Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

ObjectiveTo investigate the mortality and years of life lost of pancreatic cancer in Baoshan District of Shanghai，from 2009 to 2021， and to provide scientific evidence for the prevention and control of pancreatic cancer in the future. MethodsThe death surveillance data of Baoshan District from 2009 to 2021 were collected from the Shanghai chronic disease surveillance information management system. Crude mortality， standardized mortality，potential years of life lost （PYLL）， potential years of life lost rate （PYLLR） ， average years of potential life lost （AYLL） ， annual percentage change （APC） were calculated to analyze the trend of mortality and life loss of pancreatic cancer. ResultsFrom 2009 to 2021， a total of 2117 deaths of pancreatic cancer were reported in Baoshan District， accounting for 7.05% of all cancer deaths. The average age of the death cases was （71.18±10.97）years. The youngest was 3 years old and the oldest was 96 years old. The death component ratio of pancreatic cancer increased with time （P<0.05）， and the average death age of women was higher than that of men （P<0.05）. The crude mortality of pancreatic cancer was 17.38/10⁵ in Baoshan District from 2009 to 2021， showing a rising tendency （P<0.05） with APC of 3.74%. The standardized mortality of pancreatic cancer was 7.84/10⁵. The crude mortality of pancreatic cancer was 19.71/10⁵ in men and 14.89/10⁵ in women， both showed a tendency towards a rise （P<0.05 ） with APC of 4.44% and 2. 89%， respectively. The crude mortality of pancreatic cancer showed a tendency towards a decline in residents at ages of 45 to 60 years （ P<0.05 ）， with APC of 4.74%. The PYLL and PYLLR of pancreatic cancer were 8 115 person-years and 0.67‰ in Baoshan District from 2009 to 2021， while the AYLL of pancreatic cancer was 3.83 years per person. The PYLL was higher in men than in women. ConclusionThe mortality rate of pancreatic cancer in Baoshan District shows an increasing trend. The healthy life of elderly and men is affected largely by pancreatic cancer. It is necessary to strengthen the health education on the prevention/control of pancreatic cancer and healthy life style， thereby improving the tertiary prevention system of pancreatic cancer.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10^-15 g/L, and the quantitative limit reached 1.0 × 10^-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (K_D) of 5.701 × 10^-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a K_D of up to 4.181 × 10^-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

ObjectiveTo investigate the epidemiological characteristics of respiratory disease mortality in Baoshan residents during the period of 2009‒2020. MethodsRespiratory disease deaths of Baoshan residents from 2009‒2020 were collected. ICD-10 codes were used to classify the causes of death， and R-4.2.1 was applied for statistical analysis. The average annual percent change （AAPC） of standardized mortality rates of different respiratory diseases were analyzed by using Joinpoint 4.9.0.0. ResultsThe average annual mortality rate of respiratory diseases in Baoshan from 2009 to 2020 was 58.86/10⁵， and the standardized mortality rate was 35.62/10⁵， which was the 3rd leading cause of mortality. The mortality rate of respiratory diseases was higher in men than in women （χ²=46.70， P<0.001）. COPD ranked first among respiratory diseases in Baoshan from 2009 to 2020， followed by pneumonia， asthma and pneumoconiosis in that order. The standardized mortality rate for COPD decreased from 38.66/10⁵ in 2009 to 19.88/10⁵ in 2020 （AAPC=-6.6%， 95%CI： -8.2% to -4.9%， P<0.001）. The standardized mortality rate of asthma decreased from 2.86/10⁵ in 2009 to 1.43/10⁵ in 2020 （AAPC=-5.8%， 95%CI： -8.8% to -2.8%， P<0.01）. The standardized mortality rate of pneumoconiosis decreased from 0.64/10⁵ in 2009 to 0.12/10⁵ in 2020 （AAPC=-7.4%， 95%CI： -13.0% to -1.5%， P<0.05）. The standardized mortality rate for pneumonia decreased from 2.63/10⁵ in 2009 to 0.70/10⁵ in 2020 （AAPC=-6.2%， 95%CI： -12.2% to 0.2%， P=0.056）， but not statistically significant. The annual average mortality rates of COPD， pneumonia and asthma were all highest in January. Crude mortality rates for COPD （χ²=2 669.01， P<0.001）， pneumonia （χ²=217.82， P<0.001）， asthma （χ²=100.09， P<0.001）， pneumoconiosis （χ²=26.46， P<0.001） and all categories of respiratory diseases （χ²=2 995.84， P<0.001） increased with age showed an increasing trend. The crude mortality rates for COPD （χ²=101.69， P<0.001）， pneumonia （χ²=7.39， P<0.01） and asthma （χ²=7.41， P<0.01） were higher in the central than in the northern part of Baoshan District， while the crude mortality rate for COPD （χ²=19.97， P<0.001） was higher in the central than in the southern part. ConclusionThe attention should be focused on COPD； increased detection in males and the elderly， especially in winter and spring； and a good balance between environmental and economic when planning the regional development.

This paper summarized professor XU Jingshi's understanding and clinical experience of using Zhuru （Caulis Bambusae in Taenia）. It is suggested that suitable processed products should be flexibly selected according to the pathogenesis. Ginger-fried Zhuru is good at clearing the gallbladder and harmonizing the stomach， and balancing the ascending and descending， and self-made Xiaohua Funing Decoction （消化复宁汤）， modified Huanglian Wendan Decoction （黄连温胆汤）， and Danqi Heluo Beverage （丹七和络饮） can be used to treat palpitations， restlessness， upset， insomnia， and others. Dried Zhuru can resolve phlegm and clear heat， harmonize the center and calm spirit， and self-made Qingdan Cuimian Formula （清胆催眠方） is often used to treat palpitations， restlessness， insomnia， etc. Raw Zhuru is good at clearing the lung and dispelling phlegm， relieving cough and calming panting， which is commonly used in treating phlegm-heat cough and asthma caused by phlegm heat accumulating in the lung and ascending counterflow of lung qi. In addition， as Zhuru can clear heart and remove vexation， direct counterflow downward and relieve constraint， self-made Shugan Liyu Formula （疏肝理郁方） is often used to treat all diseases caused by constraints. Considering Zhuru has the function of harmonizing the actions of all medicinals in a formula， guiding the medicinals into the stomach， and regulating the ascending and descending of qi movement in central spleen and stomach， self-made Fuzheng Anzhong Decoction （扶正安中汤） can be used for postoperative treatment of various malignant tumors.

Objective:To analyze the efficacy and safety of cranial approach priority, counterclockwise sequential comple mesocolic excision in laparoscopic right hemicolectomy.Methods:From Jan. 2020 to Dec. 2020, 30 patients with right colon cancer in Department of Gastrointestinal Surgery were retrospectively analyzed. Laparoscopic radical right hemicolectomy was performed via the approach of complete mesocolic excision. The general clinicopathological data of the patients, perioperative data such as operation time, intraoperative blood loss, number of cases of hemorrhage caused by Henle trunk and subordinate branch injury, whether or not converted to open surgery, postoperative pathological data (TNM staging, total number of dissected lymph nodes and the number of metastatic lymph nodes) , postoperative recovery (exhaust time, the time of fluid intake, drainage tube removal and hospital stay) , and complications (such as bleeding, anastomotic leakage, secondary surgery, lymphatic leakage, pulmonary infection, abdominal infection, incision infection, etc) were recorded. Follow-up was performed by telephone or outpatient in 1 year after surgery.Results:The total operation time was (197.80±31.20) minutes, ranging from 150 to 275 minutes, and the intraoperative blood loss was (58.33±30.30) ml, ranging from 10 to 100 ml. There were no cases of intraoperative Henle stem and branch injury bleeding or conversion to open surgery. Postoperative exhaust time was (2.97±0.67) d, ranging from 2 to 4d; postoperative fluid intake time was (3.67±0.76) d, ranging from 3 to 5d; postoperative drainage tube removal time was (6.60±4.00) d, ranging from 4 to 25 days; postoperative hospital stay was (7.87±3.94) days, ranging from 5 to 26 days. pTNM staging: 9 cases of stage I, 5 cases of stage IIA, 1 case of stage IIB, 6 cases of stage IIIA, 4 cases of stage IIIB, and 5 cases of stage IIIC. The total number of lymph nodes dissected was (29.50±8.18) , ranging from 19 to 51; the number of metastatic lymph nodes was (1.40±1.77) , ranging from 0 to 6. Postoperative complications included incision infection in 1 case, anastomotic leakage in 1 case, lymphatic leakage in 2 cases, and lung infection in 1 case. No tumor recurrence or metastasis was found during follow-up, and no patient died.Conclusion:Cranial approach priority, counterclockwise sequential complete mesocolic excision is safe and effective in laparoscopic right hemicolectomy.

Objective:To analyze the relationship between perineural invasion and other clinicopathological factors and its effect on the prognosis of gastric cancer.Methods:The clinicopathological data of 665 patients with gastric cancer were retrospectively analyzed. According to the presence of perineural invasion, the patients were divided into perineural invasion positive group and perineural invasion negative group. The relationship between perineural invasion and other clinicopathological factors and its effect on the prognosis of gastric cancer were analyzed. After eliminating the potential confusion bias between the two groups by propensity score matching (PSM) , the differences of 5-year cumulative survival rate between the two groups of gastric cancer patients were compared.Results:The incidence of perineural invasion was 17.0% (113 cases) . The binary logistic regression analysis showed that the depth of tumor invasion and vascular tumor thrombus were independent factors influencing the occurrence of gastric cancer perineural invasion (all P<0.001) . Univariate analysis showed that age (>60 years) , tumor diameter (>4 cm) , borrmann classification, depth of invasion, lymph node metastasis, TNM stage, degree of differentiation, vascular tumor thrombus, perineural invasion, tumor nodule, tumor site, resection site, and surgical operation were the influencing factors for the prognosis of patients with gastric cancer ( P<0.05) , but multivariate analysis showed that age (>60 years) , tumor diameter (>4cm) , depth of invasion, lymph node metastasis, and positive vascular tumor thrombi were independent risk factors affecting the prognosis of gastric cancer patients ( P<0.05) .However, perineural invasion cannot be an independent factor influencing the poor prognosis of gastric cancer in a multivariate analysis. Survival analysis was performed after propensity matching scores, and it was found that there was no statistically significant difference in the five-year survival rate between the perineural invasion positive group and the perineural invasion negative group (34.6% vs 43.0%; χ2=1.713; P=0.191) ,and there was no significant difference in the survival curve analysis between the two. Conclusion:Most patients with gastric cancer of perineural invasion have poor prognosis, but perineural invasion cannot be an independent prognostic factor for the prognosis of gastric cancer.

How to effectively repair esophageal fistulas, caused by esophageal perforation, rupture and anastomotic leakage after esophagectomy has always been a key problem for the digestive surgeon. Although there are many clinical treatment methods, the therapeutic effect is still completely unsatisfactory, especially when severe mediastinal purulent cavity infection is associated with the esophageal fistula. In recent years, foreign centers have promoted a new minimally invasive endoscopic treatment technology to repair the esophageal fistula, endoscopic vacuum-assisted closure therapy, with significantly curative effect. In this article, we will review the specific operation, advantages and disadvantages, as well as the clinical efficacy of endoscopic vacuum-assisted closure therapy in treating the esophageal fistulas, to provide a new therapeutic technique for esophageal fistulas and expand the new field of minimally invasive endoscopic therapy.

Objective:To study the effect of enhanced recovery after surgery (ERAS) on intestinal function and gut microbiota changes in patients who underwent laparoscopic gastrectomy.Methods:From Aug. 2018 to Dec. 2019, 80 patients who underwent laparoscopic radical D2 gastrectomy for gastric cancer in the first Department of Gastrointestinal Surgery of Yantai Yuhuangding Hospital were selected. According to whether it adopts ERAS treatment or not, patients were divided into 2 groups (n=40) : ERAS group and traditional perioperative treatment group. The time of postoperative bowel sounds, the time of first exhaust and defecation, the proportion of antibiotic-related diarrhea and surgical site infection (SSI) were recorded. Stools were collected before operation, first time after operation, 1, 2 weeks and 1 month after operation. 16S rRNA sequencing method was used to identify the diversity and species of gut microbiota. The diversity index of intestinal flora in the perioperative period and changes in the proportion of probiotics (bifidobacterium and lactobacillus) were compared.Results:The appearance time of bowel sounds, the first exhaust and defecation time [ (16.25±6.41) h, (23.95±6.02) h, (34.95±9.34) h] in ERAS group were significantly earlier than those in the traditional treatment group [ (22.3±6.49) h, (28.45±7.12) h, (48.1±15.64) h], and the difference was statistically significant ( P<0.05) . The incidence of antibiotic-related diarrhea was higher in the traditional treatment group (3/40) than in ERAS group (1/40) , but the difference was not statistically significant ( P>0.05) . The ratio of postoperative SSI was slightly higher in ERAS group, but the difference was not statistically significant ( P>0.05) . In the perioperative period, the intestinal flora diversity index (Chao1 and Shannon index) and the proportion of probiotics (lactobacillus acidophilus and bifidobacterium) were not significantly different between the two groups before surgery ( P>0.05) ; while at the first time, one week, 2 weeks after the operation, and 1 month after the operation, ERAS group was higher than the traditional group ( P<0.05) ; and at each postoperative time point, the traditional group decreased significantly than the ERAS group. The first time decrease was the largest, ( P<0.05) ; With the passage of time after operation, the diversity of intestinal flora and the proportion of probiotics gradually recovered. By 1 month after operation, the two groups did not return to the preoperative gut microbiota diversity state or proportion. Conclusion:The concept of enhanced recovery after surgery (ERAS) promotes the recovery of intestinal function in patients with gastric cancer, does not reduce the proportion of antibiotic-associated diarrhea (AAD) or surgical site infections (SSI) , and maintains the diversity of gut microbiota balance and stability.