Advances of pathogenesis and drug development in amyotrophic lateral sclerosis / 中国药理学通报

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

The Experience of Nurses’ Moral Dilemma in Intensive Care Unit: A Qualitative Study / 中国医学伦理学

【Objective:】 To understand the true experience and feelings of nurses in the intensive care unit on the clinical experience of moral dilemmas, and to provide strategies for reducing the impact of moral dilemmas. 【Methods:】 Thirteen nurses in the intensive care unit were interviewed face to face by descriptive nature research method. The traditional content analysis method were used to compute the data, and the coding, categorization and topic extraction were carried out cyclically until the data were saturated and the interview was stopped. 【Results:】 The moral dilemma experience of nurses in the intensive care unit had the following three themes: negative psychological experience, negative behavior experience, and life and death cognitive experience. 【Conclusion:】 Nurses in the intensive care unit will have complex negative experiences after experiencing moral dilemmas. This negative experience threatens nurses’ mental health. Nursing managers should pay attention to the impact of moral dilemmas on nurses and formulate effective measures, thereby ensure nursing safety and maintain the healthy development of the nursing team.

Follicular lymphoma with a predominantly diffuse growth pattern with 1p36 deletion: a clinicopathologic analysis of eight cases / 中华病理学杂志

Objective: To investigate the clinical and pathologic features and diagnosis of follicular lymphoma (FL) with a predominantly diffuse growth pattern (DFL) with 1p36 deletion. Methods: Eight cases of DFL with 1p36 deletion diagnosed at Department of Pathology, Beijing Friendship Hospital, Capital Medical University (n=5) and the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital (n=3) from January 2017 to January 2023 were included. Their clinicopathologic features and follow-up data were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed. Results: There were five males and three females, with a median age of 67 years, and inguinal lymphadenopathy was found as the main symptom. Histologically, similar morphologic features were sheared among all cases, with effaced nodal structure and characterized by proliferation of centrocytes in a diffuse pattern, with or without follicular components. The germinal center-related markers such as CD10 and/or bcl-6 were expressed in the tumor cells, and 1p36 deletion but not bcl-2 translocation was appreciable in these cases. Conclusions: DFL with 1p36 deletion is a rare subtype of FL, with some overlaps with other types of FL or indolent B-cell lymphomas in their pathologic features. An accurate diagnosis requires comprehensive considerations based on their clinical, pathologic, immunohistochemical, and molecular features.

Effect mechanism research of procyanidin on gingivitis rats by regulating the PI3K/Akt/VEGF signal pathway / 中国药房

OBJECTIVE To investigate the potential mechanism of procyanidin on rats with gingivitis by regulating phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/vascular endothelial growth factor （VEGF） signaling pathway. METHODS The rat model of gingivitis was constructed by sewing the neck of the first maxillary molar with silk thread+applying maltose on the gum+feeding with 20% sucrose solution and soft food. Forth-eight model rats were randomly divided into model group， procyanidin group （160 mg/kg）， 740Y-P group （PI3K/Akt signaling pathway activator， 0.02 mg/kg）， and procyanidin+ 740Y-P group （procyanidin 160 mg/kg+740Y-P 0.02 mg/kg）， with 12 rats in each group； another 12 rats were selected as control group； each medication group was treated with corresponding drugs intragastrically or/and intraperitoneally， once a day， for 7 consecutive days. Twenty-four hours after the last administration， the gingival index of rats was measured； the levels of interleukin- 18 （IL-18）， inducible nitric oxide synthase （iNOS） and alkaline phosphatase （ALP） in gingival crevicular fluid， as well as the levels of superoxide dismutase （SOD）， catalase （CAT） and reactive oxygen species （ROS） in gingival tissues of rats were detected； the pathological changes in gingival tissues were observed； the expression levels of PI3K/Akt/VEGF signaling pathway- related proteins in gingival tissues of rats were detected. RESULTS Compared with control group， the gingival tissues of rats in the model group had severe pathological damage，which was manifested as local tissue expansion and congestion， new capillaries， degeneration and loss of collagen fibers and disorder of arrangement， and a large number of inflammatory cell infiltration in the gingival sulcus wall. The gingival index， the levels of IL-18， iNOS， ALP in gingival crevicular fluid， the level of ROS in gingival tissues， the phosphorylations of PI3K and Akt， as well as the protein expression of VEGF in gingival tissues were significantly increased； the levels of SOD and CAT in gingival tissues of rats in model group were significantly decreased （P＜0.05）. Compared with model group， the pathological damage to the gingival tissues of rats in procyanidin group was reduced， and all quantitative indicators were significantly improved （P＜0.05）； 740Y-P could reverse the improvement effect of procyanidin on various indicators （P＜0.05）. CONCLUSIONS Procyanidin may alleviate gingival tissue damage， and improve gingival inflammation and oxidative stress in rats with gingivitis by inhibiting PI3K/Akt/VEGF signaling pathway.

Analysis of a child with neurodevelopmental disorders due to variant of HNRNPU gene and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic variant in a child with neurodevelopmental disorders (NDDs).@*METHODS@#Clinical data of a child who had presented at Xiaogan Hospital Affiliated to Wuhan University of Science and Technology in December 2020 due to intermittent convulsions for over a year were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. "HNRNPU gene", "epilepsy", "epileptic encephalopathy", "hereditary epilepsy", "neurodevelopmental disorder", "neurodevelopmental syndrome", "HNRNPU", and "NDDs" were used as the key words to search the CNKI, Wanfang and PubMed databases dated from January 1, 1994 to February 10, 2022.@*RESULTS@#The patient was a 2-year-old boy who had developed seizure at the age of 5 months. His clinical features had included abnormal appearance, recurrent seizures, and low developmental quotients of each functional area as evaluated by the Gesell scale. The child was given sodium valproate for the antiepileptic treatment and rehabilitation training. He had become seizure-free within half a year of follow-up, but his intelligence and motor development did not improve significantly. Genetic testing revealed that he has harbored a heterozygous c.1720_1722delCTT (p.Lys574del) variant of the HNRNPU gene, which was not found in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS2+PM2_Supporting+PM4). A total of 13 articles were retrieved, and the types of HNRNPU gene mutations have included splice site mutation, nonsense mutation, missense mutation, in-frame deletion, gene duplication, frameshifting mutation, and multiple exon deletion. The main clinical manifestations have included mental retardation, language delay, global developmental delay, epilepsy, craniofacial deformity, mental and behavioral abnormalities.@*CONCLUSION@#The c.1720_1722delCTT variant of the HNRNPU gene probably underlay the NDDs in this child. Above finding has enriched the mutational spectrum of the HNRNPU gene.

A multicenter study assessing the efficacy of various preoperative/pre-transfusion screening methods for blood transmitted disease / 中华检验医学杂志

Objective:This multi-centre study was conducted to assess the efficacy of various preoperative/pre-transfusion screening methods for blood transmitted disease.Methods:From July 2021 to December 2021, plasma samples of patients admitted to 10 hospitals were collected for screening preoperative/pre-transfusion blood transmitted disease. Nucleic acid detection technology was used to detect hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA and human immunodeficiency virus (HIV)(1+2) RNA, and the results were compared with the immuno-serological methods. χ 2 test and Kappa test were used to analyze the efficacy of these two methods. Results:A total of 8 655 valid specimens were collected from 10 hospitals. There was a statistically significant difference in the positive detection rate of HCV between the two methods ( P<0.001). There was no significant difference in the positive detection rate of HBV and HIV assessed by the two methods ( P>0.05), but the number of positive cases detected by HBV DNA and HIV RNA (218 and 4 cases) was significantly higher than the corresponding serological results (216 and 2 cases). At the same time, there were HBV, HCV and HIV immuno-serological omissions by the immuno-serological methods, among which 28 cases were HBsAg negative and HBV DNA positive, 2 cases were HCV antibody negative and HCV RNA positive, and 2 cases were HIV antigen/antibody negative and HIV RNA positive. In addition, in the 66 samples with inconsistent results from the two detection methods, 83.3% (55/66), 68.2% (45/66), 63.6% (42/66) and 62.1% (41/66) of patients aged was>45 years, tumor, surgery and male, respectively. Conclusions:Compared with immuno-serological tests, nucleic acid tests have the advantage in terms of sensitivity on detecting HBV, HCV and HIV infection and could reduce missed detection. The risk of transmission can be reduced by adding HBV, HCV, and HIV nucleic acid tests to preoperative/pre-transfusion immuno-serological tests screening for patients over 45 years of age and tumor patients.

Clinical value of nucleic acid detection for hepatitis B virus screening in hospitalized patients / 中华检验医学杂志

Objective:To explore clinical value of nucleic acid detection for hepatitis B virus (HBV) screening in hospitalized patients.Methods:This cross-sectional study collected and analyzed plasma samples from patients admitted to 10 domestic medical institutions from July 2021 to December 2021. Serological immunoassay and nucleic acid screening were used to simultaneously detect hepatitis B markers such as hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e Antigen (HBeAg), hepatitis B e antibody (HBeAb), hepatitis B core antibody (HBcAb),and HBV DNA. Statistical analysis was performed on the serology, nucleic acid test results and clinical information of the patients.Results:Of the 8 655 collected samples, HBsAg was positive in 216 (2.50%) samples,HBV DNA was positive in 238 (2.75%) samples ( P>0.05); 210 (2.43%) samples were positive for both HBsAg and HBV DNA, 28 (0.32%) were HBsAg negative and HBV DNA positive, 6 cases (0.07%) were HBsAg positive and HBV DNA negative. Conclusion:These results indicate that the HBV DNA testing is equally effective as hepatitis B virus serological detection for hepatitis B virus screening in hospitalized patients.

Clinical significance of hepatitis B virus DNA detection in screening patients with hepatitis B / 中华检验医学杂志

Objective:To explore the clinical significance of hepatitis B virus (HBV) DNA detection in screening patients with hepatitis B.Methods:Clinical data of 682 331 hepatitis B patients were retrospectively analyzed. The HBV DNA of these patients was detected in the Fifth Medical Center of the PLA General Hospital from January 2017 to December 2021, there were 481 159 males and 201 172 females in this cohort, the average age was (41.34±16.13) years. Patients were divided into HBV DNA positive group (219 879 cases) and HBV DNA negative group (462 452 cases). Clinical characteristics, data of five serologic markers of hepatitis B and hepatitis B surface antigen quantification (HBsAg-QN), liver function, alpha fetoprotein (AFP) and prothrombin time (PT) results were collected and analyzed and compared between the two groups.Results:The positive rate of HBV DNA was 32.22% (219 879/682 331) in this cohort. Among the different age groups, the positive rate of HBV DNA was the highest (40.34%, 128 038/317 380) in young people aged 18-44 years. The proportion of patients was lower among aged <1, 45-59 and ≥60 years patients in HBV DNA positive group than that in HBV DNA negative group, while the proportion of patients was higher among aged 1-17 and 18-44 years patients in HBV DNA positive group than that in HBV DNA negative group (all P<0.001). Among 2 291 <1-year-old infants tested for HBV DNA, 71 infants were HBV DNA positive. The positive rates of HBV DNA from 2017 to 2021 were 4.86% (27/556), 3.68% (14/380), 3.47% (17/490), 1.55% (6/386) and 1.46% (7/479) respectively, showing a downward trend year by year. The positive rate of HBV DNA in acute hepatitis B (AHB) patients was the highest (49.88%, 208/417) among 680 040 patients with hepatitis B. The proportion of AHB patients (0.09%, 208/219 808) and chronic hepatitis B (80.44%, 176 806/219 808) in HBV DNA positive group was higher than that in HBV DNA negative group [0.05% (209/460 232) and 65.45% (301, 216/460 232)], while the proportion of patients with HBV-related liver cirrhosis (11.28%, 24 793/219 808), HBV-related liver cancer (6.72%, 14 775/219 808), liver cancer surgery (1.39%, 3 055/219 808) and liver transplantation (0.08%, 171/219 808) were lower than that in HBV DNA negative group [22.99% (105 813/460 232), 7.25% (33 385/460 232), 3.50% (16 129/460 232) and 0.76% (3 480/460 232)] (all P<0.001). At the same time, positive rate of hepatitis B surface antigen (HbsAg), HBsAg-QN, hepatitis B e antigen (HbeAg), level of total bilirubin, total bilirubin, AFP and PT were higher in HBV DNA positive group than those in HBV DNA negative group, while the age, male ratio and albumin results in HBV DNA positive group were lower than those in HBV DNA negative group (all P<0.01). The HBV DNA loads were higher in HBsAg positive group, hepatitis B surface antibody positive group and HBeAg positive group than those in respective negative groups, while the HBV DNA loads were lower in hepatitis B e antibody positive group and hepatitis B core antibody positive group than those in respective negative groups (all P<0.001). Conclusions:The mother to child transmission rate of<1-year-old infants decreases year by year. HBV DNA is an important factor for the progression of hepatitis B disease. HBV DNA positive hepatitis B patients with higher HBsAg-QN values are more likely to have abnormal serum markers such as liver dysfunction. HBV DNA detection is therefore of clinical importance in screening patients with hepatitis B.

A case report of bilateral chylous hemothorax presenting after laparoscopic renal pedicle lymphatic disconnection / 中华泌尿外科杂志

Laparoscopic renal pedicle lymphatic disconnection is the most effective method for treating chyluria that has failed to respond to conservative management. Chylous hemothorax is a rare clinical occurrence resulting from the anatomic abnormality. This paper reported a case, who was admitted with painless gross hematuria for 1 month and was diagnosed with left chylous hematuria. Laparoscopic left renal pedicle lymphatic disconnection was performed, and bilateral chylous hemothorax occurred after the operation. After conservative treatment such as bilateral closed thoracic drainage and blood transfusion support, the patient recovered well. After 2 months of follow-up, there was no obvious effusion in the bilateral thoracic cavity, and the chylous test of urine fluid was negative.

Interaction between hyperuricemia and gender on dyslipidemia in the elderly / 中华健康管理学杂志

Objective:To explore the interaction between hyperuricemia and gender on dyslipidemia in the elderly.Methods:A cross-sectional study. The permanent residents aged≥65 years in Kunshan City were selected by the cluster sampling method. The selected residents underwent physical examination and blood biochemical tests such as blood glucose, blood lipid, uric acid, hyaluronic acid, gamma glutamyltransferase and creatinine, and history of schistosomiasis infection was investigated. Multivariate logistic regression analysis was used to analyze the relationship between various factors and dyslipidemia. Synergy index (S), relative excess risk of interaction (RERI) and the attributable proportion due to interaction (AP) were used to evaluate the association between hyperuricemia and female interaction on dyslipidemia.. The dose-response relationship between serum uric acid level and dyslipidemia was analyzed by a restricted cubic spline regression model.Results:The prevalence of dyslipidemia in the elderly aged 65 years and obove was 31.9% (1 450/4 536), and it was 23.7% (517/2 180) and 39.6% (933/2 356) in men and women, respectively ( χ2=131.38, P<0.001). Multivariate regression showed that female, high waist circumference, overweight and obesity, hypertension, diabetes, low glomerular filtration rate, high gamma-glutamyltranspeptidase, high uric acid to creatinine ratio, low neutral to lymphocyte ratio were associated with dyslipidemia (all P<0.05). Additionally, additive interaction association was found between the dyslipidemia and advanced uric acid levels ( OR=1.09, 95% CI: 1.07-1.12) and female ( OR=1.12, 95% CI: 1.11-1.14), and the contribution rate of interaction effects was 19.8% (RERI=0.74, 95% CI: 0.06-1.42; AP=0.20, 95% CI: 0.04-0.36, S=1.37, 95% CI: 1.02-1.84). Non-linear dose response relationship was identified by the restricted cubic spline regression model between the continuously rising serum uric acid and dyslipidemia ( χ2=101.23, P<0.001). Conclusions:The proportion of dyslipidemia in elderly permanent residents is high. Demographics and physical measurement indicators comprehensively affected the prevalence of dyslipidemia. In addition, both hyperuric acid and female have additive interaction on dyslipidemia.

Application value of ERCP in the diagnosis and treatment of pancreaticobiliary maljunction in children / 中华胰腺病杂志

Objective:To investigate the application value of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment of pancreaticobiliary maljunction (PBM) in children.Methods:The clinical data of 77 PBM children who underwent ERCP in General Surgery Department of Children's Hospital affiliated to Nanjing Medical University between January 2018 and December 2021 were retrospectively evaluated. Clinical characteristics, classification and post-operative nursing interventions were summarized, and vital signs, changes of biochemical markers and the occurrence of postoperative complications were compared and recorded.Results:77 patients were classified according to Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM), including 34 patients with type A, 18 patients with type B, 21 patients with type C, and 4 patients with type D. There were 68 patients with congenital bile duct dilation and 9 patients without congenital bile duct dialtion. 92 ERCP procedures were performed under general anesthesia, and 91 cases were successful with a success rate of 98.91%. Among these cases, including 7 cases of endoscopic sphincterotomy, 28 cases of endoscopic balloon dilation of the nipple, 22 cases of endoscopic probe dilation, 22 cases of endoscopic stone removal by balloon or basket, 35 cases of endoscopic retrograde biliary stent drainage, 4 cases of endoscopic pancreatic duct drainage, 18 cases of endoscopic nasobiliary drainage, 2 cases of endoscopic nasobiliary drainage, and 14 cases of biliary stent removal. In 77 children with PBM, body temperature, FLACC score, and laboratory-related biochemical indexes including direct bilirubin, serum amylase, ALT, AST and CGT decreased significantly after ERCP, and all the differences were statistically significant (all P value <0.001). The incidence of postoperative complications was 15.38%(14/91), including hyperamylasemia in 9 cases (9.89%) and abdominal pain in 5 cases (5.49%). Conclusions:ERCP is safe and effective in the treatment of abnormal confluence of pancreatic duct in children.

Evaluation on the effect of standardized training of intravenous therapy nursing technology for community nurses / 中国实用护理杂志

Objective:To provide basis for carrying out standardized training courses of intravenous therapy nursing technology for community nurses and improving the level of intravenous therapy for community nurses.Methods:This was a quasi experimental study. From May to July 2020, 260 nurses from 20 community health service institutions in Dalian were investigated with the convenient sampling method and self-designed evaluation scale for venous treatment nursing skills of community nurses and were given standardized training. The changes of venous treatment nursing skills of community nurses before and after training were compared.Results:The scores of theoretical knowledge, skill operation, complication nursing and health education of the intravenous therapy nursing skill evaluation scale for community nurses after training were (15.32 ± 1.67), (18.26 ± 2.46), (19.32 ± 1.57) and (16.33 ± 1.02) points, which were higher than (10.23 ± 2.43), (12.35 ± 3.42), (14.36 ± 2.48) and (12.31 ± 1.47) points before training. The difference was statistically significant ( t values were 1.32-2.46, all P<0.05). After the training, the total score of the evaluation scale of community nurses' intravenous treatment nursing skills was (77.41 ± 1.21)points, which was higher than that before the training (55.38 ± 1.35) points, with a statistically significant difference ( t=2.38, P<0.05). Conclusions:Higher medical institutions should construct venous treatment training group, strengthen the training of community nurses on intravenous therapy, improve the quality of community intravenous therapy services, and promote the better functioning of community health service institutions.

Common problems and case analysis of scientific research design of nursing papers / 中国实用护理杂志

Scientific research design is the premise of scientific research, and also an important concern of the editor in the process of nursing paper review. It plays a vital role in the quality of nursing papers and the recruitment of the editorial department. Aiming at the common problems of scientific research design encountered by the editors during the review of nursing papers, this paper analyzes them from two aspects: the overall unreasonable scientific research design and the unscientific scientific research design process, in combination with cases, in order to provide help for nursing staff in writing papers.

Association of cumulative resting heart rate exposure with rapid renal function decline: a prospective cohort study with 27,564 older adults / 老年心脏病学杂志（英文版）

OBJECTIVE@#To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older.@*METHODS@#In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2 and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m2 or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders.@*RESULTS@#During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD.@*CONCLUSIONS@#The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

The expression and function of PD-L1 in CD133(+) human liver cancer stem-like cells / 中华肿瘤杂志

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and β-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.

Sex Estimation of Medial Aspect of the Ischiopubic Ramus in Adults Based on Deep Learning / 法医学杂志

OBJECTIVES@#To investigate the reliability and accuracy of deep learning technology in automatic sex estimation using the 3D reconstructed images of the computed tomography (CT) from the Chinese Han population.@*METHODS@#The pelvic CT images of 700 individuals (350 males and 350 females) of the Chinese Han population aged 20 to 85 years were collected and reconstructed into 3D virtual skeletal models. The feature region images of the medial aspect of the ischiopubic ramus (MIPR) were intercepted. The Inception v4 was adopted as the image recognition model, and two methods of initial learning and transfer learning were used for training. Eighty percent of the individuals' images were randomly selected as the training and validation dataset, and the remaining were used as the test dataset. The left and right sides of the MIPR images were trained separately and combinedly. Subsequently, the models' performance was evaluated by overall accuracy, female accuracy, male accuracy, etc.@*RESULTS@#When both sides of the MIPR images were trained separately with initial learning, the overall accuracy of the right model was 95.7%, the female accuracy and male accuracy were both 95.7%; the overall accuracy of the left model was 92.1%, the female accuracy was 88.6% and the male accuracy was 95.7%. When the left and right MIPR images were combined to train with initial learning, the overall accuracy of the model was 94.6%, the female accuracy was 92.1% and the male accuracy was 97.1%. When the left and right MIPR images were combined to train with transfer learning, the model achieved an overall accuracy of 95.7%, and the female and male accuracies were both 95.7%.@*CONCLUSIONS@#The use of deep learning model of Inception v4 and transfer learning algorithm to construct a sex estimation model for pelvic MIPR images of Chinese Han population has high accuracy and well generalizability in human remains, which can effectively estimate the sex in adults.

A preliminary study on reducing the formation of intra-abdominal hernia and postoperative intestinal obstruction in laparoscopic Bricker operation / 现代泌尿外科杂志

【Objective】 To reduce the incidence of postoperative intestinal obstruction, we tried to improve surgical techniques by closing the cavity formed during radical cystectomy + ileal passage (Bricker) via laparoscopy to prevent the formation of abdominal hernia. 【Methods】 During Oct.2018 and Feb.2022, 41 patients were involved (conventional group). After standard laparoscopic radical cystectomy + pelvic lymphadenectomy, the ileum channel was established. The right medial retroperitoneum was sutured to cover the mesothelium and end of the ileum channel under open operation or endoscope. The space between the ureter and mesothelium of the ileum channel was sealed, and the end of the ileum channel and both ureters were externalized. During Feb.2022 and Dec.2022, 15 patients were involved (modified group). The right inner and outer lateral peritoneums below the ileal conduit were sutured to "bottom out" the gap between the ileal conduit and the right abdominal wall in addition to standard procedures. The recovery of intestinal function and incidence of bowel obstruction were compared between the two groups. 【Results】 In the conventional group, the intestinal function recovered within 2 to 6 days after surgery, with a median ventilation time of 3 days. Intestinal obstruction occurred in 3 patients, 2 of whom improved after conservative treatment while 1 underwent surgical exploration after ineffective conservative therapy. There were no significant differences in the time of discharge and ventilation between the two groups, but no intestinal obstruction occurred in the modified group. 【Conclusion】 Peritoneal externalization at the end of ileal passage can reduce the incidence of intra-abdominal hernia and postoperative intestinal obstruction, which is worthy of clinical application.

Molecular mechanism of artesunate attenuates the release of proinflammatory cytokines from macrophages / 中国临床药理学与治疗学

AIM: Lipopolysaccharide (LPS) on the cell membrane of gram negative bacteria is closely related to the occurrence and development of severe acute pancreatitis (SAP). Local and systemic monocyte / macrophages play an important role in the inflammatory process of SAP. Artesunate (AS) was reported to protect rats with severe acute pancreatitis by reducing the release of proinflammatory cytokines. This study further explored the molecular mechanism of anti-inflammatory effect of AS. METHODS: The release of proinflammatory cytokines in the supernatant were studied by enzyme-linked immunosorbent assay. Then, the mRNA expressions of PI3K-III and its key molecules in signaling pathway were detected by real-time quantitative PCR. Finally, the phosphorylation levels of PI3KIII were detected by Western blot. RESULTS: AS could significantly inhibit the release of proinflammatory cytokines from mouse macrophage induced by LPS. Autophagy inhibitor 3-methyladenine (3-MA) could significantly inhibit the release of TNF-α from mouse macrophages induced by LPS; LPS significantly increased the mRNA expression of PI3KIII and its key molecules in mouse peritoneal macrophages (PMs). Finally, AS could significantly inhibit the increase of PI3K-III phosphorylation induced by LPS in PMs. CONCLUSION: The anti-inflammatory mechanism of AS is closely related to the inhibition of PI3K-III phosphorylation.

Effect of Danzhi Xiaoyaosan on Phosphorylation of Tau Protein in Rats with Alzheimer's Disease Based on PP2A and GSK-3β / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Danzhi Xiaoyaosan on the phosphorylation of tau protein and different sites of glycogen synthase kinase-3β （GSK-3β） and phosphoseryl/suanyl phosphate protein phosphatase 2A （PP2A） in the hippocampus of rats with Alzheimer's disease （AD） and its mechanism. MethodThe rat model of AD was established by injecting okadaic acid into the bilateral hippocampus of 90 male Wistar rats in SPF grades. The rats with successful modeling were selected and randomly divided into model group， aricept group （0.5 mg·kg-1）， and Danzhi Xiaoyaosan high， medium， and low groups （17.55， 8.77， and 4.38 g·kg-1）， and then gavaged for 42 d， once a day. Morris water maze was used to detect the learning and memory ability of rats， Nissl's staining was used to observe the morphological structure of neurons in the hippocampus， and Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of tau protein， GSK-3β， and PP2A. Western blot was used to determine the protein expression levels of tau protein， GSK-3β， and PP2A. ResultAs compared with the control group， the learning and memory abilities of the rats in the model group were significantly decreased （P<0.01）， and the hippocampal CA3 region cells had abnormal structure， disorderly arrangement， and decreased number. The expression levels of GSK-3β mRNA， GSK-3β， p-GSK-3β-Tyr216， p-PP2A， and p-tau were increased in the model group as compared with the control group （P<0.01）， and those of p-GSK-3β-Ser9 and PP2A decreased significantly （P<0.01）. As compared with the model group， the learning and memory ability of the Aricept group and the Danzhi Xiaoyaosan groups were improved （P<0.05， P<0.01）， and the cell morphology and the number of hippocampal CA3 regions were better. The mRNA expression levels of PP2A and tau in the Aricept group were significantly up-regulated （P<0.05）， the mRNA expression level of GSK-3β was significantly down-regulated （P<0.01）， and the protein expression levels of GSK-3β， p-GSK-3β-Tyr216， and p-PP2A were down-regulated （P<0.05， P<0.01）， and the protein expression level of PP2A was significantly up-regulated （P<0.01）. As compared with the model group， the mRNA expression level of PP2A in the high-dose Danzhi Xiaoyaosan group was significantly up-regulated （P<0.01）， and that of GSK-3β was significantly down-regulated （P<0.01）， whereas the protein expression levels of p-PP2A， p-GSK-3β-Tyr216， and p-tau were down-regulated （P<0.05， P<0.01）， and the protein expression level of PP2A was significantly up-regulated （P<0.01）. As compared with the model group， the mRNA expression level of GSK-3β was significantly down-regulated in the medium-dose Danzhi Xiaoyaosan group （P<0.01）， the protein expression levels of GSK-3β， p-GSK-3β-Tyr216， and p-tau were down-regulated （P<0.05， P<0.01）， and the protein expression level of PP2A was significantly up-regulated （P<0.01）. As compared with the model group， the mRNA expression level of PP2A was significantly up-regulated in the low-dose Danzhi Xiaoyaosan group （P<0.01）， and that of GSK-3β was significantly down-regulated （P<0.01）， whereas the protein expression levels of GSK-3β and p-GSK-3β-Tyr216 were down-regulated （P<0.05， P<0.01）， and those of p-GSK-3β-Ser9 and PP2A were significantly up-regulated （P<0.01）. ConclusionDanzhi Xiaoyaosan can improve the learning and memory ability of rats with AD， and its mechanism may be related to the regulation of the activities of GSK-3β and PP2A protein-related sites and the phosphorylation of tau protein.

Application of Worst lacrimal probe combined with modified lacrimal duct threading intubation in anastomosis of complex canalicular laceration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the application value of Worst lacrimal probe combined with modified lacrimal duct intubation in anastomosis of complex canalicular laceration.METHODS: Retrospective study. A total of 68 cases(68 eyes)with complex traumatic canalicular laceration treated in the ophthalmology department of the Second Affiliated Hospital of Zunyi Medical University from March 1, 2019 to March 31, 2021 were selected. They were divided into two groups according to the surgical methods, with 36 patients(36 eyes)who were treated with the Worst lacrimal probe to find the broken end of lacrimal duct combined with improved lacrimal duct threading intubation in group A, and 32 patients(32 eyes)who were treated with microscope to find the broken end of lacrimal duct and two-way intubation anastomosis canaliculus intubation in group B. The clinical efficacy, success rate of intraoperative search for the broken end of lacrimal duct, searching time, operation time, the degree of pain, postoperative ocular foreign body sensation and complications were compared between the two groups.RESULTS: The total effective rate of clinical efficacy in patients of group A was higher than that in group B(94% vs. 38%), the success rate of intraoperative search for broken end of lacrimal duct was higher than that in group B(100% vs. 47%), the searching time and operation time were shorter than those in group B, and the score of pain degree was lower than that in group B(all P&#x0026;#x003C;0.05). The postoperative follow-up for 6mo-1a showed that the ocular foreign body sensation score, the incidence of lacrimal punctum rupture and morphological change, and the degree of tear overflow in group A were all lower than those in group B(all P&#x0026;#x003C;0.05).CONCLUSION: Worst lacrimal probe combined with modified lacrimal duct intubation for the treatment of complex traumatic canalicular laceration can find the broken end of lacrimal duct more accurately, shorten the operation time, reduce the pain and foreign body sensation of patients, improve clinical efficacy and reduce the incidence of complications.