Application of continuous renal replacement therapy combined with extracorporeal carbon dioxide removal in children with acute respiratory failure / 中华急诊医学杂志

Objective:To explore the role of continuous renal replacement therapy (CRRT) combined with extracorporeal carbon dioxide removal (ECCO 2R) in the treatment of children with respiratory failure. Methods:The clinical data of 12 children with respiratory failure who were treated with CRRT+ECCO 2R in PICU of Jinan Children's Hospital from July 2020 to August 2022 were collected and analyzed retrospectively. The outcomes and the external pipeline usage of the patients were observed, and the blood gas analysis and ventilator parameters before 1 h and after 1, 6, 12 and 24 h of the treatment were compared by one-way ANOVA with LSD post hoc correction. Results:Six patients successfully withdrew from CRRT+ECCO 2R and mechanical ventilation, three patients were transferred to ECMO treatment. Three cases died after voluntary withdrawal of treatment, and two cases died due to treatment failure. The mortality rate was 41.7%. After continuous treatment of CRRT+ECCO 2R for 15 to 112 h, two cases experienced extracorporeal circuit obstruction. After 1 h of treatment, PaCO 2 decreased from (64.67±24.4) mmHg to (49.42±15.54) mmHg, pH increased from (7.28±0.20) to (7.38±0.11), FiO 2 decreased from (0.85±0.13) to (0.78±0.15), PC decreased from (19.42±4.34) cmH 2O to (17.75±4.00) cmH 2O. After 24 h of treatment, PaCO 2 decreased to (39.2±5.55) mmHg, pH increased to (7.41±0.04), FiO 2 decreased to (0.46±0.11), and PC decreased to (13.8±3.36) cmH 2O, and the differences were statistically significant compared with before treatment ( P < 0.05). Conclusions:The combination of CRRT and ECCO 2R therapy can safely substitute for partial lung ventilation/perfusion function, and play a role in protecting right heart function and improving lung-kidney interaction. It can be considered as an option for extracorporeal respiratory, circulatory, and renal support, and consequently has broad prospects.

Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis.@*METHODS@#A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared.@*RESULTS@#The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively.@*CONCLUSION@#Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Effect of duodenal stump reinforcement on postoperative complications in patients undergoing laparoscopic radical gastrectomy / 中华胃肠外科杂志

Objective: To evaluate the influence of duodenal stump reinforcing on the short-term complications after laparoscopic radical gastrectomy. Methods: A retrospective cohort study with propensity score matching (PSM) was conducted. Clinical data of 1204 patients with gastric cancer who underwent laparoscopic radical gastrectomy at the First Affiliated Hospital of Army Medical University from April 2009 to December 2018 were collected. The digestive tract reconstruction methods included Billroth II anastomosis, Roux-en-Y anastomosis and un-cut-Roux- en-Y anastomosis. A linear stapler was used to transected the stomach and the duodenum. Among 1204 patients, 838 were males and 366 were females with mean age of (57.0±16.0) years. Duodenal stump was reinforced in 792 cases (reinforcement group) and unreinforced in 412 cases (non-reinforcement group). There were significant differences in resection range and anastomotic methods between the two groups (both P<0.001). The two groups were matched by propensity score according to the ratio of 1∶1, and the reinforcement group was further divided into purse string group and non-purse string group. The primary outcome was short-term postoperative complications (within one month after operation). Complications with Clavien-Dindo grade ≥ III a were defined as severe complications, and the morbidity of complication between the reinforcement group and the non-reinforcement group, as well as between the purse string group and the non-purse string group was compared. Results: After PSM, 411 pairs were included in the reinforcement group and the non-reinforcement group, and there were no significant differences in baseline data between the two groups (all P>0.05). No perioperative death occurred in any patient.The short-term morbidity of postoperative complication was 7.4% (61/822), including 14 cases of anastomotic leakage (23.0%), 11 cases of abdominal hemorrhage (18.0%), 8 cases of duodenal stump leakage (13.1%), 2 cases of incision dehiscence (3.3%), 6 cases of incision infection (9.8%) and 20 cases of abdominal infection (32.8%). Short-term postoperative complications were found in 25 patients (6.1%) and 36 patients (8.8%) in the reinforcement group and the non-reinforcement group, respectively, without significant difference (χ2=2.142, P=0.143). Nineteen patients (2.3%) developed short-term severe complications (Clavien-Dindo grade ≥IIIa), while no significant difference in severe complications was found between the two groups (1.7% vs. 2.9%, χ2=1.347, P=0.246). Sub-group analysis showed that the morbidity of short-term postoperative complication of the purse string group was 2.6% (9/345), which was lower than 24.2% (16/66) of the non-purse string group (χ2=45.388, P<0.001). Conclusion: Conventional reinforcement of duodenal stump does not significantly reduce the incidence of duodenal stump leakage, so it is necessary to choose whether to reinforce the duodenal stump individually, and purse string suture should be the first choice when decided to reinforce.

Liraglutide improves bone mineral density in osteoporotic rats by mediating O3a/Wnt signaling / 中华内分泌外科杂志

Objective:To study the effect of liraglutide on the forkhead box O3a (forkhead box O3a, FoxO3a) /Wnt signaling pathway and vertebral bone density in osteoporotic rats.Methods:Female Sprague-dawley rats were divided into sham operation group, model group, and liraglutide intervention group according to the random number table method, with 10 rats in each group. Both the model group and the intervention group used bilateral oophorectomy to establish an osteoporosis model. The intervention group was injected subcutaneously with liraglutide every day, and the sham operation group and the model group were given an equal volume of normal saline. After 12 weeks of continuous administration, the bone mineral density and bone biomechanics were measured, the serum osteoprotegerin, anti-tartrate acid phosphatase, and osteocalcin levels were detected by enzyme-linked immunosorbent assay, and the O3a/Wnt pathway was detected by Real-time PCR technology. The expression level of mRNA was detected by Western blot to detect the expression level of related proteins in the O3a/Wnt pathway.Results:The bone mineral density levels of L4,5 (0.33±0.04 vs 0.18±0.03) and left and right femurs (0.37±0.05 vs 0.23±0.04 0.35±0.04 vs 0.24±0.03) of the successfully modeled rats were significantly lower than those of the sham operation group ( P<0.05) . After 12 weeks of treatment, the differences in the maximum bone load, three-point bending stress, bone density and elastic modulus of the three groups of rats were statistically significant. Among them, the sham operation group had the highest level of each index (36.53±5.23, 154.13±6.27, 0.34±0.04, 3 102.34±160.44) , followed by the intervention group (19.37±4.32, 141.54±6.58, 0.18±0.03, 2 270.18±145.53) and the model group in turn (26.17±4.68, 147.56±5.84, 0.28±0.03, 2 804.24±140.42) ( P<0.05) . There were statistically significant differences in the levels of serum osteoprotegerin, anti-tartrate acid phosphatase and osteocalcin among the three groups. Among them, the osteoprotegerin (Sham operation group vs model group vs intervention group: 7.53±0.63 vs 4.57±0.42 vs 6.15±0.61) of the sham operation group was significantly higher than that of the intervention group and the model group. The anti-tartrate acid phosphatase (Sham operation group vs model group vs intervention group: 14.34±2.87 vs 19.53±3.52 vs 15.96±3.14) and osteocalcin levels (Sham operation group vs model group vs intervention group: 0.84±0.09 vs 1.13± 0.12 vs 0.95± 0.08) of rats The factor was significantly lower than that of the intervention group and model group ( P<0.05) . The mRNA and protein expression levels of FoxO3a, Wnt2, and β-catenin in the three groups of rats were significantly different. Among them, Wnt2 and β-catenin in the sham operation group were significantly higher than the intervention group and model group, and FoxO3a was significantly lower than the intervention group and model Group ( P<0.05) . Conclusion:Liraglutide can increase bone density and improve bone biomechanics by activating O3a/Wnt signal, thereby effectively treating osteoporosis.

Effect of Pien Tze Huang against EV71 / 中国中药杂志

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.

Analysis of genetic carrier of neonatal deafness in Hainan / 中国热带医学

@#Abstract: Objective　To explore the carrying status of four common deafness genes and mutations on 10 loci in newborns in Hainan, and to analyze the molecular epidemiological characteristics of deafness genes and their loci, so as to provide scientific basis for formulating neonatal deafness gene screening strategy and promoting children's hearing health in Hainan. Methods　Newborns born in Hainan from January 2020 to December 2021 were selected as the research objects. The demographic characteristics of the research objects were collected. At the same time, the plantar blood of newborns was collected, and multiplex PCR amplification and directed hybridization combined with high-throughput sequencing technology were applied to detect 10 mutation loci on 4 common deafness genes. T-test or chi square test was used to process the data. Results　A total of 7 124 newborns were included in the study through informed consent, 219 cases of deafness gene mutation were detected with the detection rate of deafness gene of 3.07%. The detection rates of GJB2, SLC26A4, MT-RNR1 and GJB3 were 1.56% (111/7 124), 1.18% (84/7 124), 0.21% (15/7 124) and 0.11% (8/7 124) respectively. Among the 10 loci of the four genes, the positive detection rate of c.235delC locus of GJB2 was the highest, which was 1.38% (98/7 124), followed by c.919-2A>G of SLC26A4 (0.87%, 62/7 124); 2.63% (113/4 289) of the newborns who passed the preliminary hearing screening still carried the deafness gene; in terms of gene type, the detection rate of GJB2 gene in newborns who failed the hearing screening was higher than that in newborns who passed the hearing screening [2.23% (63/7 124) vs 1.12% (48/7 124)，P<0.01]; in terms of gene loci, the detection rate of c.235delC locus in newborns who failed hearing screening was higher than that in newborns who passed hearing screening [2.09% (59/7 124) vs 0.91% (39/7 124)，P<0.01]. Conclusion　The most common deafness genes types in Hainan were GJB2 and SLC26A4; The most common gene mutation sites were c.235delC and c.919-2A>G; 2.63% of the newborns who passed the preliminary hearing screening still carried the deafness gene, among which the high-risk newborns with MT-RNR1 and GJB3 genes were found. Therefore, hearing screening should be combined with deafness gene screening to improve the detection rate of children at high risk of hearing loss.

Comparison of clinical efficacy and quality of life between uncut Roux-en-Y and Billroth II with Braun anastomosis in laparoscopic distal gastrectomy for gastric cancer / 中华胃肠外科杂志

Objective: To compare the clinical efficacy and quality of life between uncut Roux-en-Y and Billroth II with Braun anastomosis in laparoscopic distal gastrectomy for gastric cancer patients. Methods: A retrospective cohort study was performed. Inclusion criteria: (1) 18 to 75 years old; (2) gastric cancer proved by preoperative gastroscopy, CT and pathological results and tumor was suitable for D2 radical distal gastrectomy; (3) postoperative pathological diagnosis stage was T1-4aN0-3M0 (according to the AJCC-7th TNM tumor stage), and the margin was negative; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, and American Association of Anesthesiologists (ASA) grade 1 to 3; (5) no mental illness; (6) able to answer questionnaires independently; (7) patients agreed to undergo laparoscopic distal gastrectomy and signed an informed consent. Exclusion criteria: (1) patients with severe chronic diseases and American Association of Anesthesiologists (ASA) grade >3; (2) patients with other malignant tumors; (3) patients suffered from serious mental diseases; (4) patients received neoadjuvant chemotherapy or immunotherapy. According to the above criteria, clinical data of 200 patients who underwent laparoscopic distal gastrectomy at the Department of General Surgery of the First Affiliated Hospital of Army Medical University from January 2016 to December 2019 were collected. Of the 200 patients, 108 underwent uncut Roux-en-Y anastomosis and 92 underwent Billroth II with Braun anastomosis. The general data, intraoperative and postoperative conditions, complications, and endoscopic evaluation 1 year after the surgery were compared. Besides, the quality of life of two groups was also compared using the Chinese version of the European Organization For Research and Treatment of Cancer (EORTC) quality of life questionnaire-Core 30 (QLQ-C30) and quality of life questionnaire-stomach 22 (QLQ-STO22). Results: There were no significant differences in baseline data between the two groups (all P>0.05). All the 200 patients successfully underwent laparoscopic distal gastrectomy without intraoperative complications, conversion to open surgery or perioperative death. There were no significant differences between two groups in operative time, intraoperative blood loss, postoperative complications, time to flatus, time to removal of gastric tube, time to liquid diet, time to removal of drainage tube or length of postoperative hospital stay (all P>0.05). Endoscopic evaluation was conducted 1 year after surgery. Compared to Billroth II with Braun group, the uncut Roux-en-Y group had a significantly lower incidences of gastric stasis [19.8% (17/86) vs. 37.0% (27/73), χ(2)=11.199, P=0.024], gastritis [11.6% (10/86) vs. 34.2% (25/73), χ(2)=20.892, P<0.001] and bile reflux [1.2% (1/86) vs. 28.8% (21/73), χ(2)=25.237, P<0.001], and the differences were statistically significant. The EORTC questionnaire was performed 1 year after surgery, there were no significant differences in the scores of QLQ-C30 scale between the two groups (all P>0.05), while the scores of QLQ-STO22 showed that, compared to the Billroth II with Braun group, the uncut Roux-en-Y group had a lower pain score (median: 8.3 vs. 16.7, Z=-2.342, P=0.019) and reflux score (median: 0 vs 5.6, Z=-2.284, P=0.022), and the differences were statistically significant (all P<0.05), indicating milder symptoms. Conclusion: The uncut Roux-en-Y anastomosis is safe and reliable in laparoscopic distal gastrectomy, which can reduce the incidences of gastric stasis, gastritis and bile reflux, and improve the quality of life of patients after surgery.

The Gender-Sensitive Social Risk Factors for Internet Addiction in College Undergraduate Students

Objective@#The current study aims to explore precipitating and social risk factors for internet addiction (IA) in university undergraduate students, and to provide evidence for interventions and the early prevention of IA in different genders. @*Methods@#Four thousand eight hundred and fifty-eight college sophomores completed an online survey on their internet use-related behaviours and social risk factors. @*Results@#We found that more male (8.3%) than female students (5.4%) had moderate and severe IA. The main online activity in the moderate and severe IA groups was online gaming in males and online streaming in females. Roommates engaging in similar internetbased entertainment was a risk factor of IA only for males, while not being in a romantic relationship was a risk factor of IA for females only. Infatuation with the internet before college and adjustment problems for college life were shared risk factors for both genders in the mild and moderate IA groups. @*Conclusion@#IA was a common phenomenon in college students with shared and unique precipitating and social risk factors in males and females. The gender-sensitive risk factors for IA warranted earlier and individualized intervention and prevention strategies for IA in this population.

The Gender-Sensitive Social Risk Factors for Internet Addiction in College Undergraduate Students

Objective@#The current study aims to explore precipitating and social risk factors for internet addiction (IA) in university undergraduate students, and to provide evidence for interventions and the early prevention of IA in different genders. @*Methods@#Four thousand eight hundred and fifty-eight college sophomores completed an online survey on their internet use-related behaviours and social risk factors. @*Results@#We found that more male (8.3%) than female students (5.4%) had moderate and severe IA. The main online activity in the moderate and severe IA groups was online gaming in males and online streaming in females. Roommates engaging in similar internetbased entertainment was a risk factor of IA only for males, while not being in a romantic relationship was a risk factor of IA for females only. Infatuation with the internet before college and adjustment problems for college life were shared risk factors for both genders in the mild and moderate IA groups. @*Conclusion@#IA was a common phenomenon in college students with shared and unique precipitating and social risk factors in males and females. The gender-sensitive risk factors for IA warranted earlier and individualized intervention and prevention strategies for IA in this population.

Herbal textual research on Chuanxiong Rhizoma in Chinese classical prescriptions / 中国中药杂志

Fourteen classical prescriptions in the Catalog of 100 Ancient Classical Prescriptions(First Batch) promulgated in 2018 contain Chuanxiong Rhizoma, which reveals the high medicinal value and wide application of Chuanxiong Rhizoma. This paper systematically reviews the ancient herbal books and modern literature to explore the name, origin, genuine producing area, medicinal part, harvesting, and processing of Chuanxiong Rhizoma, thus facilitating the development of classical prescriptions containing Chuan-xiong Rhizoma. It is confirmed that Chuanxiong Rhizoma, formerly known as "Xiongqiong" in Chinese, was first called "Chuanxiong" in late Tang Dynasty, which has been gradually accepted as its official name due to the rise of the status of Chuanxiong Rhizoma produced in Sichuan. The main original plant of Chuanxiong Rhizoma in past dynasties has always been deemed to be Ligusticum chuan-xiong(Umbellifera), whose rhizome serves as the medicinal part. In general, it is best harvested in summer but the harvesting time can vary with different growth environments. Since the Song Dynasty, Sichuan province has been recognized as the genuine producing area of Chuanxiong Rhizoma in light of the high yield and good quality. It is suggested that Chuanxiong Rhizoma from Sichuan be used preferentially in the development of classical prescriptions. There are multiple processing methods of Chuanxiong Rhizoma recorded in ancient medical classics, and the raw(after purifying and slicing) or wine-processed or stir-fried Chuanxiong Rhizoma is still in use today. In the development of classical prescriptions containing Chuanxiong Rhizoma, Chuanxiong Rhizoma is advised to be processed in accordance with current processing standards if the specific processing method is described in the medical classics. If not, the raw Chuanxiong Rhizoma is preferred and then processed following the processing standards of Chuanxiong Rhizoma decoction pieces in Chinese Pharmacopoeia.

Application IPSA combined with increasing cervical center dose in intracavitary and interstitial brachytherapy for locally advanced cervical cancer / 中华放射肿瘤学杂志

Objective:To analyze the advantages of IPSA combined with increasing cervical center dose in intracavitary and interstitial brachytherapy (IC/IS) for locally advanced cervical cancer.Methods:A total of 46 stage Ⅱ B cervical cancer patients with, local lesion size≥5 cm after 45 Gy/25f external intensity-modulated radiotherapy (IMRT) were recruited. Uterine tandem and needles were implanted, CT was performed, and then HR-CTV, rectum, bladder, sigmoid colon and the area of cervix increased dose (HR-cervix) were delineated, IPSA was used for optimization. According to whether the dose of HR-cervix was increased or not, all patients were divided into IC/IS+ HR-cervix group (group A) and IC/IS group (group B). The differences in dosimetric parameters were compared between two groups. Results:The relative uterine tandem dwell time was significantly extended in group A ( P<0.001). In group B, the V 150% and V 200% volumes of HR-cervix were increased from 63.94% and 30.80% to 91.54% and 64.06%. The D 90% and D 100% in group A were significantly lower than those in group B (both P<0.05). There was no statistical difference in organ at risk (OAR) dose. Conclusion:IPSA combined with increasing cervical center dose can meet the HR-CTV D 90% dose requirement, normal tissue dose limits, and can escalate the doses to local areas of the cervix.

Physical and neuropsychological development of children with Citrin deficiency / 中国当代儿科杂志

OBJECTIVES@#To study the physical and neuropsychological development of children with Citrin deficiency (CD).@*METHODS@#A total of 93 children, aged 1.9-59.8 months, who were diagnosed with CD by @*RESULTS@#For the 93 children with CD, the incidence rate of failure to thrive was 25% (23 children) and the proportion of small for gestational age was 47% (44 children). For the 100 cases of CD, the incidence rates of growth retardation, underweight, emaciation, overweight, and microcephalus were 23% (23 cases), 14% (14 cases), 4% (4 cases), 8% (8 cases), and 9% (9 cases), respectively. The incidence rate of neuropsychological developmental delay was 25% (25 cases), and the incidence rates of development delay in the five domains of adaptability, gross motor, fine motor, language, and social ability were 7% (7 cases), 15% (15 cases), 7% (7 cases), 9% (9 cases), and 7% (7 cases), respectively.@*CONCLUSIONS@#Physical and neuropsychological developmental delay can be observed in children with CD, and physical and neuropsychological development should be regularly assessed.

Altered Splicing in Stable Cell Strains Expressing Mini-hF9 Gene with Nonsense Mutation / 中国实验血液学杂志

OBJECTIVE@#To investigate the molecular mechanism in stable cell strains expressing Mini-hF9 gene with nonsense mutation.@*METHODS@#Mini-hF9 gene and its nonsense mutants were transfected into HeLa cells independently, and stable cell strains were obtained after G418 resistance screening and monoclonal transformation. The altered splicing and protein expression of mRNA in Mini-hF9 gene in stable cell strains were detected by using RT-PCR and Western blot.@*RESULTS@#The wild type and nonsense mutated human coagulation factor IX stable cell strains were constructed successfully, which were named HeLa-F9-WT, HeLa-F9-M1 and HeLa-F9-M2. Only normal splicing Norm was detected in the wild-type cell strain HeLa-F9-WT; Norm and Alt-S1 splicing were detected in HeLa-F9-M1; while Norm, Alt-S1 and Alt-S2 splicing were detected in HeLa-F9-M2.@*CONCLUSION@#The nonsense associated altered splicing (NAS) pathway, which generated alternately spliced transcripts, might be triggered in coagulation factor IX gene with nonsense mutation.

miR-4417 suppresses keloid fibrosis growth by inhibiting CyclinD1

Mounting evidence has reported that microRNAs (miRNAs) play irreplaceable roles in the development ofkeloid fibrosis. miR-4417 has been reported to contribute to nickel chloride-promoted lung epithelial cellfibrogenesis and tumorigenesis. However, whether miR-4417 is involved in keloid fibrogenesis as well as itsunderlying mechanisms remain largely elusive. In this study, the expression levels of miR-4417 and CyclinD1in keloid tissues and fibroblasts were examined by qRT-PCR. Cell proliferation was determined by CCK assay.Western blot and flow cytometry were performed to evaluate cell apoptosis. Cell migration and invasion weremeasured by Transwell assay. Luciferase reporter assay was used to confirm the relationship between miR4417 and CyclinD1. As a result, we found that miR-4417 was significantly down-regulated in keloid tissuesand fibroblasts. miR-4417 up-regulation led to the suppression of proliferation, migration, and invasion, whileinduced cell apoptosis in keloid fibroblasts. However, miR-4417 depletion exerted an opposite effect.CyclinD1 harbored the binding sites with miR-4417. Besides, the expression of CyclinD1 was evidentlydecreased in keloid tissues and fibroblasts. Meanwhile, miR-4417 was negatively correlated with CyclinD1 inkeloid tissue. The effect of CyclinD1 knockdown on keloid fibroblasts was similar to that of miR-4417overexpression. Furthermore, the elevated of CyclinD1 expression rescued the effect of miR-4417 up-regulation on keloid fibroblasts. miR-4417/CyclinD1 axis was required for cell proliferation, apoptosis, migration,and invasion in keloid fibroblasts. In conclusion, miR-4417 and CyclinD1 may be potential therapeutic targetsfor the treatment of keloid.

Serological feature and molecular mechanism for a case with A307 subgroup / 中华医学遗传学杂志

OBJECTIVE@#To explore the serological feature and molecular mechanism for a case with A307 subgroup of the ABO blood group system.@*METHODS@#Serological assay was carried out to determine the ABO blood group of the proband and his family members. Genotypes for exons 1 to 7 of the ABO gene were determined with sequence-specific primer polymerase chain reaction (SSP-PCR) and direct sequencing. The impact of the variant on the stability of alpha-1,3-N-acetylgalactosaminyltransferase (GTA) was predicted through construction of a 3D molecular model.@*RESULTS@#The proband, his brother and daughter were diagnosed with Aend phenotype by serological analysis. Their ABO genotype was determined as A307/O02, with heterozygous c.467C>T (p.P156L) and c.745C>T (p.R249W) variants identified in exon 7 of the ABO gene. Molecular modeling suggested that the p.R249W variant may alter the number of hydrogen bonds between the amino acids. The protein was predicted to have a decreased Δ Δ G value of thermodynamic stability.@*CONCLUSION@#The p.R249W variant may give rise to the A307 subgroup by reducing the stability of the GTA enzyme, leading to serological features of Aend phenotype.

LC-MS/MS analysis of pazufloxacin in human plasma and otorrhea: application to a pharmacokinetic study of ear drops / 药学学报

Pazufloxacin eardrops are a topical quinolone agent for the treatment of outer ear infection. The present study evaluated the pharmacokinetics and topical distribution of pazufloxacin eardrops by a sensitive LC-MS/MS method for determining pazufloxacin in plasma and otorrhea. Plasma and otorrhea samples were extracted by acetonitrile-induced protein precipitation and were subjected to liquid chromatography-tandem mass spectrometric analysis with an electrospray ionization interface. The samples were separated on an HSS T3 column (50 mm×2.1 mm, 1.8 μm). To avoid the matrix effect, gradient elution was performed with the mobile phase consisting of methanol and 1 mmol·L-1 ammonium acetate aqueous solution (0.1% formic acid). The ion transitions for pazufloxacin and pazufloxacin-d4 were m/z 319.1→281.2 and m/z 323.1→285.2, respectively, under the multiple reaction monitoring (MRM) mode. The method was linear in the range of 0.010 0 - 8.00 ng·mL-1 for pazufloxacin in plasma and 0.500 - 1 000 ng·mg-1 in otorrhea. The intra- and inter-day accuracy and precision for pazufloxacin in plasma and in otorrhea met acceptable criteria. The clinical trial was approved by the Society of Ethics and conducted in Nanjing First Hospital and Jiangsu Province Hospital. The validated methods were used in a systemic and topical pharmacokinetic study of 0.1% pazufloxacin eardrops in 3 patients with chronic suppurative otitis media.

The mechanism of action of Fuzi-Lizhong pill in treatment of ulcerative colitis based on network pharmacology-molecular docking / 药学学报

Network pharmacology and bioinformatics technology were used to predict the mechanism of action of Fuzi-Lizhong pill (FLP) in the treatment of ulcerative colitis (UC). 26 components (23 prototype compounds and 3 metabolites) in the blood of FLP were selected as the research objects. PharmMapper database, SwissTargetPrediction platform, GeneCards and OMIM database were used to screen and predict potential targets of FLP in blood. The protein-protein interaction network model was constructed by using String database and Cytoscape software. DAVID platform, KEGG and Reactome databases were used for GO analysis and pathway analysis of potential targets. Network of drug ingredients-targets-pathways was constructed by Cytoscape software. AutoDock vina software was used to dock the molecules of the absorbed ingredients of FLP in blood with the key targets. 82 potential targets of FLP for treatment of UC were obtained. Potential targets mainly involve biological processes such as response to organic substance, regulation of apoptosis, regulation of programmed cell death, which played roles in the treatment of UC by adjusting pathways in cancer, Colorectal cancer, Vascular endothelial growth factor signaling pathway, Mitogen-activated protein kinase signaling pathway, arachidonic acid metabolism and the other signal pathways. From the perspective of network pharmacology, this study predicted the mechanisms of action of FLP in treating UC, indicating that FLP in treating UC had the characteristics of multiple ingredients, multiple targets and multiple pathways, which laid a foundation for further research.

Effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4 in patients with allergic rhinitis in Hainan area / 临床耳鼻咽喉头颈外科杂志

The aim of this study is to investigate the effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4（sIgG4） in patients with allergic rhinitis （AR） in Hainan area. Seventy-two patients with dust-mite allergic rhinitis, all three generations of whom were local islanders in Hainan, were randomly divided into control group（36 cases） and SLIT group（36 cases）. sIgG4 and sIgE expression levels were detected before treatment, 6 months after treatment, 12 months after treatment, and 18 months after treatment. The patient's symptom score, medication score, VAS score and adverse reactions was also assessed. Finally, through statistical analysis of the relevant data collected at 4 time points in the two groups of patients, the efficacy, safety and changes of sIgG4 antibody expression level in patients with allergic rhinitis receiving sublingual specific immunotherapy in Hainan were observed. Symptoms scores, medication scores and VAS scores were significantly improved in the SLIT group after treatment compared with before treatment（0.05）. In the control group, symptom scores, medication scores and VAS scores were also significantly improved compared with before treatment（0.05）. When comparing the two groups, Symptoms scores, medication scores and VAS scores of the SLIT group were significantly lower than those of the control group at 12 months and 18 months after treatment（0.05）. No severe systemic adverse reactions occurred in the two groups, and 3 patients showed mild adverse reactions in the SLIT group. Sublingual immunotherapy of Dermatophagoides Farinae was effective and could increase the expression of sIgG4 in patients with Dermatophagoides farinae AR, sIgG4 is expected to be an immunological marker for the objective evaluation of the clinical efficacy of Hapten.

Prescription Law of New Coronavirus Pneumonia in Different Stages / 中国实验方剂学杂志

Objective:To study the clinical medication regulation for the prevention and treatment of new coronavirus pneumonia with traditional Chinese medicine（TCM），especially prescriptions，on the basis of "treatment in accordance with seasonal conditions". Method:The guidelines and suggestions on novel coronavirus pneumonia formulated and published by national，provincial and municipal governments and experts before February 17，2020, were retrieved and summarized. Data was recorded in stages according to "prevention period，clinical observation period，pre-clinical period，middle clinical period，late clinical period and recovery period". The frequency analysis of TCM and its efficacy，prescription and proprietary Chinese medicine was carried out，and then the factor analysis and cluster analysis of TCM were carried out to obtain rational drug combinations. Result:Totally 172 suggestions on combined structure of drugs，50 suggestions on prescriptions and 31 suggestions on proprietary Chinese medicine were involved in the study，and provided by 24 official agencies and 24 medical experts， 147 kinds of herbs，44 prescriptions and 16 proprietary Chinese medicines were collected. No matter for the drug category or for the specific drug selection，the law of drug use in different stages was not the same. Huoxiang Zhengqi capsule，Shufeng Jiedu capsule，Lianhua Qingwen capsule and Jinhua Qinggan capsule can be used in the observation period. Xuanbai Chengqitang can be used in the middle of the disease. Angong Niuhuangwan，Suhexiangwan or Zixuedan, and Angong Niuhuangwan can be selected in the middle of the disease. And Qingfei Paidu decoction can be used in all stages of the disease. Conclusion:Doctors need to adjust their prescriptions along with the progress of the disease，because the law of medication in each stage of the new coronavirus pneumonia is different.

Study on the economic evaluation of hospital-based health technology assessment / 中华医院管理杂志

Different from the traditional health technology assessment(HTA), hospital-based health technology assessment(HB-HTA) is mainly based on the perspective of the hospital to carry out economic analysis, commonly used cost-effectiveness analysis combined with budget impact analysis methods. It pays attention to the current medical costs and effects, and supports the hospital′s internal health technology access, purchase pricing, elimination and other decisions. In the context of deepening the reform of medical insurance payment mode in China, the hospital internal medicine decision-making based on HB-HTA is particularly important. Based on the economic characteristics of health technology, the authors analyzed the differences between HB-HTA and traditional HTA in carrying out economic evaluation, introduced the steps, contents, indicators and methods of HB-HTA economic evaluation, and put forward relevant strategic suggestions.