Application progress of Ilizarov technique in orthopedics / 中国基层医药

Ilizarov technique is designed based on the "tension-stress principle". Application of the Ilizarov technique can help form a stable mechanical structure through external fixation. It only creates small wounds, without peeling off the surrounding tissue and periosteum. It connects different types of fixation pins and bone or soft tissue to form a traction force, which continuously stimulates the regeneration of bone and tissue and improves the local blood supply and early functional rehabilitation exercises, forming a complete set of minimally invasive orthopedic treatment systems. Ilizarov technique has achieved good results in fracture healing, deformity correction, tissue repair, osteomyelitis, bone nonunion, bone defect, and bone tumor. This paper will summarize the clinical application and research of the Ilizarov technique in orthopedics and explore the key problems of the Ilizarov technique that need to be solved at present.

Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor drugs for the treatment of wet age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical efficacy of Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor(VEGF)in the treatment of wet age-related macular degeneration(wARMD).METHODS: A total of 58 patients(58 eyes)with wARMD who were treated in Ningbo Eye Hospital from September 2020 to November 2022 were collected. They were divided into two groups according to randomized digital table: 29 patients(29 eyes)for the combination group and the other 29 patients(29 eyes)for the injection group. The injection group was only given intravitreal injection of conbercept; the combination group was orally administrated with Yishen Yanggan Mingmu formula combined with intravitreal injection of conbercept. The best corrected visual acuity(BCVA), central macular thickness(CMT)and the improvement of traditional Chinese medicine(TCM)syndromes after 3mo of treatment were observed and the clinical efficacy was evaluated.RESULTS: After 3mo of treatment, the total improved effective rate of the combination group(76%)was higher than the rate of the injection group(66%). After the treatment, the BCVA of the two groups was both higher than that before treatment(P<0.05), the CMT in both groups was lower than that before the treatment(P<0.05), and the improvement of CMT of the combination group was better than the injection group(-155.93±143.79μm vs. -95.36±56.81μm, P<0.05). After 3mo of treatment, each kinds of TCM syndrome in the combination group were significantly improved compared with those syndromes before the treatment(P<0.001). In the injection group, only blurred vision was improved(P<0.05). After the treatment, the scores of dizziness and insomnia, soreness and weakness of waist and knees, paleness and cold limbs, dry eyes and fatigue in the combination group were significantly lower than the injection group(P<0.001).CONCLUSIONS: The Yishen Yanggan Mingmu formula combined with intravitreal anti-VEGF drug injection is effective in the treatment of wARMD.

Deubiquitinating enzyme MINDY1 is an independent risk factor for the maintenance of stemness and poor prognosis in liver cancer cells / 中华肝脏病杂志

Objective: To explore the key deubiquitinating enzymes that maintain the stemness of liver cancer stem cells and provide new ideas for targeted liver cancer therapy. Methods: The high-throughput CRISPR screening technology was used to screen the deubiquitinating enzymes that maintain the stemness of liver cancer stem cells. RT-qPCR and Western blot were used to analyze gene expression levels. Stemness of liver cancer cells was detected by spheroid-formation and soft agar colony formation assays. Tumor growth in nude mice was detected by subcutaneous tumor-bearing experiments. Bioinformatics and clinical samples were examined for the clinical significance of target genes. Results: MINDY1 was highly expressed in liver cancer stem cells. The expression of stem markers, the self-renewal ability of cells, and the growth of transplanted tumors were significantly reduced and inhibited after knocking out MINDY1, and its mechanism of action may be related to the regulation of the Wnt signaling pathway. The expression level of MINDY1 was higher in liver cancer tissues than that in adjacent tumors, which was closely related to tumor progression, and its high expression was an independent risk factor for a poor prognosis of liver cancer. Conclusion: The deubiquitinating enzyme MINDY1 promotes stemness in liver cancer cells and is one of the independent predictors of poor prognosis in liver cancer.

Phenotypic and genetic analysis of a Chinese pedigree affected with Oral-facial-digital syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic basis for a Chinese pedigree affected with Oral-facial-digital syndrome type I (OFD1).@*METHODS@#A pedigree with OFD1 who presented at Hebei General Hospital on March 17, 2021 was selected as the subject. Clinical data of the child was collected. Trio-whole exome sequencing (trio-WES) was carried out for the proband and members of her pedigree, and candidate variant was verified by Sanger sequencing.@*RESULTS@#The proband has featured hypotelorism, broad nasal root, flat nasal tip, lobulated tongue, tongue neoplasia, camptodactyly of left fifth finger, syndactyly of right fourth and fifth fingers, and delayed intellectual and language development. Trio-WES revealed that the proband and her daughter, sister and mother have harbored a heterozygous c.224A>G (p.Asn75Ser) variant of the OFD1 gene. The same variant was not found among healthy members from her pedigree.@*CONCLUSION@#The c.224A>G (p.Asn75Ser) variant probably underlay the OFD1 in this pedigree. Above discovery has enriched the spectrum of OFD1 gene variants.

Clinical features and long-term prognosis of diabetic patients with low or intermediate complexity coronary artery disease post percutaneous coronary intervention / 中华心血管病杂志

Objective: To investigate the clinical features and long-term prognostic factors of diabetic patients with low or intermediate complexity coronary artery disease (CAD) post percutaneous coronary intervention (PCI). Methods: This was a prospective, single-centre observational study. Consecutive diabetic patients with SYNTAX score (SS)≤32 undergoing PCI between January and December 2013 in Fuwai hospital were included in this analysis. The patients were divided into two groups based on SS, namely SS≤22 group and SS 23-32 group. Multivariate Cox regression analysis was performed to identify independent factors related to poor 5-year prognosis. The primary outcomes were cardiac death and recurrent myocardial infarction, the secondary outcomes were all cause death and revascularization. Results: Of the 3 899 patients included in the study, 2 888 were men (74.1%); mean age was 59.4±9.8 years. There were 3 450 patients in the SS≤22 group and 449 patients in the SS 23-32 group. Compared with SS≤22 group, the incidence of revascularization was higher in SS 23-32 group (18.9% (85/449) vs. 15.2% (524/3450), log-rank P=0.019). There was no significant difference in all-cause death, cardiac death and recurrent myocardial infarction between the two groups (log-rank P>0.05). Multivariate Cox regression analysis showed that age (HR=1.05, 95%CI 1.02-1.08, P<0.001), chronic obstructive pulmonary disease (HR=3.12, 95%CI 1.37-7.07, P=0.007) and creatinine clearance rate (CCr)<60 ml/min (HR=3.67, 95%CI 2.05-6.58, P<0.001) were independent risk factors for 5-year cardiac death, while left ventricular ejection fraction (HR=0.94, 95%CI 0.91-0.96, P<0.001) was a protective factor. Previous PCI (HR=2.04, 95%CI 1.38-3.00, P<0.001), blood glucose level≥11.1 mmol/L on admission (HR=2.49, 95%CI 1.32-4.70, P=0.005) and CCr<60 ml/min (HR=1.85, 95%CI 1.14-2.99, P=0.012) were independent risk factors for 5-year recurrent myocardial infarction. The SS of 23-32 was independently associated with risk of revascularization (HR=1.54, 95%CI 1.09-2.16, P=0.014), after adjusting for residual SS. Residual SS was not a risk factor for 5-year prognosis. Conclusions: In diabetic patients with low-or intermediate complexity CAD, SS 23-32 is associated with increased risk of 5-year revascularization; the clinical characteristics of the patients are associated with the long-term mortality and recurrent myocardial infarction, but not related to revascularization.

Surveillance of the progression and assessment of treatment endpoints for nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is an aggressive form of nonalcoholic fatty liver disease (NAFLD) characterized by steatosis-associated inflammation and liver injury. Without effective treatment or management, NASH can have life-threatening outcomes. Evaluation and identification of NASH patients at risk for adverse outcomes are therefore important. Key issues in screening NASH patients are the assessment of advanced fibrosis, differentiation of NASH from simple steatosis, and monitoring of dynamic changes during follow-up and treatment. Currently, NASH staging and evaluation of the effectiveness for drugs still rely on pathological diagnosis, despite sample error issues and the subjectivity associated with liver biopsy. Optimizing the pathological assessment of liver biopsy samples and developing noninvasive surrogate methods for accessible, accurate, and safe evaluation are therefore critical. Although noninvasive methods including elastography, serum soluble biomarkers, and combined models have been implemented in the last decade, noninvasive diagnostic measurements are not widely applied in clinical practice. More work remains to be done in establishing cost-effective strategies both for screening for at-risk NASH patients and identifying changes in disease severity. In this review, we summarize the current state of noninvasive methods for detecting steatosis, steatohepatitis, and fibrosis in patients with NASH, and discuss noninvasive assessments for screening at-risk patients with a focus on the characteristics that should be monitored at follow-up.

Clinical feature and genetic analysis of a patient with Idiopathic hypogonadotropic hypogonadism due to a novel variant of CHD7 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical feature and genetic etiology of a patient with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) due to variant of CHD7 gene.@*METHODS@#A patient who had presented at Anhui Provincial Children's Hospital in October 2022 was selected as the study subject. Clinical data of the patient was collected. The patient and his parents were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The patient had featured delayed development of secondary sexual characteristics but normal olfactory function. Genetic testing revealed that he has harbored a c.3052C>T (p.Pro1018Ser) missense variant of the CHD7 gene, for which both of his parents were of the wild type. The variant has not been recorded in the PubMed and HGMD databases. Analysis of amino acid sequences suggested that the variant site is highly conserved, and the variant may affect the stability of protein structure. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.3032C>T variant was classified as a likely pathogenic (PS2+PM2_Supporting+PP2+PP3+PP4).@*CONCLUSION@#The delayed development of secondary sexual characteristics of the patient may be attributed to the c.3052C>T (p.Pro1018Ser) variant of the CHD7 gene. Above finding has expanded the variation spectrum of the CHD7 gene.

Engineering the plastic degradation enzyme Ple629 from marine consortium to improve its thermal stability / 生物工程学报

Petrochemical-derived polyester plastics such as polyethylene terephthalate (PET) and polybutylene adipate terephthalate (PBAT) have been widely used. However, the difficulty to be degraded in nature (PET) or the long biodegradation cycle (PBAT) resulted in serious environmental pollution. In this connection, treating these plastic wastes properly becomes one of the challenges of environment protection. From the perspective of circular economy, biologically depolymerizing the waste of polyester plastics and reusing the depolymerized products is one of the most promising directions. Recent years have seen many reports on polyester plastics degrading organisms and enzymes. Highly efficient degrading enzymes, especially those with better thermal stability, will be conducive to their application. The mesophilic plastic-degrading enzyme Ple629 from the marine microbial metagenome is capable of degrading PET and PBAT at room temperature, but it cannot tolerate high temperature, which hampers its potential application. On the basis of the three-dimensional structure of Ple629 obtained from our previous study, we identified some sites which might be important for its thermal stability by structural comparison and mutation energy analysis. We carried out transformation design, and performed expression, purification and thermal stability determination of the mutants. The melting temperature (Tm) values of mutants V80C and D226C/S281C were increased by 5.2 ℃ and 6.9 ℃, respectively, and the activity of mutant D226C/S281C was also increased by 1.5 times compared with that of the wild-type enzyme. These results provide useful information for future engineering and application of Ple629 in polyester plastic degradation.

Expression, purification and characterization of a novel bis (hydroxyethyl) terephthalate hydrolase from Hydrogenobacter thermophilus / 生物工程学报

PET (polyethylene terephthalate) is one of the most important petrochemicals that is widely used in mineral water bottles, food and beverage packaging and textile industry. Because of its stability under environmental conditions, the massive amount of PET wastes caused serious environmental pollution. The use of enzymes to depolymerize PET wastes and upcycling is one of the important directions for plastics pollution control, among which the key is the depolymerization efficiency of PET by PET hydrolase. BHET (bis(hydroxyethyl) terephthalate) is the main intermediate of PET hydrolysis, its accumulation can hinder the degradation efficiency of PET hydrolase significantly, and the synergistic use of PET hydrolase and BHET hydrolase can improve the PET hydrolysis efficiency. In this study, a dienolactone hydrolase from Hydrogenobacter thermophilus which can degrade BHET (HtBHETase) was identified. After heterologous expression in Escherichia coli and purification, the enzymatic properties of HtBHETase were studied. HtBHETase shows higher catalytic activity towards esters with short carbon chains such as p-nitrophenol acetate. The optimal pH and temperature of the reaction with BHET were 5.0 and 55 ℃, respectively. HtBHETase exhibited excellent thermostability, and retained over 80% residual activity after treatment at 80 ℃ for 1 hour. These results indicate that HtBHETase has potential in biological PET depolymerization, which may facilitate the enzymatic degradation of PET.

Prediction of Lymph Node Metastasis of Mixed Ground-glass Nodules Based on Clinical Imaging Information / 中国肺癌杂志

BACKGROUND@#Previous studies have shown that lymph node metastasis only occurs in some mixed ground-glass nodules (mGGNs) which the pathological results were invasive adenocarcinoma (IAC). However, the presence of lymph node metastasis leads to the upgrading of tumor-node-metastasis (TNM) stage and worse prognosis of the patients, so it is important to perform the necessary evaluation before surgery to guide the operation method of lymph node. The aim of this study was to find suitable clinical and radiological indicators to distinguish whether mGGNs with pathology as IAC is accompanied by lymph node metastasis, and to construct a prediction model for lymph node metastasis.@*METHODS@#From January 2014 to October 2019, the patients with resected IAC appearing as mGGNs in computed tomography (CT) scan were reviewed. All the lesions were divided into two groups (with lymph node metastasis or not) according to their lymph node status. Lasso regression model analysis by applying R software was used to evaluate the relationship between clinical and radiological parameters and lymph node metastasis of mGGNs.@*RESULTS@#A total of 883 mGGNs patients were enroled in this study, among which, 12 (1.36%) showed lymph node metastasis. Lasso regression model analysis of clinical imaging information in mGGNs with lymph node metastasis showed that previous history of malignancy, mean density, mean density of solid components, burr sign and percentage of solid components were informative. Prediction model for lymph node metastasis in mGGNs was developed based on the results of Lasso regression model with area under curve=0.899.@*CONCLUSIONS@#Clinical information combined with CT imaging information can predict lymph node metastasis in mGGNs.

Aspiration risk of preventive placement of nasal jejunum nutrition tube in advanced esophageal cancer patients receiving radiotherapy and the influencing factors / 肿瘤研究与临床

Objective:To investigate the aspiration risk of preventive placement of nasal jejunum nutrition tube in advanced esophageal cancer patients receiving radiotherapy and the influencing factors.Methods:The clinical data of 220 patients with advanced esophageal cancer who received radiotherapy and preventive placement of nasal jejunum nutrition tube feeding from November 2020 to November 2021 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. The level of aspiration risk was measured according to the standard swallowing function assessment scale (SSA). The questionnaire collected the following data: (1) the general data including gender, age, educational level, history of smoking, history of alcoholism, knowledge of aspiration; (2) the disease factors including tumor staging, tumor site, swallowing function, abdominal distention; (3) the nosocomial factors including history of esophageal cancer surgery, sedation and analgesia treatment, combination of chemotherapy or not, cumulative radiotherapy dose, grade of radiation esophagitis, the position, time and tube feeding method of enteral nutrition. The standard swallowing function of patients was measured and repeated saliva swallowing test (RSST) was used to screen the patients with the difficulty in the esophageal function swallowing. Multiple linear regression was used to analyze the factors affecting aspiration risk.Results:A total of 220 patients with advanced esophageal cancer were enrolled in the investigation. Finally, 70 patients (31.8%) had grade 0 aspiration risk, and SSA score was 19; 23 patients (10.5%) had grade I aspiration risk, and SSA score was (23.4±1.3); 103 patients (46.8%) had grade Ⅱ aspiration risk, and SSA score was (27.5±1.1); 24 patients (10.9%) had grade Ⅲ aspiration risk, and SSA score was (33.2±1.5); 136 patients (61.8%) in total had aspiration risk. There were 32.7% (72/220) patients knowing the knowledge of aspiration. Multifactor analysis showed that esophageal tumor site ( t = -2.869, P = 0.005), cumulative radiotherapy dose ( t = 5.558, P < 0.001), grade of radiation esophagitis ( t = 11.405, P < 0.001), the duration time of enteral nutrition ( t = 4.050, P < 0.001) were independent factors affecting the aspiration risk. Conclusions:The aspiration risk of preventive placement of nasal jejunum nutrition tube in advanced esophageal cancer patients receiving radiotherapy is high, which is related to esophageal tumor site, grade of radiation esophagitis, cumulative radiotherapy dose and the duration time of enteral nutrition.

Ultrashortwave therapy can inhibit inflammation and promote recovery from spinal cord injury / 中华物理医学与康复杂志

Objective:To observe any effect of ultrashortwave (USW) therapy on inflammatory cytokines and the MAPK pathway of rats with a spinal cord injury.Methods:Seventy-nine Sprague-Dawley rats were randomly divided into a control group ( n=35), an intervention group ( n=35) and a sham group ( n=9). Allen′s method was used to establish a contusion model of SCI in the rats of the control and intervention groups, while the sham group′s spinal tissues were exposed but not stricken. Beginning twenty-four hours after SCI modeling, the intervention group was given 7min of USW therapy daily, five days a week till the day of sacrifice for sampling the target area of spinal cord for tests. Then, motion function was evaluated using Basso, Beattie and Bresnahan (BBB) scoring. One, three and seven days after the SCI modeling, immunofluorescence and western blotting were employed to observe any changes in inflammatory factors and the MAPK pathway in the lesioned area. Results:Fourteen days after the modeling the average BBB score of the intervention group was significantly higher than the control group′s average. Moreover, 7 days after the modeling the average content of the domains containing protein 3 (NLRP3), interleukin-6 (IL-6), IL-6 receptor and tumor necrosis factor-α (TNF-α) in the target area of the spinal cord of sham group showed significantly lower levels than in the other 2 groups. And the levels in the intervention group were significantly lower than in the control group. Seven days after the modeling the number of cells positive for zinc finger protein 36 (TTP) in the lesioned area of the intervention group was significantly greater than among the control group. At the same time the levels of MAPK-activated protein kinase 2 (MK2), phosphorylated-mitogen-activated protein kinase-activated version (p-MK2) and TTP in the control and intervention groups were significantly higher than in the sham group. And there were significant differences between the intervention group and control group in the levels of MK2, p-MK2 and TTP.Conclusion:Ultrashortwave therapy can inhibit inflammation by regulating the MAPK inflammatory pathway, promoting the recovery of motion functions, at least in rats.

Genetic analysis of a pedigree of DYNC2H1 gene variation-caused short rib polydactyly syndrome type Ⅲ / 中华围产医学杂志

This paper reported the genetic analysis of a pedigree in which three affected fetuses with short limbs were revealed by first-trimester ultrasonography in three consecutive pregnancies. Tissues of the second aborted fetus were collected and analyzed by chromosome karyotype analysis and whole exome sequencing. The results indicated compound heterozygous mutations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene. Real-time fluorescence quantitative polymerase chain reaction and Sanger sequencing further confirmed that the two variants were inherited from the father and the mother with normal phenotypes, respectively. EX64-EX83 Del was a likely pathogenic variant and c.8190G>T was a variant of uncertain significance. Based on the above results and the medical history, it was highly suspected that the fetus had autosomal recessive short rib polydactyly syndrome type Ⅲ caused by compound heterozygous variants. Real-time fluorescent quantitative polymerase chain reaction and Sanger sequencing results of the third aborted fetus were consistent with the second fetus. Given the same phenotypes of fetuses in the second and third pregnancy, it was strongly suggested that the heterozygous variations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene were the pathogenic variants in this pedigree.

Risk factors of hepatic artery injury during percutaneous transhepatic biliary drainage / 中华普通外科杂志

Objective:To investigate the incidence and risk factors of hepatic artery injury during percutaneous transhepatic biliary drainage (PTBD).Methods:From Apr 2002 to Dec 2020, the clinical data of 1 446 patients undergoing PTBD were retrospectively analyzed.Results:Hepatic artery injury occurred in 7 cases, with an incidence of 0.48%. Fluoroscopy guided puncture was used in all cases. In those 7 cases (0.48%) a drainage catheter was failed to put in place after multiple attempts, hepatic artery injury occurred in 1 case; One drainage catheter was inserted in 1 314 cases (90.87%), hepatic artery injury occurred in 5 cases; One hundred and twenty-five cases (8.65%) were implanted with two drainage catheter, and 1 case had hepatic artery injury. Failure to successfully insert the drainage catheter increase the incidence of hepatic artery injury ( OR=0.06,95% CI 0.01-0.71, P=0.026) .There were 1 430 cases (98.89%) with oblique needle tip and 5 cases had hepatic artery injury; There were 16 cases (1.11%) with triangular needle tip and 2 cases had hepatic artery injury. Triangular needle tip increased the incidence of hepatic artery injury( OR=55.57, 95% CI 6.84-451.38, P<0.001). Conclusion:Hepatic artery injury is a rare complication of PTBD.The use of triangular needle and the failure of drainage were the risk factors of hepatic artery injury.

Application value of modified Overlap esophagogastric tube reconstruction in totally laparos-copic radical proximal gastrectomy / 中华消化外科杂志

Objective:To investigate the application value of modified Overlap esophago-gastric tube (MO-EG) reconstruction in totally laparoscopic radical proximal gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 7 patients with upper gastric cancer or adenocarcinoma of esophagogastric junction (AEG) who underwent totally laparoscopic radical proximal gastrectomy with MO-EG reconstruction in the Second Hospital of Jilin University from January 2019 to December 2020 were collected. There were 4 males and 3 females, aged 62(range, 55-72)years. The body mass index of the 7 patients was 21.5(range, 18.5-26.0)kg/m 2. Of the 7 patients, 2 cases had early upper third gastric cancer and 5 cases had Siewert Ⅱ AEG. All patients underwent totally laparoscopic radical proximal gastrectomy with MO-EG recons-truction using barbed sutures. Observation indicators: (1) surgical situations; (2) postoperative recovery situations; (3) postoperative histopathological examinations; (4) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect postoperative esophageal reflux, endoscopic classification of esophageal reflux, anastomotic complications, tumor recurrence and metastasis and survival of patients up to December 2021. Measurement data with normal distribution were represented as Mean±SD and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All the 7 patients underwent totally laparoscopic radical proximal gastrectomy and D 1+ lymph node dissection with MO-EG reconstruction through abdominal transhiatal approach. None of the 7 patients underwent conversion to open surgery or additional thoracotomy. The operation time, time of digestive reconstruction, volume of intraoperative blood loss and length of esophagus dissected of 7 patients were (271±36)minutes, (44±10)minutes, (53±26)mL and (6.4±0.3)cm, respec-tively. (2) Postoperative recovery situations. The time to postoperative initial out-of-bed activities, time to postoperative first flatus, time to postoperative initial liquid food intake and duration of hospital stay of 7 patients were (21±5)hours, (2.9±0.9)days, (5.0±0.7)days and (10.1±1.9)days, respectively. None of the 7 patients had postoperative severe complications such as bleeding, anasto-motic leakage or mortality. One patient had postoperative pulmonary infection and recovered after anti-infection treatment. Two patients had pleural effusion and were improved after conserva-tive treatment. (3) Postoperative histopathological examinations. The tumor diameter of 7 patients was (2.5±0.7)cm. Histopathological examination of upper margins of 7 patients was negative. The distance between the esophagus margin and the superior margin of the tumor of patients with AEG was (1.8±0.6)cm. The number of lymph node dissected and the number of inferior mediastinum lymph node dissected of 7 patients were 26.0±3.6 and 3.7±1.1, respectively. Pathological TNM stages of 7 patients were 2 cases of stage ⅠB, 4 cases of ⅡA, 1 case of ⅡB. (4) Follow-up. All the 7 patients were followed up for 18(range, 12?36)months. Of the 7 patients, 4 cases reported asymptomatic, 2 cases had symptoms of reflux and 1 case had chocked feeling after eating. All the 7 patients underwent barium meal examination of gastrointestinal tract without anastomotic dysfunction or anastomotic stenosis. Six of the 7 patients underwent gastroscopy at postoperative 1 year and only 1 of them reported grade B reflux esophagitis according to Los Angeles classification, while the rest of 5 patients had no evidence of obvious reflux. None of the 7 patients had postoperative gastric cancer tumor recurrence, metastasis or death. Conclusion:Application of MO-EG reconstruction in totally laparoscopic radical proximal gastrectomy is safe and feasible, with satisfactory short-term effects.

Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

Clinical characteristics and genetic analysis of an ethnic Han Chinese child with Keppen-Lubinsky syndrome due to a de novo KCNJ6 mutation / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical characteristics and genetic basis for a child with Keppen-Lubinsky syndrome (KPLBS).@*METHODS@#Trio-whole exome sequencing (Trio-WES) was carried out for the proband and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child has featured peculiar facies including large eyes, alar hypoplasia, microretrognathia, premature aging appearance in addition with growth delay and mental retardation. Trio-WES has identified that she has carried a de novo variant of the KCNJ6 gene, namely c.460G>C (p.Gly154Arg). The variant has not been recorded in the database. Prediction of protein structure indicated that the variant may affect the potassium ion selective filtration structure channel in the transmembrane region of KCNJ6 protein, which may result in up regulation of the function of the channel.@*CONCLUSION@#The de novo c.460G>C (p.Gly154Arg) variant of the KCNJ6 gene probably underlay the KPLBS in this child. Above finding has enriched the genotypic and phenotype spectrum of this syndrome.

Effect of dietary intake before fasting on physiological distribution of 18F-FDG PET/CT imaging / 中华核医学与分子影像杂志

Objective:To explore the effect of dietary intake before fasting on the physiological distribution of 18F-FDG PET/CT, and to improve the 18F-FDG PET/CT image quality. Methods:From August 2019 to May 2020, questionnaire of dietary intake before fasting of 118 patients (73 males, 45 females; age (58.4±13.4) years) who performed PET/CT imaging in Zhongshan Hospital, Fudan University were retrospectively analyzed. The total dietary energy intake, the nutrient intake and energy supply ratio of the three energy source nutrients, the type of raw materials and the texture of diet were included. The SUV max and SUV mean of the liver, mediastinal blood pool and hip muscles were measured. Single-factor and multi-factors linear regression analyses were used to analyze data. Results:The fasting blood glucose of 118 subjects was (5.36±1.01) mmol/L. The texture of diet before fasting were general diet, semiliquid diet and liquid diet, which were 42 (35.59%), 72 (61.02%) and 4 (3.39%) subjects, respectively. The energy supply ratios of carbohydrate, protein and fat were (55.46±18.27)%, (16.70±7.38)% and (27.72±14.53)%, respectively. The results of multi-factors regression analysis indicted that protein energy ratio was an independent factor influencing SUV max ( β=0.005, P=0.031) and SUV mean ( β=0.003, P=0.042) of the hip muscles, and the texture of diet was an independent factor influencing SUV max ( β=0.126, P=0.030) and SUV mean ( β=0.197, P=0.002) of mediastinal blood pool. Conclusions:The dietary intake before fasting has significant effect on the imaging quality of 18F-FDG. The protein energy ratio is an independent factor influencing SUV max and SUV mean of the hip muscles. The texture of diet is an independent factor influencing SUV max and SUV mean of mediastinal blood pool.

Retrospective analysis for 424 330 first-line screening results of non-invasive prenatal testing in Hebei province / 中华妇产科杂志

Objective:To evaluate the effect of noninvasive prenatal testing (NIPT) as first-line screening in fetal chromosome aneuploidy screening practice, and to provide evidence for the prevention and control strategy of birth defects.Methods:Since July 2019, Hebei province had carried out the NIPT project providing first-line screening for eligible pregnant women in the area (except for those who were not applicable). Pregnant women with high risk received genetic counseling, prenatal diagnosis and intervention guidance. Low risk and false-positive ones received continuous detection and moved to prenatal diagnosis center for counseling and diagnosis if abnormities were discovered. All pregnant women were followed up to learn about pregnancy outcomes and newborn health status. Detection results and clinical data of pregnant women participating the NIPT project from July 2019 to July 2020 were collected. The detection results and effect of NIPT were analyzed.Results:(1) Basic information of the screened population: A total of 424 330 pregnant women were screened, and 423 596 were successfully detected, with a success rate of 99.83% (423 596/424 330). The age of pregnant women was (28.8±4.5) years old; the gestational age of screening was (16.6±2.3) weeks; the proportion of advanced-age pregnant women (≥35 years old) was 10.18% (43 132/423 596); in vitro fertilization-embryo transfer (IVF-ET) rate was 1.58% (6 713/423 596); the twin rate was 1.38% (5 849/423 596); the proportion of primipara was 34.23% (144 977/423 596). (2) Screening results and detection performance: totally, 325, 73 and 20 pregnant women were diagnosed with trisomy 21, 18 and 13; the sensitivity were 99.39%, 100.00% and 100.00%; the specificity were 99.98%, 99.99% and 99.98%; the positive predictive value were 75.76%, 68.87% and 21.51%, respectively. Besides, 249 190 pregnant women were received supplementary reports as well, and 255, 10 and 9 were confirmed for sex chromosome aneuploidy, other autosomal aneuploidy and deletion/duplication syndrome; the positive predictive value were 37.78%, 6.06% and 32.14%, respectively. The sensitivity of NIPT for target trisomy (trisomy 21, 18 and 13) screening in advanced-age, IVF-ET and twin pregnant women were 99.29%, 100.00% and 90.00%, respectively; the specificity were 99.93% for all; the positive predictive value were 82.25%, 61.54% and 69.23%, respectively.Conclusions:NIPT has a significant effect and good performance in the first-line screening of fetal chromosome aneuploidy in the whole population, which might provide reference for the improvement of birth defect prevention and control strategy.

Physical activity, sedentary behavior and associations with built environment for children and adolescents / 中国学校卫生

Abstract@#Physical inactivity and prolonged sedentary time are currently important health issues for children and adolescents. More evidences are required in the field of physical activity and sedentary behavior among children and adolescents. Therefore, it is necessary to summarize and review the relevant research progress regarding health implications of physical inactivity and sedentary behavior,and possible role of built environment. With the ultimate goal of health promotion for children and adolescents, the priority strategy might focus on increasing physical activity and reducing sedentary behavior through modifying the built environment.