Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Objective:To evaluate association of peripheral blood brain-derived neurotrophic factor (BDNF) with Alzheimer's disease (AD) .Methods:Databases including Pubmed, Cochrane library, Web of science, Embase, China National Knowledge Infrastructure, CBM disc, VIP-CSTJ and Wanfang Data were used to collect case-control studies related to the concentration of BDNF in peripheral blood of dementia patients with Alzheimer's type(DAT) and mild cognitive impairment(MCI). After extracting data and appraising the quality of the included studies, meta-analysis were conducted using Review Manager 5.3 and CMA 3.0.Results:A total of 51 articles were included in the analysis, with a total subjects of 7 182, including 2 673 subjects in DAT group, 1 506 subjects in MCI group, and 3 003 subjects in control group.The Meta-analysis showed that the levels of peripheral blood BDNF in patients with DAT were significantly lower than normal control group(SMD=-0.71, 95% CI : -0.99--0.43, P<0.001) ( n=5 111), and there were no statistical differences in peripheral blood BDNF levels between MCI group and control group and between DAT group and MCI group.The subgroup analysis showed that the level of serum BDNF in patients with DAT (SMD=-0.85, 95% CI: -1.15--0.55, P<0.001)( n=4 425) and MCI(SMD=-0.38, 95% CI: -0.62--0.14, P=0.002)( n=2 476) was significantly lower than that in normal control group, and the level of serum BDNF (SMD=-0.76, 95% CI: -1.37--0.16), P=0.01)( n=1 630) in patients with DAT was lower than that in MCI; However, there were no statistical difference among DAT, MCI and control groups in the level of plasma BDNF( P>0.05). Conclusion:The patients with DAT and mild cognitive impairment have lower level of serum BDNF, which suggesting that serum BDNF level may be a potential biomarker for early diagnosis of AD.

Objective:To assess the prevalence of metabolic syndrome(MS) and its relationship with hyperuricemia(HUA) in perimenopausal women in Anning city, Yunnan province.Methods:This is a cross-sectional survey. In May 2021, a multi-stage stratified sampling method was used to collect demographics and clinical data [ethnicity, living community, height, weight, waist circumference, blood pressure, fasting plasma glucose, triglycerides(TG), serum uric acid, high density lipoprotein-cholesterol(HDL-C), alanine transaminase(ALT), etc] in a total of 6 721 perimenopausal women aged 45-60 years.Results:A total of 6 721 perimenopausal women were included in this study. The prevalences of MS and HUA were 14.05%(95% CI 13.22%-14.88%) and 6.46%(95% CI 5.88%-7.07%), respectively. The average age, HDL-C, urea, direct bilirubin, and albumin levels in the perimenstrual HUA population were lower than those in the non-HUA population while the levels of TG, ALT, heart rate, body mass index(BMI), and creatinine were higher(all P<0.05). The prevalence of HUA in perimenopausal women with ethnic minorities and family history of chronic diseases was higher than that in Han nationality and without family history of chronic diseases. The prevalence of MS in perimenopausal women was increased with the increase of serum uric acid( Z=-15.313 8, P<0.001). Multivariate logistic regression model showed that HUA was positively correlated with MS( OR=1.526, 95% CI 1.192-1.954) after adjusting for covariates such as BMI and ethnicity, and the incidence of MS in perimenopausal women in HUA group was 1.526 folds higher than that in non-hyperuricemia group. Conclusion:HUA is highly positively correlated with MS in perimenopausal women. The management of uric acid level in perimenopausal women should be strengthened.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Objective:To construct a plasmid for expression Mycobacterium tuberculosis ( Mtb) Rv3133c and to evaluate the immunogenicity of Rv3133c through population and mice experiments. Methods:The recombinant expression plasmid pPROEX-Rv3133c was constructed. The transformed E. coli BL21 (DE3) carrying expression plasmid was induced by IPTG to express the recombinant Rv3133c (rRv3133c). Western blot was used to identify the expressed protein. Whole-blood IFN-γ release assay (WBIA) was preformed to assess the immunogenicity of rRv3133c in Mtb-infected population. Antigen-specific antibodies in serum, Th1 type cytokines in splenocytes, functional T cell subset responses in splenocytes and the expression of cytokines at mRNA level in lung tissues were detected after immunizing mice subcutaneously with rRv3133c and adjuvant DC. Results:The rRv3133c was constructed and expressed successfully. Stimulation with rRv3133c promoted the production of IFN-γ in Mtb-infected population, especially in patients with latent tuberculosis infections. After immunizing mice with rRv3133c+ DC, the levels of IFN-γ, TNF-α and IL-2, the number of IFN-γ + TNF-α + CD4 + T cells in spleen and the expression of antigen-specific IFN-γ, TNF-α and iNOS at mRNA level in lung tissues were higher than those in BCG-immunized mice, but lower than those in BCG+ rRv3133c+ DC group. The serum IgG2a/IgG1 ratios in the rRv3133c+ DC group and the BCG+ rRv3133c+ DC group were greater than 1, and significantly higher than that of the BCG group. Conclusions:The rRv3133c had good immunogenicity and could induce strong Th1 immune response, suggesting that it was a potential candidate antigen for subunit vaccine against tuberculosis.

Objective: To observe the effects of electroacupuncture (EA) pretreatment on motor function, cerebral blood flow, cerebral infarction volume, and vascular endothelial growth factor (VEGF) level in middle cerebral artery occlusion (MCAO) model rats. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into a normal group, a model group, and an EA group, with eight rats in each group. The middle cerebral artery ischemia-reperfusion model was established by the suture-occluded method in the model group and the EA group, while not in the normal group. The EA group was pretreated with EA at bilateral Fengchi (GB20) before model preparation, once a day for 30 min each time for a total of 7 d. The changes in the CatWalk gait parameters, modified Bederson neurological deficit score, cerebral blood flow, cerebral infarction volume after ischemia, and VEGF level in the brain tissue of rats in each group were observed. Results: Compared with the normal group, the modified Bederson neurological deficit score in the model group and the EA group increased after modeling (P<0.05), and the CatWalk gait parameters (one-leg stance duration, gait cadence, and gait cycle) were all changed (P<0.05). Compared with the model group, the modified Bederson neurological deficit score in the EA group decreased (P<0.05), and the CatWalk gait parameters improved (P<0.05). Immediately after ischemia, the cerebral blood flow in the normal group was greater than that in the model group and the EA group (P<0.05); after reperfusion, the cerebral blood flow in the EA group was greater than that in the model group (P<0.05). Compared with the normal group, the cerebral infarction volume in the model group and the EA group increased (P<0.05). Compared with the model group, the cerebral infarction volume in the EA group decreased (P<0.05). The expression level of VEGF-positive cells in the rat brain tissue in the model group was higher than that in the normal group (P<0.05), and was higher in the EA group than in the model group (P<0.05). Conclusion: EA pretreatment improves the limb motor function in MCAO model rats, alleviates the symptoms of neurological deficits, promotes the recovery of cerebral blood flow, reduces the cerebral infarction area after MCAO modeling, and increases the VEGF expression in the brain tissue.

Objective:To explore the metabolic outcomes of type 2 diabetes patients with different durations after 1 year treatment under the standardized metabolic disease management model.Methods:(1)From September 2017 to September 2018, 345 type 2 diabetes patients in the Standardized Metabolic Management Center(MMC) of Shanghai General Hospital were recruited and included in this research. They were divided into newly-diagnosed type 2 diabetes(duration≤1 year) and long-term groups(duration>1 year). The general characteristics, blood pressures, glycemic levels, lipids levels, control rates and comprehensive compliance rates(blood glucose, pressure and lipids all reached targets) were compared at baseline between 2 groups.(2)All patients underwent one year standardized management, and metabolic indicators mentioned above and control rates at the time were compared as well.Results:(1) At baseline, compared with long-term group, patients in newly-diagnosed type 2 diabetes group were younger ( P<0.01), and 2 h blood glucose level after glucose loading were higher [(15.20±5.26 vs 13.68±4.94) mmol/L, P<0.01]. (2) After one year standardized management, body weight, blood pressure, glucose and lipids metabolism in all patients were significantly improved. Compared with patients in long-term group, newly-diagnosed type 2 diabetes patients achieved better glycemic level [fasting blood glucose(6.27±1.56 vs 7.63±2.08) mmol/L, P<0.01; glycated hemoglobin(6.33±0.96 vs 7.23±1.37) %, P<0.01] , and had higher HOMA-β [(74.01±56.45 vs 40.17±37.07) %, P<0.01]. The glycemic control, blood pressure and blood lipids control rates in both groups increased significantly in one year. Comprehensive compliance rate of the whole patients increased from 5.80% to 24.06%. The metabolism indexes of the newly-diagnosed type 2 diabetes group were better than those of the long-term group[comprehensive compliance rate: (24.73% vs 17.18%, P=0.087, glycemic control rate(84.62% vs 53.37%, P<0.01)]. Conclusion:Standardized metabolic disease management promoted the overall improvement in blood glucose, blood pressure, and lipids levels in type 2 diabetes patients, especially in terms of blood glucose and those of the newly-diagnosed type 2 diabetes. In the future, we should focus on the early diagnosis and treatment of type 2 diabetes, actively promote the MMC model and stress the integrated management of blood glucose, blood pressure, and blood lipid levels. We should pay more attention to the long-term patients, to improve their awareness and treatment compliance.

Objective:To explore the role of interleukin (IL)-9 and other T helper (Th) cell-related cytokines in the pathogenesis of acute anterior uveitis.Methods:A cross-sectional study was conducted.Thirty-six patients (36 eyes) with acute anterior uveitis who were treated at Gansu Provincial Hospital from May 2018 to May 2019 and 40 matched healthy subjects (40 eyes) who had no eye diseases or systemic diseases in the same period were enrolled as the acute anterior uveitis group and healthy control group, respectively.The disease severity of the subjects in the acute anterior uveitis group was graded and the subjects were divided into mild, moderate and severe groups according to the grading.Serum of all subjects was collected to determine the concentration of serum IL-9, IL-17, transforming growth factor-β 1 (TGF-β 1), interferon-γ (IFN-γ), IL-4, IL-35 and IL-22 by enzyme linked immunosorbent assay (ELISA) method.Spearman rank correlation analysis was used to evaluate the relationship between IL-9 concentration and other Th cell-related cytokines.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Gansu Provincial Hospital (No.2019-204). Written informed consent was obtained from each subject prior to any medical examination. Results:The serum levels of IL-9, IFN-γ, IL-4, TGF-β 1, IL-35 and IL-22 in the acute anterior uveitis group were significantly higher than those in the healthy control group, and the differences were statistically significant (all at P<0.05). There was no statistically significant difference in the concentration of IL-17 between the two groups ( U=704.500, P=0.872). The IL-9 concentration of patients with acute anterior uveitis in the mild, moderate and severe groups was 57.24 (47.47, 65.10), 71.68 (67.55, 78.91) and 114.01 (74.78, 139.30) ng/L, respectively, and the overall difference was statistically significant ( Z=8.766, P=0.012), and the IL-9 concentration of the mild group and the moderate group was significantly lower than that of the severe group (both at P<0.05). The concentration of IL-9 in the patients with acute anterior uveitis was positively correlated with the concentration of IL-17, TGF-β 1 and IL-35 ( rs=0.449, 0.517, 0.400; all at P<0.05), and no significant correlations were found between the concentration of IL-9 and the concentration of IFN-γ, IL-4 and IL-22 ( rs=0.293, 0.286, 0.316; all at P>0.05). Conclusions:IL-9 plays a role in promoting the immune inflammatory response in the occurrence and development of acute anterior uveitis, and it is closely related to Th17 and Treg cell-related cytokines (TGF-β 1, IL-35).

Objective:To evaluate the relationship between preoperative frailty and postoperative cognitive dysfunction (POCD) in elderly patients undergoing non-cardiac surgery.Methods:A total of 336 elderly patients of both sexes, aged≥65 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with body mass index of 18.6-25.1 kg/m 2, undergoing elective non-cardiac surgery under general anesthesia, were enrolled in the study.Faltering status was assessed with the Clinical Faltering Scale at 1 day before surgery.Mini-Mental State Examination score, Digital Span Test, Digit Symbol Substitution Test, Stroop Color and Word Test, Visual Word Learning Test and Trail Making Test were performed at 1 day before surgery and at 1, 7 and 30 days after surgery.The Z score was used to identify POCD.The patients was divided into non-POCD group and POCD group according to the occurrence of POCD within 30 days after surgery.Logistic regression analysis was used to identify the risk factors for POCD in elderly patients undergoing non-cardiac surgery. Results:The results of logistic regression analysis showed that preoperative frailty and diabetes mellitus were independent risk factors for POCD in elderly patients undergoing non-cardiac surgery ( P<0.05). Conclusion:Preoperative frailty is an independent risk factor for POCD in elderly patients undergoing non-cardiac surgery.

From September to November 2019, three patients with Hornet stings were admitted to hospital with acute anaphylaxis and various degrees of organ dysfunction. After hemoperfusion combined with continuous hemodialysis and hormone pulse therapy, 1 patient was successfully treated and 2 patients were not cured. Bee Stings can cause systemic allergic reactions and toxic reactions. In severe cases, acute anaphylaxis, rhabdomyolysis, intravascular hemolysis, abnormal coagulation, and acute liver and kidney injury may occur, myocardial damage and other multi-organ function damage or even failure, is a clinical acute and critical illness, mortality is higher. Through the analysis of the diagnosis and treatment process of these 3 cases, the experience is summarized: the Bee sting should be treated as soon as possible, the early prevention and treatment of multiple organ dysfunction, the choice of accurate blood purification and comprehensive treatment, can effectively improve the prognosis, increase the success rate of treatment.