Objective: To investigate the effects of Zuogui Jiangtang Yishen Formula (左归降糖益肾方, ZGJTYSF) in regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) signaling axis on pyroptosis in rats with diabetic kidney disease (DKD). Methods: Fifty male specific pathogen-free (SPF) grade Goto-Kakizaki (GK) rats (12 weeks old) were fed a high-fat diet for one month to establish an early DKD model. Model establishment was confirmed when fasting blood glucose (FBG) ≥ 11.1 mmol/L and urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. The successfully modeled early DKD rats were randomly divided by random number table into five groups (n = 10 per group): model group; dapagliflozin group (1.0 mg/kg, by gavage, served as positive control); and low-, medium-, and high-dose of ZGJTYSF groups (4.9, 9.9, and 19.9 g/kg, respectively, by gavage). Age-matched male SPF Wistar rats (n = 10) served as control group. Rats in control and model groups were gavaged with equivalent volumes of distilled water. Treatment lasted 12 weeks. Changes in uACR, FBG, and renal function were observed in all groups. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining were used to observe renal histopathological changes. Immunohistochemistry was performed to detect the localization and expression of caspase-1, GSDMD, and NLRP3 in rat renal tissues. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was utilized to detect pyroptosis in renal tissues. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were applied to detect mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, interleukin (IL)-1β, and IL-18. Results: Compared with model group, all doses of ZGJTYSF showed reductions in FBG, with medium- and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12 (P < 0.05). For uACR, all doses of ZGJTYSF groups exhibited a decreasing trend, with high-dose of ZGJTYSF group being significantly lower than low- and medium-dose of ZGJTYSF groups at week 12 (P < 0.05) and showing no significant difference from dapagliflozin group (P > 0.05). No significant differences in renal function parameters (serum creatinine, blood urea nitrogen, and uric acid) were observed among groups (P > 0.05). Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group, with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group. Immunohistochemistry demonstrated significantly reduced expression of caspase-1, GSDMD, and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group (P < 0.05 or P < 0.01), while the differences in low- and medium-dose of ZGJTYSF groups were not statistically significant (P > 0.05). TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups (P < 0.01), indicating a marked reduction in pyroptotic cells. Molecular analysis revealed that compared with model group, both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 in renal tissues (P < 0.01), while low- and medium-dose of ZGJTYSF groups showed downward trends without statistical significance (P > 0.05). Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis, thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.

ObjectiveTo explore the protective effects and potential mechanism of Zuogui Jiangtang Yishen prescription （ZJYP） in Goto-Kakizaki （GK） rats with early-stage diabetic kidney disease （DKD）. MethodFifty 12-week-old male GK rats were included in this study. DKD was induced after one month of high-fat feeding， with fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1 and urinary albumin/creatinine ratio （ACR） ≥ 30 mg·g^-1 used as model criteria. After successful modeling， DKD rats were randomly divided into five groups （n=10 in each group）： the model group， the western medicine group treated with dapagliflozin （1.0 mg·kg^-1·d^-1）， low-， medium-， and high-dose ZJYP groups （4.9， 9.9， 19.9 g·kg^-1·d^-1 by gavage）. Ten Wistar rats served as normal controls， with both the normal and model groups receiving physiological saline in the same volume as the treatment groups by gavage for 8 weeks. The urinary ACR， FBG， body weight， and liver and kidney functions of the rats were observed. Renal tissues were subjected to haematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining and examined under an electron microscope to observe pathological changes. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect miRNA-27a， Wnt， and β-catenin mRNA and protein expression levels in renal tissues. ResultCompared with the results in the normal group， the FBG levels in DKD rats of the model group increased significantly at 0， 2， 4， 6， and 8 weeks of drug intervention （P<0.05）， and urinary ACR increased significantly at 0， 4， 8 weeks （P<0.05）. Renal pathological staining and electron microscopy revealed an increase in mesangial cells and matrix， slight thickening of the basement membrane， and increased interstitial fibrosis and renal tubular atrophy in the model group. The mRNA expression levels of miRNA-27a， Wnt， and β-catenin were significantly higher in the model group than in the normal group （P<0.05）. Renal Wnt and β-catenin protein levels were also significantly higher in the model group （P<0.05）. After drug intervention， the FBG levels in the low-， medium-， and high-dose ZJYP groups showed a dose-dependent decrease compared with those in the model group at 6 and 8 weeks （P<0.05）. The urinary ACR also showed a dose-dependent decrease in the low-， medium-， and high-dose ZJYP groups， but the differences were not statistically significant. There were no significant differences in liver function， renal function， renal index， or routine blood lipid test results among the low-， medium-， and high-dose ZJYP groups. Renal glomerular and tubular lesions were milder in the ZJYP groups and the western medicine group than in the model group， with similar pathological changes observed in the high-dose ZJYP group and the western medicine group. The renal mRNA levels of miRNA-27a， Wnt， and β-catenin were significantly lower in the high-dose ZJYP group （P<0.05）， and renal Wnt and β-catenin protein levels were significantly lower in both the western medicine group and the high-dose ZJYP group compared with the levels in the model group （P<0.05）. The Wnt and β-catenin protein levels were lower in the renal tissues of the low- and medium-dose ZJYP groups compared with the levels in the model group， but the differences were not statistically significant. ConclusionZJYP can effectively improve glucose metabolism and alleviate early damage in DKD rats， thereby delaying the progression of DKD. Its mechanism may be related to the inhibition of the miRNA-27a/Wnt/β-catenin signaling pathway in renal tissues.

Objective:To construct a leadership evaluation indicator system for managers in primary healthcare institutions.Methods:This study was a qualitative research. Based on the Chinese Academy of Sciences′ Five Forces Model of Leadership, the framework of the leadership evaluation indicator system for primary healthcare institution managers was initially constructed through literature review, expert interviews, surveys, and group discussions. From November 2020 to June 2021, 19 experts were invited to participate in two rounds of Delphi expert consultations. Based on the consultation results, the leadership evaluation indicator system for primary healthcare institution managers was developed, and the analytic hierarchy process (AHP) was used to determine the weight of each indicator.Results:Nineteen consulting experts were included in the study, 13 of whom were aged 40 years or older, and seven of whom had 20 years or more of professional experience. The response rates of the two rounds of Delphi expert consultation questionnaires were 18/19 and 19/19, respectively; the authority coefficients of the experts were 0.92 and 0.91, respectively. In the second round of consultation, the coordination coefficients of each level of indicators were 0.640, 0.557, and 0.512 ( P<0.05), respectively. The constructed leadership indicator system for managers of primary healthcare institutions included five primary indicators, 16 secondary indicators, and 44 tertiary indicators. The primary indicators, in order of their weight, were "influence"(0.299),"decisiveness"(0.245),"control"(0.156),"inspiration"(0.150), and "foresight"(0.150). Conclusions:This study is a preliminary construction of a leadership evaluation indicator system for managers of primary healthcare institutions, which can be a reference for the training and evaluation of relevant talents.

Objective:To investigate the current status of research on the construction of leadership indicator system in the medical field at home and abroad, and to analyze the characteristics of the indicator system therein.Methods:This was a bibliometric study. The group applied subject keywords to search relevant literature on the construction of leadership indicator system in the medical field at home and abroad on English websites PubMed, Web of Science, Google Scholar, CINAHL, Scopus and Chinese websites Baidu Academic, CNKI, CQVIP, Wanfang Data Knowledge Service Platform, with a time frame of 2016-2023. The basic characteristics of the literature, the theoretical framework of the research application and the research theme were extracted, and the content of the indicator system in the literature was reviewed and summarized.Results:A total of 21 literatures were included, including 7 Chinese literatures and 14 English literatures. Of these literatures, 10 focused on physician leadership, 5 on medical manager leadership, and 2 on general practitioner leadership. Among 16 research literatures, 9 informed the theoretical basis of leadership, and 4 literatures were applied research. Five main themes were identified: leadership studies of individual healthcare administrators, leadership development in healthcare, interest and attitudes of healthcare workers towards leadership learning, applications of leadership in healthcare, and the impact of leadership in healthcare on patients and healthcare organizations.Conclusions:At present, research on the construction of the leadership indicator system in the medical field presents is diverse, with differences in theoretical basis and content. The original and empirical research is still insufficient.

Objective:To investigate effects of short-term cigarette smoke exposure combined with poly(I:C)stimulation on lung immune response and interferon expression in mice.Methods:BALB/c mice were randomly divided into 4 groups:control group,smoke group,poly(I:C)group and smoke combined poly(I:C)group.Total cell number and cell classification count of bronchoalveo-lar lavage fluid(BALF)were detected,and cell morphology was observed under ordinary light.Cytokines,chemokines,interferon and interferon stimulating genes expressions in lung tissues were detected by fluorescence quantitative PCR.Results:Compared with control group,total cell count,macrophage count and neutrophil count in smoke combined poly(I:C)group were significantly increased(P<0.05),and macrophage count was higher than that in poly(I:C)group.Macrophages of airway lavage fluid of mice in smoke combined with poly(I:C)group were larger in size,round or irregular in shape,and had more vacuoles in cytoplasm.Com-pared with control group,mRNA expressions of neutrophil chemokine CXCL1(P<0.05),CXCL2(P<0.01)and lymphocyte chemo-kine CCL2(P<0.01)in lung tissues of mice in smoke combined with poly(I:C)group were increased.IL-1β,IL-6,TNF-α mRNA expressions were significantly increased(P<0.01),IFN-β(P<0.01),IFN-γ(P<0.05),MX2(P<0.01)and IP-10(P<0.01)expre-ssions in lung tissues were significantly increased,and compared with poly(I:C)group,mRNA expressions of CXCL2(P<0.05),TNF-α(P<0.01)and IFN-β(P<0.05)in lung tissues of mice in smoke combined with poly(I:C)group were significantly increased.Conclusion:Cigarette smoke combined with poly(I:C)induces lung inflammation and expressions of interferon and interferon stimu-lating genes in mice.Cigarette exposure also increases poly(I:C)-induced acute lung inflammation and type Ⅰ interferon expression in mice.

Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

BACKGROUND: The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection. METHODS: 1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC. RESULTS: Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]). CONCLUSIONS: IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery. TRIAL REGISTRATION chictr.org.cn, ChiCTR 2100043775.
Humans ; Fluorouracil/therapeutic use* ; Leucovorin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Proportional Hazards Models ; Prognosis

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.