621delGAG and c.6749T>C, respectively. c.6749T>C was not reported in the previous literature. Thirteen case reports, including 69 patients, were collected. Sixty-seven patients had heterozygous mutations, inherited in an autosomal dominant fashion, including 35 missense mutations, 12 deletion mutations, 11 repetition mutations, 9 nonsense mutations, and the rest 2 patients had compound heterozygous missense mutations. A total of 38 different variation sites were reported. The phenotypes of 69 patients from the previous studies mainly included intellectual impairment (32/69), seizures (30/69), developmental delay (28/69), progressive microcephaly (27/69), hypotonia (23/69), poor visual attention (15/69), spastic quadriplegia (9/69), and gastrointestinal abnormalities (7/69). The primary type of seizures was epileptic spasm. Cranial MRI abnormalities mainly included cerebellar and brainstem atrophy, corpus callosum dysplasia, myelin dysplasia, and brain atrophy. Previous reports showed that a variety of anti-seizure drugs were effective for epileptic seizures. The prognosis varied greatly. Severe cases could be fatal, and mild cases only manifested as mild mental retardation or movement disorders. Conclusions:SPTAN1 gene mutation leads to developmental epileptic encephalopathy type 5, the phenotypes of which include intellectual impairment, global developmental delay, infantile spasms, and head deformity.Antiepileptic drugs and functional training can improve the symptoms, but the prognosis is still poor. This study expands the SPTAN1 gene variant spectrum, enriches the mutant spectrum of SPTAN1 gene associated with developmental epileptic encephalopathy type 5.

Outcomes of the second pregnancy after Triple-P procedure in women complicated with placenta accreta spectrum disorders / 中华妇产科杂志

Objective:To investigate the safety of the Triple-P procedure in women complicated with severe placenta accreta spectrum disorders (PAS) and its influence on second pregnancy.Methods:From January 2015 to December 2017, the outcomes of the second pregnancy after the Triple-P procedure in 11 pregnant women complicated with PAS in the Third Affiliated Hospital of Guangzhou Medical University and the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Results:By December 2021, a total of 11 pregnant women who underwent the Triple-P procedure for PAS had a second pregnancy, with a median interval of 3 years (2-3 years). Of the 11 pregnant women, 7 delivered after 36 weeks of gestation. The median gestational age was 38 weeks, and 4 terminated within the first trimester. PAS recurred in 1 of 7 pregnant women (1/7) and was associated with placenta previa. All of the 7 pregnant women were delivered by cesarean section, with a median postpartum blood loss of 300 ml (200-450 ml), and only one pregnant woman required blood transfusion. None of the pregnant women were transferred to the intensive care unit, and there were no uterine rupture, bladder injury, puerperal infection, and neonatal adverse outcomes.Conclusion:Pregnant women who underwent the Triple-P procedure for severe PAS could be considered for second pregnancy with strictly management by an experienced multidisciplinary team, which may result in a good outcome.

Analysis of the efficacy and related influencing factors of pelvic packing in the treatment of intractable postpartum hemorrhage after emergency perinatal hysterectomy / 中华妇产科杂志

Objective:To investigate the effect of pelvic packing on the control of intractable postpartum hemorrhage after emergency perinatal hysterectomy (EPH).Methods:Eleven cases with complete clinical data of pelvic packing due to failure of hemostasis after EPH were collected to evaluate the outcome, complications, hospital stay of pregnant women, and to analyze the factors affecting the effect of pelvic packing. The cases included patients who were admitted to the Third Affiliated Hospital of Guangzhou Medical University after pelvic packing treatment in the other hospital due to continuous bleeding after EPH or who were referred to our hospital for pelvic packing treatment due to continuous bleeding after EPH from January 2014 to August 2021.Results:The median gestational week of 11 pregnant women was 38.3 weeks(38.0-39.9 weeks) , and the methods of termination of pregnancy were cesarean section in 7 cases (7/11) and vaginal delivery in 4 cases (4/11). The median time between postpartum hemorrhage and pelvic tamponade was 10 hours (5-57 hours), the median amount of bleeding was 8 500 ml(4 800-15 600 ml) , the median number of pelvic tamponade was 3 pieces (2-7 pieces), and the median retention time of gauze pad was 6.0 days (3.0-6.0 days). The median frequency of laparotomy in this pregnancy was 3 times (2-3 times), with a maximum of 4 among the 11 cases, the first pelvic packing was successful in hemostasis in 9 cases, and the final successful treatment in all of the 11 cases. All parturients had hemorrhagic shock (11/11) and disseminated intravascular coagulation (11/11) before pelvic packing. Other common complications were multiple organ dysfunction syndrome (9/11), cardiac arrest (4/11), deep vein thrombosis (3/11), septic shock (3/11), and intestinal obstruction (1/11). All parturients took out the gauze after the coagulation function returned to normal and there was no active bleeding. The recovery time of coagulation function in 11 cases was 3 days (3-5 days), the retention time of gauze pad was 6 days (3-6 days), the median length of stay in intensive care unit was 14 days (11-26 days), and the median total length of stay was 22 days (16-49 days).Conclusions:Pelvic packing could be used as a temporary strategy for intractable postpartum hemorrhage after EPH, which provides a key time for injury control resuscitation for patients with unstable vital signs. This technology provides an opportunity for referral to superior medical institutions and further treatment.

Phylogenetic and Mutation Points Analysis of Sophora japonica cv. jinhuai Based on DNA Barcoding Sequences / 中国实验方剂学杂志

ObjectiveTo conduct phylogenetic analysis of internal transcribed spacer 2 （ITS2） and chloroplast gene segments including psbA-trnH， rbcL， and matK of Sophora japonica cv. jinhuai resource samples from different geographical sources， and to explore the genetic diversity of S. japonica cv. jinhuai. MethodPolymerase chain reaction （PCR） method was used to amplify the nucleic acid sequences of ITS2， psbA-trnH， rbcL， and matK of S. japonica cv. jinhuai. Neighbor joining （NJ） method was used to construct phylogenetic trees， and Kimura 2-Parameter （K2P） model was used to calculate the genetic distance of different samples. MEGA and BIOEDIT softwares were applied for mutiple alignment and analysis of ITS2， psbA-trnH， rbcL， and matK sequences of S. japonica cv. jinhuai. ResultThe lengths of ITS2 sequence were 278-279 bp. The lengths of psbA-trnH were 289 bp. The lengths of rbcL sequence were 673 bp. The lengths of matK sequences were 786-792 bp. There were 3 mutation points in ITS2 and psbA-trnH， no mutation point in rbcL， and 13 mutation points in matK. The samples of S. japonica cv. jinhuai were clustered into two groups based on the phylogenetic tree constructed by ITS2 sequences. The sample of seedling tree in Baibao was clustered into one group， while the other 25 samples were clustered into another group. For the psbA-trnH sequence， the success rate of PCR amplification of 28 samples of S. japonica cv. jinhuai was 100%. The 28 samples of S. japonica cv. jinhuai were clustered into three groups based on the clustering results of psbA-trnH sequence. The sample of seedling tree in Shaoshui was clustered into one group. The five samples of grafting tree and seedling tree in Miaotou， grafting trees in Jiantang， Wenqiao， and Daxu， and seeding tree in Xianshui were clustered into one group. The other 21 samples were clustered into another group. The 26 samples of S. japonica cv. jinhuai were clustered into two groups based on the phylogenetic tree constructed by matK sequences. The sample of seedling tree in Xianshui was clustered into one group， while the other 25 samples were clustered into another group. The clustering results of the rbcL sequence of S. japonica cv. jinhuai could not distinguish 28 resource samples. The phylogenetic tree constructed by the combined sequence of ITS2+psbA-trnH+rbcL+matK divided S. japonica cv. jinhuai resource samples into 4 groups. The 13 samples of seedling trees in Qiyang， Daoxian， Miaotou， Shaoshui， Shitang， Xianshui， Jiantang， and Xiangli， and grafting trees in Qiyang， Miaotou， Yongsui， Wenqiao， and Yangtang were clustered into one group. The sample of seedling tree in Wenqiao was clustered into one group. The sample of seedling tree in Daxu was clustered into one group. The remaining samples were clustered into another group. ConclusionPhylogenetic and mutation analysis provide the theoretic foundation to investigate the evolution of the resources of S. japonica cv. jinhuai， and evaluate their genuineness. The results of mutation points can be used to identify the related S. japonica cv. jinhuai resources. The findings of this study show that the combination of different gene sequences has an optimal effect on plant identification.

NEXMIF mutations in intellectual disability and epilepsy: A report of 2 cases and literature review / 中南大学学报(医学版)

More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.

Correlation of fetal cervical cystic hygroma with chromosomal and structural abnormalities: analysis of 70 cases / 中华围产医学杂志

Objective:To analyze the correlation of fetal cervical cystic hygroma (CCH) with chromosomal and structural abnormalities and to assess the prognosis of CCH.Methods:This study retrospectively enrolled 70 fetuses with CCH diagnosed by prenatal ultrasound in the First Affiliated Hospital of Xi'an Jiao Tong University from July 2015, to December 2021. According to whether complicated by structural malformations or other anomalies, all the subjects were divided into the non-isolated and isolated CCH groups. The correlation of CCH and the gestational age at detection with chromosomal and structural abnormalities were analyzed and the prognosis of the cases were summarized using Chi-square test. Results:There were 34 isolated CCH (34/70, 49%) and 36 non-isolated CCH (36/70, 51%) among the 70 cases. In the non-isolated CCH group, there were eight cases (22%, 8/36) with abnormal heart structure, ten (28%, 10/36) with abnormal anterior abdominal wall, 16 (44%,16/36) with systemic edema and/or pleural effusion, one (3%,1/36) with craniocerebral abnormalities and one with holoprosencephaly and cardiac structural abnormalities. Eighteen out of 44 cases undergoing chromosome testing had chromosomal abnormalities, which were trisomy-18 ( n=6), trisomy-21 ( n=3), trisomy-13 ( n=3), 45,XO ( n=3), and chromosome segment duplication or deletion ( n=3). The detection rate of chromosome abnormality was higher in non-isolated CCH group comparing with isolated CCH group [59%(13/22) vs 23%(5/22), χ2=6.02, P=0.014]. There was no significant difference in the gestational age at the detection of CCH or proportion of women of advanced maternal age between the isolated and non-isolated CCH groups (both P>0.05). The ratios of isolated CCH cases with normal chromosome detected at the gestational weeks of 14-27 +6 was higher than those detected at 11-13 +6 weeks [62%(13/21) vs 17%(4/23), χ2=7.39, P=0.001]. Out of the 17 cases with isolated CCH and normal chromosomes, 12 were live births. One of the 12 cases still had a cystic mass with a diameter of 3 cm in the neck nine months after birth, and the other 11 cases had no mass at birth but one case died at the age of five months (hospitalized one week for neonatal edema),one case was found with anal atresia three days after birth and underwent operation and the remaining nine cases were normal during five months to six years follow-up. Conclusions:Non-isolated CCH is at a higher risk of chromosomal abnormalities. Isolated CCH cases detected later had higher rate of normal chromosome and often have a higher survival rate.

Effects of radical radiotherapy combined with different regimens of chemotherapy on radiation intestinal injury in patients with non-metastatic anal squamous cell carcinoma / 中华胃肠外科杂志

Objective: To investigate the effects of radical radiotherapy combined with different chemotherapy regimens (fluorouracil-based versus docetaxel plus cisplatin) on the incidence of radiation intestinal injury and the prognosis in patients with non-metastatic anal squamous cell carcinoma. Methods: A retrospective cohort study was conducted to recruit non-metastatic anal squamous cell carcinoma patients who underwent chemoradiotherapy in the Sixth Affiliated Hospital of Sun Yat-sen University and Nanfang Hospital from July 2013 to January 2021. Inclusion criteria: (1) newly diagnosed anal and perianal squamous cell carcinoma; (2) completed radical radiotherapy combined with concurrent chemotherapy; (3) tumor could be evaluated before radiotherapy. Exclusion criteria: (1) no imaging evaluation before treatment, or the tumor stage could not be determined; (2) patients undergoing local or radical resection before radiotherapy; (3) distant metastasis occurred before or during treatment; (4) recurrent anal squamous cell carcinoma. A total of 55 patients (48 from the Sixth Affiliated Hospital of Sun Yat-sen University and 7 from Nanfang Hospital) were given fluorouracil (the 5-FU group, n=34) or docetaxel combined with the cisplatin (the TP group, n=21). The evaluation of radiation intestinal injury, hematological toxicity and 3-year disease-free survival (DFS) rate were compared between the two groups. The effects of chemotherapy regimen and other clinicopathological factors on the incidence and severity of acute and chronic radiation intestinal injury were analyzed. The assessment of radiation intestinal injury was based on the American Cancer Radiotherapy Cooperation Group (RTOG) criteria. Results: During radiotherapy and within 3 months after radiotherapy, a total of 45 patients developed acute radiation intestinal injury, including 18 cases of grade 1 (32.7%), 22 cases of grade 2 (40.0%) and 5 cases of grade 3 (9.1%). No patient developed chronic radiation intestinal injury. Among the 34 patients in the 5-FU group, 21 had grade 2-3 radiation intestinal injury (21/34, 61.8%), which was significantly higher than that in the TP group (6/21, 28.6%) (χ(2)=5.723, P=0.017). Multivariate analysis showed that 5-FU chemotherapy regimen was an independent risk factor for radiation intestinal injury (HR=4.038, 95% CI: 1.250-13.045, P=0.020). With a median follow-up period of 26 (5-94) months, the 3-year DFS rate of patients in TP group and 5-FU group was 66.8% and 77.9%, respectively, whose difference was not significant (P=0.478). Univariate analysis showed that the DFS rate was associated with sex, age, tumor location, T stage, N stage, and induction chemotherapy (all P<0.05), while the DFS rate was not associated with chemotherapy regimen or radiation intestinal injury (both P>0.05). Multivariate analysis revealed that age ≥ 50 years old was an independent risk factor affecting the prognosis of patients (HR=8.301, 95% CI: 1.130-60.996, P=0.038). Conclusions: For patients with non-metastatic anal squamous cell carcinoma, radical radiotherapy combined with TP chemotherapy regimen can significantly reduce the incidence of radiation intestinal injury as compared to 5-FU regimen. However, due to the short follow-up time, the effect of different chemotherapy regimens on the prognosis is not yet clear.

Clinical analysis of 10 cases of hydatidiform mole with coexistent intrauterine pregnancy / 中华围产医学杂志

Objective:To investigate the diagnosis and management of partial or complete hydatidiform mole with coexistent intrauterine pregnancy.Methods:Clinical data of 10 cases of hydatidiform mole with coexistent intrauterine pregnancy admitted to the Third Affiliated Hospital of Guangzhou Medical University, from September 2009 to May 2019 were retrospectively described.Results:(1) During the same period, 65 960 women were delivered at our hospital, and hydatidiform mole with coexistent intrauterine pregnancy was accounted for 1/6 596, among which complete hydatidiform mole and coexisting fetus (CHMCF) and partial hydatidiform mole and coexistent fetus (PHMCF) were found in four and six cases, respectively. The mean age of the ten patients were (30.9±4.1) years old, ranging from 26 to 35 years old, with 2.5 (1-4) times of pregnancies. Nine cases were identified at 22 +3 (12 +3-32 +3) gestational weeks and one at 9 + weeks. (2) Recurrent vaginal bleeding during pregnancy occurred in six cases, nausea and vomiting in three cases, and hyperthyroidism in mid- and late pregnancy in two cases. One patient developed preeclampsia and one case of severe mitral regurgitation with mild pulmonary hypertension. (3) In the 10 patients, the summit serum β -hCG level was 139 935 (16 990-546 033) U/L, and CHMCF and PHMCF patients were 212 500 (200 000-546 033) U/L and 60 768 (16 990-225 000) U/L, respectively. (4) The ultrasound results revealed a dark honeycomb area of the placenta in five cases, placental thickening in two cases, and vesicular placenta in one case. One case was found with bilateral giant luteinized ovarian cyst by ultrasound, multiple metastases in the left lower lobe of the lung by chest CT, multiple nodules in the pleural wall of the left lung by lung MRI, and CHMCF by pelvic MRI. In one case, ultrasound at 14 weeks of gestation showed interrupted fetal abdominal wall, visible mass, gastric bubble, liver, part of the intestinal echoes, and omphalocele. One case was found with embryo arrest. (5) The karyotype analysis of one case through amniocentesis was 46,XX with no anomalies, and chromosome microarray analysis was arr[hg19](1-22)×2. Prenatal diagnosis was refused in the remaining cases. (6) Among the ten patients, three were terminated by rivanol intra-amniotic injection, two received drug abortion, and uterine evacuation, and two with spontaneous abortion followed by curettage with a visible fetus and hydatidiform tissue. Total hysterectomy was performed in one patient due to partial invasion of the uterus by hydatidiform mole. One patient underwent a cesarean section on account of the left lower lung metastasis. One case developed preeclampsia at 33 +4 weeks of gestation and delivered two premature infants by cesarean section. Pathology examination found a complete and partial vesicular fetal mass in four and six cases, with P57 (－) and P57 (+), respectively. (7) During the follow-up, two women developed the persistent trophoblastic disease and received chemotherapy, while the remaining eight cases did not. Conclusions:When hydatidiform mole with coexistent intrauterine pregnancy is found, a timely differential diagnosis between CHMCF and PHMCF is needed. CHMCF is at a higher risk of abortion, intrauterine death, premature delivery, preeclampsia, and other maternal complications. Therefore, termination of CHMCF should be individualized. Most PHMCF patients have fetal malformation or fetal loss; thereby, timely termination is recommended.

Compound heterozygous mutations in POLR3A gene cause global developmental delay with epilepsy and striatal degeneration / 中华神经科杂志

Objective:To investigate the clinical, imaging and genetic features of patients with global developmental delay combined with epilepsy and striatal degeneration caused by POLR3A gene mutations.Methods:A total of three patients from two families with non-consanguineous marriages admitted to the Department of Pediatric Neurology of Xiangya Hospital of Central South University in 2020 were examined in detail. Peripheral blood DNA was extracted, and whole-exome sequencing was performed on the patients, combined with Sanger sequencing for verification. The mutation and protein function predictor softwares were applied to analyze the mutation sites.Results:All three patients presented with global developmental delay, seizures, dystonia. Head magnetic resonance imaging of all patients suggested basal ganglia atrophy and striatal degeneration. All had compound heterozygous mutations of c.1980 G>C; c.1771-6 C>G and c.2044C>T; c.1771-7 C>G in POLR3A gene as indicated by whole-exome sequencing. Sanger sequencing validation confirmed that the compound heterozygous mutations were originated from the parents of probands from the two families, respectively. Bioinformatic analysis suggested pathogenic features of the mutations.Conclusions:Compound heterozygous mutations in POLR3A gene , including a splice site mutation result in global developmental delay combined with epilepsy, striatal degeneration. Clinicians should promote the awareness of POLR3 related spectrum disorders, thus make early recognition and diagnosis.

Effects of problem-solving therapy on breastfeeding self-efficacy and psychological status among primiparas / 中国实用护理杂志

Objective:To explore the effects of problem-solving therapy on breastfeeding self-efficacy and psychological status among primiparas, to provide basis for improving the breastfeeding of primipara.Methods:A total of 102 primiparas were divided into experimental group and control group by random number table method, each group contained 51 cases. Finally, 47 cases in the experimental group and 49 cases in the control group completed the study. The control group received routine nursing, while primiparas in the experimental group carried out problem-solving therapy. Before and after 6-week intervention, the effects was assessed by Breastfeeding Self-Efficacy Scale (BSES), Edinburgh Postnatal Depression Scale (EPDS) and General Well-being Schedule (GWB), respectively.Results:After intervention, the scores of primapara feedig cognition, feeding feeling, feeding skills and BSES total scores were (21.13±2.97) points, (65.47±6.63) points, (31.94±2.59) points, (118.53±8.47) points in the experimental group, significantly higher than (19.43±3.28) points, (61.76±5.20) points, (30.53±2.01) points, (111.71±6.11) points in the control group ( t values were 2.658-4.507, P<0.01); the scores of EPDS were (6.04±1.49) points in the experimental group, significantly lower than (6.92±2.08) points in the control group; the scores of life satisfaction and interest, depression and pleasure, energy, relaxation and tension in General Well-Being (GWB) and total scores were (7.51±1.71) points, (20.19±2.47) points, (21.68±2.32) points, (17.06±2.74) points, (90.45±4.96) points in the experimental group, significanlty higher than (6.41±1.82) points, (18.71±2.98) points, (20.57±1.87) points, (15.78±1.79) points, (84.61±5.26) points in the control group, the difference was statistically significant ( t values were 2.380-5.587, P<0.05 or 0.01). Conclusion:Problem-solving therapy can improve breastfeeding self-efficacy and alleviate postnatal depression as well as enhance subjective well-being of primipara women.