[摘 要] 目的：探究浸润性复层产生黏液的复层上皮癌（ISMC）的临床组织及分子病理特征。方法： 回顾性分析2018年1月至2024年4月间安徽医科大学安庆医学中心/安庆市立医院及皖南医学院第一附属医院/弋矶山医院的病理数据库的11例ISMC和4例产生黏液的复层上皮内病变（SMILE）的临床病理资料、免疫组化、阿利新蓝（AB）/过碘酸雪夫（PAS）染色、分子学检测及PD-L1表达情况。结果：ISMC患者多表现为阴道不规则流血。细胞质内含有黏液的细胞呈复层排列，周围呈栅栏状，肿瘤细胞可呈印戒样或胞质透明。ISMC不仅存在单纯型，也可呈混合型。ISMC具有高侵袭性的生物学特性。CK7、p16，p40和（或）p63表达呈癌巢周栅栏状阳性或局灶表达。AB/PAS染色阳性。人乳头状病毒（HPV）检测结果：ISMC中HPV16/18阳性（1/4），术前检测出HPV16/18阳性（4/6）；SMILE组织中HPV阴性。ISMC均表达PD-L1。成功随访8例ISMC患者，时间4~39个月（平均20.50月），4例SMILE患者，时间1~25个月（平均8.25月），随访患者均存活，1例ISMC术后出现多脏器转移。结论：ISMC具有独特的形态学特征及免疫表型，表现为高侵袭性和不良预后。所有ISMC均呈PD-L1阳性，提示所有患者均可从PD-L1免疫治疗中获益。

This paper summarized Professor XU Jingfan's clinical experience of using Zisu （Perillafrutescens） for the treatment of spleen and stomach diseases. According to the disease characteristics， Professor XU flexibly selected the different parts of Zisu. It is believed that the leaf of Zisu is good at dispersing， dredging qi movement， and good at treating external contraction as well as internal damage due to depression or stagnation， and being effective in relieving abdominal lumps and fullness with vomiting； its stem is good at widering chest and diaphragm， smoothing qi and the middle， and dredging the twelve meridians， which can treat qi stagnation， especially suitable for distention and fullness in the midline of body like throat， esophagus， and stomach. Perilla seed is good at depressing qi and eliminating phlegm， loosening bowels to relieve constipation， which can be used in diseases of combined phlegm and qi， and combined treatment of lung and intestines to treat long-term constipation. In clinic， Huanglian （Coptis chinensis）- Zisu leaf is often used as pungent dispersing and bitter descending， promoting qi movement to treat persistent nausea and vomiting； Xiangfu （Cyperi Rhizoma）-Zisu stem is employed as regulating qi to smooth the middle， soothing qi to disperse liver stagnation for various syndromes of qi stagnation； Huomaren （Cannabis Fructus）-Zisu seed is utilized to clear the lungs and benefit qi， and moisten intestines by purgation for chronic constipation. The original ancient formulas are flexibly modified and tailored， so usually modified Banxia Houpo Decoction （半夏厚朴汤） is used to treat plum-stone qi （globus hystericus） and esophageal disorders， while modified Buzhong Yiqi Decoction （补中益气汤） combined with Xiangsu Powder （香苏散） is used to treat gastroptosis， then self-prescribed Jixing Tuxie Formula （急性吐泻方） is used for acute diarrhea， and Xiexie Waizhi Formula （泄泻外治方） is applied for chronic cold-dampness diarrhea.

Objective : To analyze the mediating effect of psychological resilience between occupational stress and job burnout of medical staff, so as to provide the reference for improving job burnout of medical staff. Methods: The front-line medical staff from four tertiary general hospitals in a joint logistics support center were selected as the research objects from April to June 2022 using the convenience sampling method. The data on gender, age, professional title, and working years were collected by a questionnaire survey. Occupational stress, psychological resilience, and job burnout were evaluated using the Job Stressors Scale, the Connor-Davidson Resilience Scale, and the Maslach Burnout Inventory, respectively. The mediating effect of psychological resilience between occupational stress and job burnout was analyzed using the Process procedure, and the significance of the mediating effect was analyzed using the Bootstrap method. Results: A total of 383 people were investigated, among whom 370 were females (96.61%), and 13 were males (3.39%), with a mean age of (28.97±6.56) years. The scores of occupational stress, psychological resilience, and job burnout were (347.17±157.98), (87.18±13.17), and (56.07±17.09) points, respectively. The results of mediating effect analysis showed that occupational stress could directly positively affect job burnout with a direct effect value of 0.061 (95%CI: 0.004-0.119), and it could also indirectly positively affect job burnout through psychological resilience with a mediating effect value of 0.035 (95%CI: 0.002-0.122), and the mediating effect accounted for 57.38% of the total effect. Conclusions Occupational stress can directly or indirectly affect job burnout through psychological resilience. It is suggested to strengthen the mental health training of medical staff to improve psychological resilience and reduce job burnout.

Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.

Objective:To explore the application effect of group guidance based on intelligent communication matrix in patients with type 2 diabetes mellitus (T2DM) .Methods:Using the convenient sampling method, a total of 60 T2DM patients with poor self-management ability who scored less than 19.6 on Summary of Diabetes Self Care Activities (SDSCA) in the Affiliated Chuzhou Hospital of Anhui Medical University were selected as the research objects from May to June 2020. They were randomly divide into the observation group ( n=30) and the control group ( n=30). The observation group was given continuous group guidance based on intelligent communication matrix, while the control group was given routine health guidance. The SDSCA score, body mass index and glycosylated hemoglobin (HbA1c) before and after intervention were compared between the two groups. Results:After intervention, the SDSCA score of the observation group was higher than that of the control group, HbA1c was lower than that of the control group and body mass index was lower than that of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The group guidance based on intelligent communication matrix can improve the self-management level of T2DM patients and reduce their body mass index and HbA1c levels, which has clinical application value.

Purpose: This study identified risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS) through multidimensional analysis of the medical records of patients, aiming to reduce the incidence of NLUTD, improve prognosis, and facilitate rehabilitation. Materials and Methods: In this case-control study, patients with AIS were recruited from two tertiary general hospitals in Shenzhen, China, from March 2021 to October 2023. Patients were divided into NLUTD and non-NLUTD groups based on the presence and absence of NLUTD, respectively. Comparative analysis was performed using the Mann–Whitney U and chi-square tests, with significant variables being included in logistic regression analysis. Results: Of the 652 participants enrolled in this study, 119 participants (18.3%) developed NLUTD. Bivariate analysis showed that 39 of 54 screened factors exhibited a significant correlation (p<0.05) with the incidence of NLUTD after AIS. Significant variables identified through logistic regression analysis included Glasgow coma scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, anemia, aphasia, pneumonia, brainstem involvement, multiple lesions, urine clarity (CLA), random venous blood glucose (GLU) and hemoglobin (HGB) levels, and white blood cell (WBC) count. Conclusions A total of 11 risk factors for NLUTD were identified in this study. This finding provides valuable guidance for reducing the incidence of NLUTD after AIS and improving the quality of life of patients.

Objective To evaluate the effectiveness of exercise for people with Parkinson's disease on sleep quality.Methods Computerized retrieval of PubMed,Web of Science,Embase,the Cochrane Library,CINAHL,CN-KI,WanFang Data,VIP,CBM was conducted to collect randomized controlled trials about the effect of exercise on people with Parkinson's disease from inception to December,2022.There were 2 researchers who independently screened the literature,extracted the data and evaluated the risks of bias in the included studies.Meta-analysis was performed using RevMan 5.4 software.Results A total of 13 studies were included,with 874 patients.The result of meta-analysis show that the overall effect size of exercise intervention on sleep quality for people with Parkin-son's disease is significant(SMD=-0.54,95％CI=[-0.90,-0.19],P＜0.01).Subgroup analysis show that the maxi-mum effect size of intervention frequency is 4-5 times/week(SMD=-0.75);the maximum effect size of exercise intensity is light intensity(SMD=-2.19);the maximum effect size of a single intervention time is 40-55 minutes(SMD=-0.69);the maximum effect size of exercise type is traditional Chinese exercise(SMD=-0.63);the maximum ef-fect size of intervention cycle is 12 weeks(SMD=-0.66).Conclusion Exercise intervention has significantly ef-fects to improve sleep quality on Parkinson's disease patients.It is a more effective way to improve sleep quality by exercising 4-5 times per week,while each exercise lasts about 40-55 min for 12 weeks in Traditional Chinese Medicine exercise with light intensity.

Objective:To analyze the problems and risk factors of the investigator initiated out-of-range trial, propose countermeasures and suggestions, and provide reference for improving project standardization and quality, and preventing research risks.Methods:Through literature analysis and field research, combined with personal work experience, this study sorted and analyzed the problems in the regulation of out-of-range IIT conducted in hospital, and proposed countermeasures.Results:Through analysis, it was found that the current out-of-range IIT trial in China faces 5 problems: imperfect management regulations, incomplete IIT management organizational system in medical institutions, insufficient scientificity of research protocols, insufficient ethical review, and insufficient research funds.Conclusions:Out-of-range IIT is of great significance in promoting pharmaceutical innovation. Standardized management of such projects requires the efforts of regulatory authorities, medical institutions, and ethics committees, as well as the continuous improvement of researchers' awareness and research capabilities to promote the orderly, high-quality, and rapid development of IIT. Based on the above analysis, this article proposed countermeasures and suggestions: at the national level, summarize practical experience from various regions as soon as possible, improve IIT management regulations and technical guidelines; establishing clinical research and design guidance departments in medical institutions and strengthening scientific review; the ethics committee formulates ethical review standards and processes for out-of-range IIT projects to enhance review capabilities; establish a normalized clinical research training mechanism in hospitals; expand and standardize the channels for IIT funding.

Objective To explore the clinical application of ultrasound-guided transabdominal villus and amniocentesis in the prenatal diagnosis of thalassemia,and to find a suitable method for the prenatal diagnosis of thalassemia in Qinzhou.Methods A total of 531 high-risk pregnant women with severe or intermediate thalassemia during single pregnancy who were treated in the Department of Medical Genetics and Prenatal Diagnosis,Qinzhou Maternal and Child Health Hospital from March 2021 to April 2022 were selected for the study.According to different sampling methods,they were divided into control group(amniocentesis,n=415)and study group(transabdominal villus puncture,n=116).The success rate,complication rate of the two groups were compared.Results The success rate of puncture in the control group was 100％,2 cases were aborted within 2 weeks after surgery,17 cases were diagnosed with severe alpha-thalassemia,10 cases with severe β-thalassemia and 64 cases with intermediate thalassemia,48 cases with moderate and severe thalassemia induced labor.The success rate of puncture in the research group was 100％,10 cases were diagnosed with severe alpha-thalassemia,4 cases with severe β-thalassemia and 17 cases with intermediate thalassemia,and 26 cases with moderate severe thalassemia were induced labor.There was no significant difference in puncture success rate and abortion rate between the two methods(P>0.05).Conclusion Both methods are safe and effective.Transabdominal villus sampling can detect fetal thalassemia in early pregnancy,and it is worth promoting and applying in clinical practice.

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.