OBJECTIVE To explore the mechanism of gallic acid targeting β-arrestin2 to inhibit astrocyte inflammation.METHODS Potential targets of gallic acid were found by PharmMapper and verified by thermal shift and molecular docking experi-ments.Western blot was used to detect the expression of β-arrestin2,NF-κB signaling pathway and NLRP3 inflammasome-related proteins;qPCR was used to detect the mRNA levels of proinflammatory cytokines such as IL-1β,IL-6 and TNF-α.A subacute PD mouse model induced by MPTP was established,and the behavioral ability of mice was evaluated by open field test,rotating rod test and climbing pole test;the number of TH+and GFAP+cells in the SNc area of mice was detected by immunohistochemistry;Western blot was used to detect the expression of NF-κB signaling pathway and NLRP3 inflammasome-related proteins in the homogenate pro-tein of mouse midbrain tissue.RESULTS Molecular docking experiments and thermal shift experiments showed that gallic acid could directly bind to β-arrestin2.Gallic acid could reduce the expression of p-IKK and p-P65 proteins in astrocytes(P<0.001,P<0.000 1),reduce the mRNA levels of IL-1β,IL-6 and TNF-α(P<0.05,P<0.01),and reduce the expression of caspase-1 and IL-1β proteins(P<0.000 1),but had no effect on the expression of β-arrestin2 protein(P>0.05).Gallic acid could improve the be-havioral ability of PD model mice,increase the number of TH+neurons and GFAP+cells in PD model mice(P<0.05,P<0.001),and reduce the expression of caspase-1,IL-1β,NLRP3 and p-IKK proteins in the brain of PD model mice(P<0.05).CONCLU-SION Gallic acid inhibits the activation of NF-κB signaling pathway and NLRP3 inflammasome by binding to β-arrestin2 to reduce astrocyte inflammation,and has a neuroprotective effect on MPTP-induced PD model mice.

Objective To investigate the characteristics and patterns of electroacupuncture parameters in hypertension mechanism research using data mining technology.Methods Computerized searches were conducted in multiple databases including China National Knowledge Infrastructure(CNKI),Wanfang Academic Journal Full-text Database,VIP Chinese Sci-Tech Journal Database,China Biology Medicine disc(CBM),PubMed,and Web of Science.The search period spanned from the inception of each database to July 2024.Basic research studies on electroacupuncture treatment for hypertension were collected to establish an electroacupuncture parameter database for hypertension.Descriptive statistics and association analysis were performed on the extracted data.Results The initial search yielded 13 977 publications.After screening,112 articles were ultimately included for analysis.The analysis revealed that the top three most frequently used acupoints were Zusanli(ST36),Quchi(LI11),and Taichong(LR3).The most commonly employed stimulation parameters were:continuous wave,2 Hz frequency,1 mA or 2 mA intensity,once daily treatment,30 minutes per session,with a total treatment duration of 28 days or 14 days.Conclusion In hypertension mechanism research,electroacupuncture stimulation parameters are predominantly characterized by low-frequency and low-intensity stimulation,with a treatment duration typically of 28 days.However,these parameter characteristics are primarily applied in mechanistic studies,and their translation to clinical practice requires further investigation.

OBJECTIVE To explore the mechanism of gallic acid targeting β-arrestin2 to inhibit astrocyte inflammation.METHODS Potential targets of gallic acid were found by PharmMapper and verified by thermal shift and molecular docking experi-ments.Western blot was used to detect the expression of β-arrestin2,NF-κB signaling pathway and NLRP3 inflammasome-related proteins;qPCR was used to detect the mRNA levels of proinflammatory cytokines such as IL-1β,IL-6 and TNF-α.A subacute PD mouse model induced by MPTP was established,and the behavioral ability of mice was evaluated by open field test,rotating rod test and climbing pole test;the number of TH+and GFAP+cells in the SNc area of mice was detected by immunohistochemistry;Western blot was used to detect the expression of NF-κB signaling pathway and NLRP3 inflammasome-related proteins in the homogenate pro-tein of mouse midbrain tissue.RESULTS Molecular docking experiments and thermal shift experiments showed that gallic acid could directly bind to β-arrestin2.Gallic acid could reduce the expression of p-IKK and p-P65 proteins in astrocytes(P<0.001,P<0.000 1),reduce the mRNA levels of IL-1β,IL-6 and TNF-α(P<0.05,P<0.01),and reduce the expression of caspase-1 and IL-1β proteins(P<0.000 1),but had no effect on the expression of β-arrestin2 protein(P>0.05).Gallic acid could improve the be-havioral ability of PD model mice,increase the number of TH+neurons and GFAP+cells in PD model mice(P<0.05,P<0.001),and reduce the expression of caspase-1,IL-1β,NLRP3 and p-IKK proteins in the brain of PD model mice(P<0.05).CONCLU-SION Gallic acid inhibits the activation of NF-κB signaling pathway and NLRP3 inflammasome by binding to β-arrestin2 to reduce astrocyte inflammation,and has a neuroprotective effect on MPTP-induced PD model mice.

Objective:To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene.Methods:This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation.Results:All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days.Conclusions:The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.

Objective:To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene.Methods:This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation.Results:All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days.Conclusions:The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.

Objective:To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats.Methods:The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor β 1 (TGF-β 1) were detected by Western blotting ( n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results:At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-β 1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group ( t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group ( t=7.21, P<0.05). Conclusions:The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.

Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure to establish a portosystemic shunt between the hepatic vein and the portal vein via the jugular approach, so as to reduce portal venous pressure and control acute esophagogastric variceal bleeding (EGVB). The prognosis of EGVB has been improved significantly over the past few decades, and endoscopic variceal ligation combined with drug therapy is now recommended as the first-line treatment regimen for this disease. The latest research advances in the management of EGVB over the past decade have focused on the relatively new concept of "early" or "pre-emptive" TIPS, that is to say, early TIPS (within 72 hours after admission, ideally within 24 hours) is recommended for patients with EGVB who are at a relatively high risk of failure in standard treatment. This article briefly introduces the effect of early TIPS on controlling bleeding, mortality rate, and hepatic encephalopathy, the high-risk population for early TIPS, timing of intervention, cost effectiveness, the applications of early TIPS in a real-world setting, and recommendations for early TIPS in international guidelines and consensus statements.

Objective:To investigate the relationship between triglyceride glucose index (TyG) and body inflammation.Methods:The data were obtained from a baseline survey in population in Xi'an in natural population cohort study in northwest China established in 2018-2019. Based on TG and FPG, TyG/TyG-BMI was constructed to reflect insulin resistance (IR) in the body, and systemic immune-inflammation index (SII) reflecting inflammation in the body was constructed using neutrophil, lymphocyte, and platelet counts. A logistic regression model was used to explore the relationship between the TyG and the SII.Results:A total of 11 491 subjects were included in the analysis. After adjusting for covariates, each unit increase in the TyG increased the risk of high SII by 21% ( OR=1.21, 95% CI:1.12-1.30). The risk of high SII in the group with the TyG in Q4 was 1.34 times higher than that in the group Q1 ( OR=1.34, 95% CI:1.18-1.52). Both sensitivity analysis and subgroup analysis further confirmed the stability of the association between the TyG and the SII. In the population with a BMI ranging from 18.5 to 23.9 kg/m 2, for every unit increase in the TyG as a continuous variable, the risk for high SII increased by 31% ( OR=1.31, 95% CI:1.18-1.45). As a categorical variable, the risk for high SII in the Q4 group was 1.52 times higher than that in the Q1 group ( OR=1.52, 95% CI:1.27-1.83). In a population with BMIs ranging from 24.0 to 27.9 kg/m 2, for every unit increase in the TyG as a continuous variable, the risk for high SII increased by 20% ( OR=1.20, 95% CI:1.07-1.35), and there was no significant difference when it was a categorical variable. Conclusions:The increase in IR is closely related to the development of inflammation in the body, and BMI may regulate their relationship. Early prevention of elevated IR levels before overweight or obesity may have a positive effect on the control of inflammation in the body.

Cohort study is one of the important research methods in analytical epidemiology because of its clear time sequence relationship, which is better than other observational studies in demonstrating causal association. However, screening diagnosis or other methods are often used to exclude the individuals with outcome events during the enrollment process of the subjects in cohort studies. The accuracy of screening diagnosis and the effectiveness of exclusion will affect the accuracy of the baseline status assessment of the subjects included in the study, which may lead to the causal time sequence reversal of exposure-outcome in the estimation of causal effect. Landmark analysis can be used to control reverse causality by excluding subjects with potentially unknown expose-outcome timing. In this paper, we describe the basic principles and analytical steps of landmark analysis, and use data from the Chinese Longitudinal Healthy Longevity Survey to explore the relationship between physical activity and frailty, and introduce the specific application of landmark analysis for the purpose of facilitating its application and inferring causal effects more accurately in cohort studies.

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.