Efficacy and safety of switching to flumatinib in patients with chronic myeloid leukemia who have not achieved optimal response or are intolerant to TKI treatment / 陆军军医大学学报

Objective To observe the efficacy and safety of flumatinib conversion in chronic myelogenous leukemia-chronicphase(CML-CP)patients with suboptimal TKI response or intolerance.Methods Patients who did not have the best response or intolerance to first-line imatinib,dasatinib,and nilotinib and switched to flumatinib(600 mg/d)from February 2020 to August 2022 were collected from 5 hospitals from Chongqing and affiliated hospitals of North Sichuan Medical College.The efficacy and safety of flumatinib were observed.The optimal response rate,major molecular response(MMR),cumulative complete cytogenetic response(CCyR)rate,cumulative MMR rate,cumulative deep molecular response(DMR),progression-free survival(PFS),event-free survival(EFS)and adverse reactions in 3,6 and 12 months after treatment were observed and analyzed.Results A total of 100 patients with CML-CP were enrolled,with a median follow-up of 18(3～36)months.The optimal response rate was 92.6％(88/95),94.4％(85/90)and 92.9％(79/85)respectively,at 3,6 and 12 months after treatment.Till August 20,2023,the cumulative CCyR and MMR rate was 98.0％(98/100)and 81.9％(77/94),respectively,the median time to reach CCyR and MMR was 3 months,and cumulative DMR rate was 51.0％(51/100).PFS rate was 100.0％(100/100)and 1-year EFS rate was 85.6％(75/90).The most common non-hematologic adverse reactions of flumatinib were diarrhea and abdominal pain(7.0％),followed by renal dysfunction(6.0％)and musculoskeletal pain(2.0％).The main hematologic adverse reactions were thrombocytopenia(12.0％),anemia(6.0％)and leukopenia(2.0％).Conclusion Flumatinib has better MMR and DMR and is well tolerated in CML-CP patients with TKI resistance or intolerance.

Expression of serum miR-145 and miR-195 in OSCC patients and their relationship with cervical lymph node metastasis / 国际检验医学杂志

Objective To analyze the expression of serum microRNA(miR)-145 and miR-195 in patients with oral squamous cell carcinoma(OSCC)and their relationship with cervical lymph node metastasis.Methods A total of 102 patients diagnosed with OSCC in the hospital from January 2020 to June 2022 were selected as OSCC group.Clinicopathological parameters of OSCC patients were collected and sorted.According to whether cervical lymph node metastasis occurred,the patients were divided into a cervical lymph node me-tastasis group(43 cases)and a non-cervical lymph node metastasis group(59 cases).In the same period,79 patients with precancerous lesion were selected as the precancerous lesion group,and 86 healthy subjects with-out oral disease were selected as the healthy control group.Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of serum miR-145 and miR-195.The evaluation value of relative expression levels of serum miR-145 and miR-195 in cervical lymph node metastasis in OSCC patients was examined by receiver operating characteristic curve analysis.Results The relative expression lev-els of serum miR-145 and miR-195 in OSCC group were lower than those in precancerous lesion group and healthy control group,and the difference was statistically significant(P＜0.05).The relative expression levels of serum miR-145 and miR-195 in precancerous lesion group were lower than those in healthy control group,and the difference was statistically significant(P＜0.05).The relative expression levels of serum miR-145 and miR-195 in OSCC patients with low tumor differentiation and TNM stage Ⅲ+Ⅳ were lower than those in OSCC patients with medium/high tumor differentiation and TNM stage Ⅰ+Ⅱ,with statistical significance(P＜0.05).The relative expression levels of serum miR-145 and miR-195 in cervical lymph node metastasis group were lower than those in non-cervical lymph node metastasis group,and the difference was statistically significant(P＜0.05).The relative expression levels of serum miR-145 and miR-195 were 0.840(95％CI:0.765-0.915),0.832(95％CI:0.754-0.910)and 0.898(95％CI:0.754-0.910)of cervical lymph node metastasis in OSCC patients respectively.The specificity was 79.1％,88.4％and 77.5％,and the sensitivity was 74.6％,67.8％and 87.4％,respectively.Conclusion Serum miR-145 and miR-195 are low expressed in OSCC patients,and are related to cervical lymph node metastasis,tumor differentiation,and TNM stage in OSCC patients,which can be used as an important indicator to evaluate cervical lymph node metastasis in OS-CC patients.

Correlation of KRAS Gene 3'UTR Polymorphisms with Cervical Cancer and Cervical Intraepithelial Neoplasia in Chinese Han Population in Yunnan Province / 昆明医科大学学报

Objective To investigate the correlation between rs712 and rs7973450 located at the 3'UTR region of the KRAS gene and the risk of cervical cancer(CC)and cervical intraepithelial neoplasia(CIN)in Chinese Han population in Yunnan province.Methods A total of 2405 individuals(461 subjects with CIN,961 subjects with CC and 983 healthy controls)were enrolled.The SNPs were genotyped used TaqMan assay and the correlation of these SNPs with CIN and CC was analyzed.Results The A allele of rs7973450 might be a protective factor for the occurrence of CIN(P = 0.004,OR= 0.651,95%CI 0.487～0.871)and CC(P = 7.00×10-4,OR= 0.667,95%CI 0.529～0.844).There was no significant difference in allelic and genotypic distribution of rs712 among CIN,CC and Control groups(P>0.017).The haplotype assay showed thatrs712A-rs7973450G was associated with increased risk of CIN(P = 4.00×10-4;OR= 1.714,95%CI 1.269～2.314)and CC(P = 3.84×10-5,OR= 1.667,95%CI 1.305～2.131).While haplotype rs712A-rs7973450A was associated with a lower risk of CC(P = 0.012,OR= 0.790,95%CI 0.658～0.950).Conclusion The A allele of rs7973450 in 3'UTR of KRAS gene might be the protective factor for the occurrence of CIN and CC in a Chinese Han population in Yunnan province.

Analysis of HPV infection and genotype distribution among 1 658 male reproductive health outpatients / 复旦学报（医学版）

Objective To investigate the human papillomavirus(HPV)infection and genotype distribution characteristics among male reproductive health outpatients,and to compare the differences among different age groups of outpatients.Methods A total of 1 658 males,visited in the Affiliated Hospital of Shanghai Institute of Planned Parenthood Research from 2018 to 2022,were selected and 23 HPV genotypes were detected by PCR-reverse dot hybridization.Results Among the 1 658 subjects,the overall HPV infection rate was 22.50%.Single infection accounted for 66.76%,which was the main infection type.HPV infection among different age groups were statistically significant(P<0.001),with HPV infection of 16.83%,22.87%,34.63%,and 29.35%for 18-30,31-40,41-50,and≥51 years,respectively.The top 5 high risk HPV genotypes were HPV52(3.56%),HPV16(3.26%),HPV39(2.41%),HPV51(2.17%),HPV58(2.17%),and the top 1 low risk HPV genotype was HPV81(2.90%).The proportions of infected individuals in this study that could be completely covered by bivalent,quadrivalent,and nine-valent HPV vaccines were 7.77%,12.33%,and 26.27%,respectively.Conclusion The predominant infection type among male reproductive health outpatients was single infection type.HPV 52,16,39,51 and 58 were the most common high risk genotypes,while HPV 81 was the most common low risk genotype.Individuals aged 41-50 years had the highest HPV infection rate.

Relationship between blood indicators and course of nontraumatic osteonecrosis of femoral head in different stages:multiple logistic regression analysis / 中国组织工程研究

BACKGROUND:Up to now,there is no literature on the relationship between blood laboratory tests and the course of nontraumatic osteonecrosis of femoral head in different stages.It is necessary to further explore and analyze so as to better clarify the influencing factors of nontraumatic osteonecrosis of femoral head. OBJECTIVE:To analyze the relationship between blood laboratory indicators and the course of nontraumatic osteonecrosis of the femoral head by the Association Research Circulation Osseous(ARCO),thus exploring the influencing factors of blood laboratory indicators on the course of nontraumatic osteonecrosis of the femoral head. METHODS:This study used a retrospective study design.A total of 2 103 patients with osteonecrosis of the femoral head were retrieved from Wangjing Hospital of China Academy of Chinese Medical Sciences database,and 1 075 patients with nontraumatic osteonecrosis of the femoral head were ultimately included based on inclusion and exclusion criteria.Patient age,gender,body mass index,and blood laboratory test results were collected.Blood laboratory tests included low-density lipoprotein,total cholesterol,triglycerides,high-density lipoprotein,apolipoprotein β,apolipoprotein α1,uric acid,total protein quantitative,alkaline phosphatase,activated partial thromboplastin time,prothrombin time,prothrombin time International Normalized Ratio,prothrombin time activity,fibrinogen quantitative,coagulation time of thrombin,D-dimer,total iron binding capacity,and platelet count.The indicators of patients with different age groups and different ARCO stages were compared,and multiple Logistic regression analysis was applied to explore the influencing factors of ARCO stages in osteonecrosis of the femoral head. RESULTS AND CONCLUSION:(1)There were statistical differences in total cholesterol,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer among ARCO stages in the young group(P<0.05).Among young patients in ARCO stage II,total cholesterol levels were higher than those in ARCO stage III(P<0.05).Uric acid levels in ARCO stage IV were higher than those in ARCO stage II and III(P<0.05).Prothrombin time and prothrombin time International Normalized Ratio were shorter in ARCO stage IV and II than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stage III and IV than in ARCO stage II(P<0.05).(2)There were statistically significant differences in high-density lipoprotein,coagulation time of thrombin,and D-dimer among ARCO stages in the middle-aged group(P<0.05).Among middle-aged patients in ARCO stage IV,high-density lipoprotein levels were higher than those in ARCO stages II and III(P<0.05).Coagulation time of thrombin was shorter in ARCO stage IV than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stages IV than in ARCO stages II and III(P<0.05).(3)The uric acid,activated partial thromboplastin time,D-dimer,and platelet count in the elderly group showed statistically significant differences(P<0.05).The uric acid level in ARCO stage IV was higher than that in ARCO stage II and III patients in the elderly group(P<0.05),while the activated prothrombin time in ARCO stage II patients was shorter than that in ARCO stage III patients in the elderly group(P<0.05).The D-dimer level in ARCO stage III and IV patients was higher than that in ARCO stage II patients in the elderly group(P<0.05).The platelet count in ARCO stage IV was lower than that in ARCO stage III patients in the elderly group(P<0.05).(4)Multiple logistic regression analysis showed that total cholesterol and platelet count may be protective factors for course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and young and middle age may be risk factors for course of nontraumatic osteonecrosis of the femoral head.(5)It is indicated that total cholesterol,high-density lipoprotein,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer are statistically significant among patients with different ARCO stages.Total cholesterol and platelet count may be protective factors for the course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and middle-aged and young age groups may be hazard factors for the course of nontraumatic osteonecrosis of the femoral head.

PIEZO1 Channel is Involved in Electric Field Guided Cell Migration / 生物化学与生物物理进展

ObjectiveDisruption of epithelial layer may instantaneously induce the generation of endogenous electric fields, which was proved to play an important role in guiding the cell migration and promoting wound healing. PIEZO1 is a kind of mechanic sensitive channel, may be regulated by voltage, is proved to involve in chemotactic migration of cells and play an important role in the process of wound healing. In this paper, the role of PIEZO1 and its downstream proteins FAK and integrin β1 in the electric field guided cell migration were investigated by HaCaT cells (human immortalized keratinocyte). MethodsCell migration was tracked by Living Cell Imaging System in directed current (DC) electric field (EF). Inhibitors and RNAi techniques were applied to study the function of PIEZO1 and other related proteins in electric fields. Western blot was used to detect the expression and phosphorylation levels of integrin β1 and FAK in electric field guided migration under EF stimulation. ResultsPiezo1 RNAi as well as Ruthenium red and GsMTx4 treatment all significantly inhibited the electrotaxis of HaCaT cells. Electric field stimulation with GsMTx4 treatment alone increased FAK phosphorylation level and the expression of integrin β1. Electric field promoted the expression level of integrin β1 and the phosphorylation level of FAK. Inhibiting the expression of PIEZO1 by RNAi significantly attenuated the phosphorylation level of FAK under EF stimulation. Inhibition of integrin β1 and FAK by inhibitor significantly decrease the electric field guided cell migration. ConclusionPIEZO1 as well as integrin β1 and FAK are involved in the electric field guided cell migration of HaCaT cells. Electric field signals regulate the expression of integrin β1 and the activation of FAK through PIEZO1-mediated signal pathway to orchestrate cell migration.

Ligustilide delays senescence of auditory cortex in mice by inhibiting ferritinophagy / 中国药理学通报

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Three 2,3-diketoquinoxaline alkaloids with hepatoprotective activity from Heterosmilax yunnanensis / 药学学报

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Comparison of the effectiveness of different endoscopic retrograde cholangiopancreatography complexity scales in the training of endoscopists / 中国内镜杂志

Objective To explore the utility of different endoscopic retrograde cholangiopancreatography(ERCP)complexity scales in the training of endoscopists.Methods Clinical data of 237 patients treated by ERCP completed by trainee physicians at two hospitals in Eastern China from February 2022 to February 2023 were prospectively collected.All ERCP cases were classified using previously proposed complexity grading scales,including the American Society of Gastrointestinal Endoscopy(ASGE),Morriston and HOUSE grading scales,compared with the hepatopancreatic ampulla features classification.Successful intubation,successful surgical treatment and complication rates within 48 h were recorded.Results Within each grading,subgroups were divided according to severity,and the comparison of intubation success rates between subgroups in the 3 different grades showed statistically significant differences(P = 0.000).The treatment success rate and intubation success rate had similar findings(P = 0.000).There was no correlation between the complication rate and ASGE grading(P = 0.361),Morriston grading(P = 0.332),and HOUSE grading(P = 0.586).When only cases with primitive papillae were considered,the intubation success rate depended on the complexity grading after the newly added classification of hepatopancreatic ampulla features.In the ASGE group,the success rate of intubation was compared between different subgroups,and the difference was statistically significant(P = 0.004);in the Morriston group,the success rate of intubation was compared between different subgroups,and the success rate of intubation was statistically significant(P = 0.002);in the HOUSE group,the success rate of intubation was compared between different subgroups,and the difference was statistically significant(P = 0.000);In the hepatopancreatic ampulla characteristics group,the difference in intubation success rate was statistically significant when compared between different subgroups(P = 0.000).Similar findings were also found for treatment success rate and intubation success rate(P = 0.000).There was no correlation between the complication rate and ASGE group(P = 0.586),Morriston group(P = 0.443),HOUSE group(P = 0.306),and hepatopancreatic ampulla characteristics group(P = 0.350).Conclusion The use of hepatopancreatic ampulla features as a classification of biliary cannulation complexity is feasible and could be an alternative or additional means of predicting successful biliary cannulation and surgical treatment success and could be used in the future to assess endoscopist training and learning progress and technical standards.

Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population

Abstract Background In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. Methods SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. Results There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). Conclusions Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA. Key Points Genetic variants of WNT9A were associated with the incidence and severity of TOA. Allele G of rs11588850 was associated with an increased transcriptional activity of WNT9A promoter. Allele G of rs11588850 may add to the risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

Establishment and validation of a nomogram for predicting prognosis of gastric neuroendocrine neoplasms based on data from 490 cases in a single center / 南方医科大学学报

OBJECTIVE@#To develop and validate a nomogram for predicting outcomes of patients with gastric neuroendocrine neoplasms (G-NENs).@*METHODS@#We retrospectively collected the clinical data from 490 patients with the diagnosis of G-NEN at our medical center from 2000 to 2021. Log-rank test was used to analyze the overall survival (OS) of the patients. The independent risk factors affecting the prognosis of G-NEN were identified by Cox regression analysis to construct the prognostic nomogram, whose performance was evaluated using the C-index, receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, DCA, and AUDC.@*RESULTS@#Among the 490 G-NEN patients (mean age of 58.6±10.92 years, including 346 male and 144 female patients), 130 (26.5%) had NET G1, 54 (11.0%) had NET G2, 206 (42.0%) had NEC, and 100 (20.5%) had MiNEN. None of the patients had NET G3. The numbers of patients in stage Ⅰ-Ⅳ were 222 (45.3%), 75 (15.3%), 130 (26.5%), and 63 (12.9%), respectively. Univariate and multivariate analyses identified age, pathological grade, tumor location, depth of invasion, lymph node metastasis, distant metastasis, and F-NLR as independent risk factors affecting the survival of the patients (P < 0.05). The C-index of the prognostic nomogram was 0.829 (95% CI: 0.800-0.858), and its AUC for predicting 1-, 3- and 5-year OS were 0.883, 0.895 and 0.944, respectively. The calibration curve confirmed a good consistency between the model prediction results and the actual observations. For predicting 1-year, 3-year and 5-year OS, the TNM staging system and the nomogram had AUC of 0.033 vs 0.0218, 0.191 vs 0.148, and 0.248 vs 0.197, respectively, suggesting higher net benefit and better clinical utility of the nomogram.@*CONCLUSION@#The prognostic nomogram established in this study has good predictive performance and clinical value to facilitate prognostic evaluation of individual patients with G-NEN.

Associations of TNF-RII rs1061622 With Post-Traumatic Stress Disorder and Their Interplays on Serum Lipids Levels in Adolescents

Objective@#To verify effects of rs1061622 at tumor necrosis factor-α receptor II (TNF-RII) gene (TNF-RII) on post-traumatic stress disorder (PTSD) and its interactive effects with PTSD on serum lipids levels in adolescents. @*Methods@#PTSD was measured by PTSD Checklist-Civilian Version (PCL-C) in 699 adolescent survivors at 6 months after Wenchuan earthquake in China. A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for TNF-RII rs1061622 genotyping followed by verification using DNA sequencing. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were tested using routine methods. @*Results@#G (deoxyguanine) allele carriers had higher PCL-C scores than TT (deoxythymidine) homozygotes in female subjects. Female adolescents had higher PCL-C scores than male subjects in TT homozygotes. Predictors of PTSD prevalence and severity were different between G allele carriers and TT homozygotes. Subjects with PTSD had lower TG, TG/HDL-C, TC/HDL-C, and higher HDL-C than adolescents without PTSD in male G allele carriers. G allele carriers had higher TG/HDL-C and TC/HDL-C than TT homozygotes in male adolescents without PTSD, and lower TG and TG/HDL-C in male PTSD patients. G allele carriers had higher TG than TT homozygotes only in female adolescents without PTSD. @*Conclusion@#These results suggest reciprocal actions of TNF-RII rs1061622 with other factors on PTSD severity, interplays of TNF-RII rs1061622 with PTSD on serum lipid levels, and novel treatment strategies for PTSD and comorbidities of PTSD with hyperlipidemia among adolescents with different genetic backgrounds of TNF-RII rs1061622 after experiencing traumatic events.

Analyzing the current status of newly diagnosed occupational pneumoconiosis patients in Zhangdian District of Zibo City / 中国职业医学

Objective To analyze the distribution, survival conditions, and medical support of newly diagnosed occupational pneumoconiosis (hereinafter referred to as pneumoconiosis) patients in Zhangdian District, Zibo City. Methods A total of 1 189 newly diagnosed pneumoconiosis patients in Zhangdian District from 1956 to 2019 were selected as the study subjects using retrospective method. Data of their age of onset, years of occupational exposure, category of working industry, type of pneumoconiosis, and status of medical support was collected and analyzed. Results The median and the 25th-75th percentiles ［M (P25, P75)］ of the age of onset were 51.8 (45.5, 56.1) years, and the mortality was 37.0%. The majority of pneumoconiosis cases were silicosis (45.2%) and coal workers' pneumoconiosis (39.8%). The highest prevalence of pneumoconiosis was in the coal mining and washing industry (42.4%), followed by manufacturing (33.4%). Pneumoconiosis patients in stage Ⅰ,Ⅱ, and Ⅲ accounted for 89.1%, 8.7%, and 2.2%, respectively. The M (P25, P75) of the length of work exposed to dust were 24.1 (16.5, 29.9) years.The higher stage of pneumoconiosis the shorter of the length of work exposed to dust among these pneumoconiosis patients(all P<0.05). The overall survival rate, the 5-year survival rate and the 10-year survival rate of these pneumoconiosis patients were 63.0%, 92.3% and 85.9%, respectively. Among the 749 surviving cases, 60.8% were aged 60.0 to <80.0 years. In terms of social security, 100.0% surviving cases enjoyed basic medical insurance, meanwhile, 96.1% and 81.8% patients were covered by major medical insurances and occupational injury insurances, respectively. The M (P25, P75) of age at death were 73.1 (64.0, 77.1) years. The main causes of death were respiratory diseases (59.3%) and malignant tumors (20.4%). Conclusion The prevalent types of pneumoconiosis in Zhangdian District, Zibo City, are coal workers' pneumoconiosis and silicosis. Medical support and assistance are relatively limited. The pneumoconiosis prevention and control focus should be on silicosis and coal workers' pneumoconiosis, particularly in the manufacturing industry.

Clinical diagnosis and treatment of multiple pulmonary nodules / 中华肿瘤杂志

CT screening has markedly reduced the lung cancer mortality in high-risk population and increased the detection of early-stage pulmonary neoplasms, including multiple pulmonary nodules, especially those with a ground-glass appearance on CT. Multiple primary lung cancer (MPLC) constitutes a specific subtype of lung cancer with indolent biological behaviors, which is predominantly early-stage adenocarcinoma. Although MPLC progresses slowly with rare lymphatic metastasis, existence of synchronous lesions and distributed location of these nodules still pose difficulty for the management of such patients. One single operation is usually insufficient to eradicate all neoplastic lesions, whereas repeated surgical procedures bring about another dilemma: whether clinical benefits of surgical treatment outweigh loss of pulmonary function following multiple operations. Therefore, despite the anxiety for treatment among MPLC patients, whether and how to treat the patient should be assessed meticulously. Currently there is a heated discussion upon the timing of clinical intervention, operation mode and the application of local therapy in MPLC. Based on clinical experience of our multiple disciplinary team, we have summarized and commented on the evaluation, surgical treatment, non-surgical local treatment, targeted therapy and immunotherapy of MPLC in this article to provide further insight into this field.

Association between exposure patterns of adverse childhood experiences and anxiety symptom trajectories in medical college students / 中华预防医学杂志

Objective: To analyze the association between exposure patterns of adverse childhood experiences (ACEs) and anxiety symptom trajectories in medical college students. Methods: A survey was conducted on first-year students from Anhui Medical College and Anqing Medical College, using the Childhood Abuse Questionnaire, Family Disability Questionnaire, Childhood Adverse Social Experience Item, and Anxiety Self Rating Scale. The baseline survey was conducted from November to December 2019, and two follow-up visits were conducted once every six months until November to December 2020. The latent class analysis (LCA) was used to analyze the exposure patterns of ACEs. The latent class growth analysis (LCGA) was used to analyze the development trajectory of anxiety symptoms. The multiple logistic regression model was used to analyze the correlation between different exposure patterns of ACEs and the trajectory of anxiety symptom trajectories. Results: A total of 3 662 college students aged (19.2±1.0) were surveyed. The LCA showed that the exposure patterns of ACEs could be divided into the "high ACEs" group (13.4%), "high neglect/emotional abuse" group (25.7%), "high family dysfunction" group (6.9%), "high neglect" group (27.1%), and "low ACEs" group (26.3%). The LCGA divided anxiety trajectories into four groups: "high anxiety decline" (7.1%),"anxiety increase "(4.1%), "moderate anxiety"(52.9%), and "low anxiety"(35.9%). Using the low ACEs group as a reference group, compared with the low anxiety trajectory, the high ACEs group, high neglect/emotional abuse group, high family dysfunction group, high neglect group, and medium to high-level anxiety trajectory were all associated with an increased risk (P<0.05). Conclusion: There is heterogeneity in ACEs exposure patterns among medical college students, and ACEs exposure patterns are important influencing factors for anxiety symptom trajectories.

The beginnings and evolution of a pancreatic surgeon: a technical morphological analysis in first 5 years / 中华外科杂志

Objective: To explore the development of the pancreatic surgeon technique in a high-volume center. Methods: A total of 284 cases receiving pancreatic surgery by a single surgeon from June 2015 to December 2020 were retrospectively included in this study. The clinical characteristics and perioperative medical history were extracted from the medical record system of Zhongshan Hospital,Fudan University. Among these patients,there were 140 males and 144 females with an age (M (IQR)) of 61.0 (16.8) years(range: 15 to 85 years). The "back-to-back" pancreatic- jejunal anastomosis procedure was used to anastomose the end of the pancreas stump and the jejunal wall. Thirty days after discharge,the patients were followed by outpatient follow-up or telephone interviews. The difference between categorical variables was analyzed by the Chi-square test or the CMH chi-square test. The statistical differences for the quantitative data were analyzed using one-way analysis of variance or Kruskal-Wallis H test and further analyzed using the LSD test or the Nemenyi test,respectively. Results: Intraoperative blood loss in pancreaticoduodenectomy between 2015 and 2020 were 300,100(100),100(100),100(0),100(200) and 150 (200) ml,respectively. Intraoperative blood loss in distal pancreatectomy was 250 (375),100 (50),50 (65), 50 (80),50 (50),and 50 (100) ml,respectively. Intraoperative blood loss did not show statistical differences in the same operative procedure between each year. The operative time for pancreaticoduodenectomy was respectively 4.5,5.0(2.0),5.5(0.8),5.0(1.3),5.0(3.3) and 5.0(1.0) hours in each year from 2015 to 2020,no statistical differences were found between each group. The operating time of the distal pancreatectomy was 3.8 (0.9),3.0 (1.5),3.0 (1.8),2.0 (1.1),2.0 (1.5) and 3.0(2.0) hours in each year,the operating time was obviously shorter in 2018 compared to 2015 (P=0.026) and 2020 (P=0.041). The median hospital stay in 2020 for distal pancreatectomy was 3 days shorter than that in 2019. The overall incidence of postoperative pancreatic fistula gradually decreased,with a incident rate of 50.0%,36.8%,31.0%,25.9%,21.1% and 14.8% in each year. During this period,in a total of 3,6,4,2,0 and 20 cases received laparoscopic operations in each year. The incidence of clinically relevant pancreatic fistula (grade B and C) gradually decreased,the incident rates were 0,4.8%,7.1%,3.4%,4.3% and 1.4%,respectively. Two cases had postoperative abdominal bleeding and received unscheduled reoperation. The overall rate of unscheduled reoperation was 0.7%. A patient died within 30 days after the operation and the overall perioperative mortality was 0.4%. Conclusion: The surgical training of a high-volume center can ensure a high starting point in the initial stage and steady progress of pancreatic surgeons,to ensure the safety of pancreatic surgery.

Analysis of clinicopathological characteristics, therapeutic strategy and prognosis of 501 patients with gastric neuroendocrine neoplasms attending a single center / 中华胃肠外科杂志

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.

Transanal drainage tube for prevention of anastomotic leak after anterior resection for rectal cancer: a meta-analysis / 中华胃肠外科杂志

Objective: To assess the effectiveness of transanal drainage tube (TDT) in reducing the incidence of anastomotic leak following anterior resection in patients with rectal cancer. Methods: We conducted a systematic search for relevant studies published from inception to October 2022 across multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. Meta-analysis was performed using Review Manager 5.4 software. The primary outcomes included total incidence of anastomotic leak, grade B and C anastomotic leak rates, reoperation rate, anastomotic bleeding rate, and overall complication rate. Results: Three randomized controlled trials involving 1115 patients (559 patients in the TDT group and 556 in the non-TDT group) were included. Meta-analysis showed that the total incidences of anastomotic leak and of grade B anastomotic leak were 5.5% (31/559) and 4.5% (25/559), respectively, in the TDT group and 7.9% (44/556) and 3.8% (21/556), respectively, in the non-TDT group. These differences are not statistically significant (P=0.120, P=0.560, respectively). Compared with the non-TDT group, the TDT group had a lower incidence of grade C anastomotic leak (1.6% [7/559] vs. 4.5% [25/556]) and reoperation rate (0.9% [5/559] vs. 4.3% [24/556]), but a higher incidence of anastomotic bleeding (8.2% [23/279] vs. 3.6% [10/276]). These differences were statistically significant (P=0.003, P=0.001, P=0.030, respectively). The overall complication rate was 26.5%(74/279) in the TDT group and 27.2% (75/276) in the non-TDT group. These differences are not statistically significant (P=0.860). Conclusions: TDT did not significantly reduce the total incidence of anastomotic leak but may have potential clinical benefits in preventing grade C anastomotic leak. Notably, placement of TDT may increase the anastomotic bleeding rate.

Brief introduction of Qilu modern acupuncture methods / 中国针灸

Qilu acupuncture and moxibustion has promoted the formation and development of traditional Chinese medicine, which has a special historical position. By systematically collecting, sorting out and summarizing the characteristic acupuncture methods and academic ideas of several Qilu acupuncturists since the founding of the People's Republic of China, the understanding of the advantages and characteristics of Qilu modern acupuncture methods is deepened, aiming to exploring the inheritance and development pattern of Qilu acupuncture methods in the new era.

Overview and reflection on the development of the first batch of the inheritance studios of acupuncture and moxibustion academic schools / 中国针灸

The development status of the first 11 inheritance studios of acupuncture and moxibustion academic schools is summarized. Aiming at the current problems, it is suggested to establish qualitative and quantitative evaluation standards and establish a fair and reasonable evaluation system, build a systematic scientific theory and excavate the inherent laws of the schools, implement standardized management of the schools and protect the personalized characteristics of the schools, open outpatient clinic of acupuncture and moxibustion schools and promote the characteristic diagnosis and treatment technology, to promote the inheritance and development of acupuncture and moxibustion academic schools.