ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease （DKD） by regulating the cyclic adenosine monophosphate （cAMP） signaling pathway. MethodsThirty specific pathogen-free （SPF） male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L^-1 and urinary albumin-creatinine ratio （ACR） ≥ 30 mg·g^-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group： the model group， the low-， medium-， and high-dose Bushen Kaixuan Tongluo prescription groups （administered at doses of 7， 14， 28 g·kg^-1·d^-1 respectively）， and the positive drug irbesartan group （administered at a dose of 20 mg·kg^-1·d^-1）. Additionally， six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations， irbesartan， or an equal volume of pure water， and the intervention lasted for 12 weeks. During the experiment， the general conditions， body weight changes， and renal function indicators of the mice were dynamically monitored. After the intervention， a blood glucose meter was used to measure the fasting blood glucose （FBG） of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary microalbumin （uALB）， ACR， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， leptin （LEP）， glycosylated serum protein （GSP）， and insulin （INS） in the mice. Renal tissues were collected for hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry （IHC） was used to detect the expressions of protein kinase A （PKA） and cAMP response element-binding protein （CREB） in the mice. Western blot analysis was performed to determine the expression levels of PKA， phosphorylated protein kinase A （p-PKA）， CREB， phosphorylated cAMP response element-binding protein （p-CREB）， and B-cell lymphoma-2 （Bcl-2） proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of PKA， CREB， and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group， the mice in the model group showed listlessness， decreased activity， and a significant increase in body weight （P<0.01）. Biochemical indicators revealed that the levels of BUN， uALB， ACR， AST， ALT， TC， TG， FBG， LEP， GSP， and INS were significantly increased （P<0.01）， while SCr showed an increasing trend with no statistically significant difference. Compared with the model group， the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN， uALB， ACR， TC， GSP， and INS were significantly decreased （P<0.05）， while SCr， AST， ALT， TG， and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane， expansion of the mesangial matrix， and deposition of collagen fibers in the renal tubulointerstitium， and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group， the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased （P<0.01）. Compared with the model group， the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased （P<0.01）， while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group， the expression levels of p-PKA/PKA， p-CREB/CREB， and Bcl-2 in the model group were significantly decreased （P<0.05）. Compared with the model group， the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased （P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expressions of PKA， CREB， and Bcl-2 in the model group were significantly down-regulated （P<0.05）. Compared with the model group， the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated （P<0.05）. ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice， correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress， thereby protecting renal function.

An increasing number of studies have shown that there is a close relationship between Alzheimer's disease(AD)and diabetes mellitus(DM).Traditional Chinese medicine holds that"kidney yin deficiency"is the common pathogenesis of these two diseases,while modern medicine believes that their pathogenesis involves abnormal aggregation of amyloid proteins,insulin deficiency and resistance,inflammatory response,oxidative stress,and autophagy,among others.The well-known traditional Chinese medicine formula Liuwei Dihuang Pills plays a significant role in the treatment of these two diseases with the same therapeutic approach.Therefore,this article will explore the connection between Liuwei Dihuang Pills and the treatment of AD and DM from different aspects;analyze the common etiology and pathogenesis of AD and DM,and explain the mechanism of prevention and treatment of Liuwei Dihuang Pills,with the aim of providing new ideas and methods for the integrated traditional and Western medicine prevention and treatment of AD and DM in the future.

Epidemiology research has found that ABO blood group and the gene coding ABO glycosyltransferases are associated with many human diseases. The activity of ABO glycosyltransferases varies with different blood types, mediating different glycosylation modifications. The variation in glycosylation level might be the risk factor of specific disease. Based on the literature retrieval and analysis, glycosylation levels regulated by ABO glycosyltransferases mainly affect the ABH blood group antigens and von Willebrand factor (vWF). By modulating key glycosylation components, ABO glycosyltransferases partly determine the activity or expression levels of the ABH antigens and vWF, thereby affecting the development and progression of diseases. Exploring the pathogenic mechanisms of ABO glycosyltransferases can improve the understanding of the molecular pathology of related diseases and provide reference for clinical research and application.

Objective:To explore the association between spicy food intake and the risk for cardio/cerebrovascular diseases.Methods:Data were collected from the China Kadoorie Biobank project conducted in Pengzhou, Sichuan Province. Using the Cox proportional hazards regression model, we analyzed the associations of the frequency of spicy food intake, spicy level, types of spicy food, and the age when regular intake of spicy food began (intake in 1 day/week), with the risk for cardio/cerebrovascular disease. Furthermore, the associations with the risks for ischemic heart disease (IHD) and cerebrovascular diseases, as well as the risk of ischemic stroke (IS) and hemorrhagic stroke (HS) were analyzed.Results:A total of 54 859 study participants were included in the study, in whom 49 320 had spicy food intake (89.90%). In these participants, 37 680 (68.69%) had spicy food intake in 6-7 days/week, 5 036 (9.18%) had spicy food intake in 1-5 days/week, and 6 604 (12.03%) had spicy food intake once a week; 5 539 (10.10%) had never/almost never had spicy food intake. After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risks for IHD (intake in 6-7 days/week: HR=0.86, 95% CI: 0.78-0.95), cerebrovascular diseases (intake in 6-7 days/week: HR=0.88, 95% CI: 0.81-0.96), and IS (intak in 6-7 days/week: HR=0.85, 95% CI: 0.76-0.95). With the increase of spicy food intake frequency, the risk for cardio/cerebrovascular disease decreased (intake in 1-5 days/week: HR=0.91, 95% CI: 0.85-0.98; intake in 6-7 days/week: HR=0.89, 95% CI: 0.84-0.94) (trend test P<0.001). However, no statistical association was found between spicy food intake and the risk for HS. In terms of spicy level, after adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risk for cardio/cerebrovascular disease (moderate: HR=0.86, 95% CI: 0.82-0.90) and cerebrovascular disease (moderate: HR=0.90, 95% CI: 0.84-0.97). With the increase of spicy level, the risk for IHD decreased (moderate: HR=0.86, 95% CI: 0.79-0.93; strong: HR=0.84, 95% CI: 0.74-0.95) (trend test P<0.001). After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of any type of spicy food was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regulat intake of spicy food from age 0-10 years was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regular intake of spicy food from age 11-20 years reduced the risk for cardio/cerebrovascular disease and IHD. There was no significant association between the regular intake of spicy food from age 21-79 years and the risks for cardio/cerebrovascular disease, IHD and cerebrovascular disease. Conclusion:The intake of spicy food could reduced the risk for cardio/cerebrovascular diseases, IHD, cerebrovascular diseases and IS in residents aged 30-79 years in Sichuan.

Objective:To investigate the effect of physical activity on mortality risk in patients with chronic obstructive pulmonary disease (COPD) in Sichuan Province.Methods:Based on baseline data from 2004 to 2008 from the China Kadoorie Biobank project site in Pengzhou City, Sichuan Province, a total of 8 501 COPD patients aged 30-79 years were enrolled and followed up for a long period to determine mortality outcomes. Quartiles were used to group physical activity levels. The Cox proportional hazards regression model was used to analyze the effect of physical activity level on mortality outcomes.Results:As of December 31, 2017, the cumulative follow-up of the participants totaled 85 600.58 person-years (mean follow-up duration: 10.07 years). During this period, a total of 2 000 deaths were recorded, yielding a cumulative mortality rate of 23.53%. Among these deaths, 665 were attributed to COPD, corresponding to a cumulative mortality rate of 7.82%; and 1 116 were attributed to cardiovascular and cerebrovascular disease (CVD), corresponding to a cumulative mortality rate of 13.13%. The Cox proportional hazards regression model analysis revealed that, after adjusting for confounding factors, total physical activity was associated with a reduced risk of mortality from COPD, CVD, and all causes in patients with COPD. Compared with the low-level group of total physical activity, the medium-high-level group had the lowest risk of COPD mortality, with an HR of 0.39 (95% CI: 0.30-0.49). The high-level group had the lowest risk of CVD death and all-cause death, with HRs of 0.46 (95% CI: 0.37-0.56) and 0.55 (95% CI: 0.48-0.64), respectively. The lowest risk of COPD death and CVD death was found in the medium-high level of work-based physical activity group, with HRs of 0.36 (95% CI: 0.28-0.46) and 0.43 (95% CI: 0.36-0.51), respectively; the risk of all-cause mortality was lowest in the medium-high and high-level groups, with HRs values of 0.53 (95% CI: 0.46-0.61) and 0.53 (95% CI: 0.45-0.61). The risk of COPD death was lowest in the high-level transportation physical activity group, with an HR of 0.66 (95% CI: 0.53-0.83), and the risk of CVD and all-cause death was lowest in the medium-high level group, with HRs of 0.63 (95% CI: 0.53-0.76) and 0.73 (95% CI: 0.64-0.84), respectively. The risk of COPD death and CVD death was the lowest in the high-level domestic physical activity group, with HRs of 0.66 (95% CI: 0.49-0.89) and 0.76 (95% CI: 0.61-0.95), respectively, and the risk of all-cause death was the lowest in the medium-high level group, with an HR of 0.82 (95% CI: 0.72-0.94). There is no statistical association between leisure physical activity and the risk of death from three types of diseases. Conclusions:Total physical activity, including work-based, transportation-based, and domestic physical activity, reduced the risk of COPD, CVD, and all-cause mortality in patients with COPD in Sichuan Province. The magnitude of mortality risk was influenced by the type and level of physical activity.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective:To investigate the feasibility and clinical effect of arthroscopic limited excision of flexor hallucis longus(FHL) tendon sheath combined with open technique of posterior ankle joint capsule for hallucal ganglion cyst(HGC) deriving from the ankle joint.Methods:This is a retrospective case series study. From September 2021 to September 2023, the clinical data of 18 patients (18 feet) with HGC deriving from ankle joint treated by arthroscopic limited excision of FHL tendon sheath combined with posterior ankle capsule opening technique at Department of Orthopedic, Xuzhou Central Hospital were analyzed retrospectively. There were 12 males and 6 females. The age was (49.5±10.7) years (range:32 to 66 years). There were 10 cases on the right side and 8 cases on the left side; 11 cases in fibular, 3 cases in plantar, 2 cases in tibial and 2 cases in tip. There were 8 cases of primary operation and 12 cases of recurrence after resection in other hospital. There were 10 cases with complete skin and soft tissue and 8 cases with ulcer.All patients underwent arthroscopic limited excision of FHL tendon sheath combined with open technique of posterior ankle joint capsule.Clinical evaluations included the American Orthopedic Foot and Ankle Society ankle-hindfoot score(AOFAS-AH), visual analog scale (VAS). The data were compared by paired sample t test and Wilcoxon rank sum test. Results:All cases successfully completed the operation. The operation time was (46.3±8.1) minutes (range:35 to 65 minutes), and the intraoperative blood loss was (6.8±3.1)ml (range:2 to 15 ml). All patients primarily healing without any complications such as infection and skin necrosis. All 18 patients were followed up for (16.3±2.9) months (range:12 to 20 months),and no recurrence. One patient complained of numbness of tibial nerve innervation, and the symptoms disappeared after 3 months of symptomatic treatment with oral mecobalamin. At the last follow-up, the AOFAS-AH significantly improved from 78.9±7.1 (range:65 to 90) preoperatively to 95.8±3.3 (range:89 to 100) postoperatively ( t=9.62, P<0.01). The VAS ( M(IQR)) was reduced from 3(4) preoperatively to 0(1) postoperatively ( Z=-3.75, P<0.01). Conclusions:Arthroscopic limited excision of FHL tendon sheath combined with open technique of posterior ankle joint capsule is an effective and feasible surgery, which realizes accurate and minimally invasive treatment process and good short-term clinical effect.

Objective:To evaluate the utility of neoadjuvant vesical imaging-reporting and data system (NeoVI-RADS) in predicting tumor residuals and diagnosing muscle-invasive bladder cancer (MIBC) in patients undergoing neoadjuvant therapy, as well as its application in prognostic stratification.Methods:A retrospective case series analysis was conducted on the clinical data of 91 patients with bladder cancer who received neoadjuvant therapy at the Department of Urology, First Affiliated Hospital of Nanjing Medical University from July 2014 to June 2024. There were 84 male cases and 7 female cases, with an age of (66±9) years (range:45 to 85 years). The clinical staging of the patients was ≥T2 based on imaging. All of them underwent three or more cycles of neoadjuvant therapy, and had post-treatment multiparametric MRI (mp-MRI) evaluation. Based on the results of mp-MRI, the NeoVI-RADS was established and employed to assess tumor residuals and muscle invasion. The receiver operating characteristic curve was plotted, and the area under the curve (AUC) was calculated. Kaplan-Meier survival curves based on overall survival (OS) and cancer-specific survival (CSS) were plotted, and the Log-rank test was used for survival analysis comparison between groups.Results:In the neoadjuvant treatment cohort, the AUC for predicting tumor residuals post-neoadjuvant therapy using NeoVI-RADS was 0.900, with an accuracy of 93.4%, sensitivity of 95.8%, and a specificity of 85.0%. The NeoVI-RADS demonstrated strong diagnostic performance for MIBC, achieving an AUC of 0.900. At a NeoVI-RADS score cutoff of 4, the accuracy was 84.5%, with a sensitivity of 87.5% and a specificity of 72.9%. Additionally, compared to patients with NeoVI-RADS scores of 0 (5-year OS and CSS rates both 100%) or scores of 1 to 3 (5-year OS and CSS rates both 90.9%), patients with scores of 4 to 5 had significantly worse OS (5-year rate 63.0%) and CSS (5-year rate 66.3%) (all P<0.05). There was no statistically significant difference in OS or CSS between patients with NeoVI-RADS scores of 0 and those with scores of 1 to 3 (all P>0.05). Conclusion:NeoVI-RADS demonstrates significant diagnostic and prognostic value in the context of neoadjuvant treatment for bladder cancer, effectively assessing tumor residuals and muscle invasion, thereby enhancing patient management and facilitating personalized treatment approaches.

This article, integrating the latest evidence-based medical findings with recommendations from both domestic and international guidelines as well as clinical practice experience, discusses key issues related to renal replacement therapy (RRT) for early acute kidney injury (AKI) following transplantation. These include the timing of RRT initiation, treatment dose, anticoagulation strategy, timing of discontinuation, and intraoperative RRT. The aim is to optimize RRT management, standardize clinical protocols, and ultimately improve the prognosis of transplant recipients.

Asthenospermia is one of the important causes of male infertility,and its etiology and pathogenesis are complex.Traditional Chinese medicine(TCM)offers unique advantages in treating this disease.The"kidney deficiency and toxic-stasis"theory reveals the dynamic relationship between kidney essence deficiency and the interaction of toxic-stasis in disease pathogenesis,which can be applied clinically to guide the differentiation and treatment of asthenospermia.The formation of asthenospermia is closely related to the deficiency of kidney essence and the blockage of toxic stasis.The kidney essence is the source of reproductive essence.If the kidney essence is depleted for a long time and the kidney essence is deficient,the essence chamber cannot be enriched,resulting in spermatozoa dysfunction and poor spermatozoa mobility.The poison stasis interferes with the spermatozoa and turns into spermatotoxin,which directly harms spermatozoa fertility and leads to the decrease of spermatozoa mobility.Tongjing Jiedu Formula takes tonifying kidney to supply essence,diuresis and detoxification,activating blood circulation and removing blood stasis as the treatment principle,focusing on tonifying kidney to fill essence and nourishing healthy qi to restore the nourishing effect of kidney essence,and also emphasizes clearing heat and detoxification,activating blood circulation and removing blood stasis,promoting diuresis and dredging collaterals to remove poisonous damp-heat and static blood and harmonize blood and vessel,improving spermatogenic environment and improving sperm vitality to help men have children.This article analyzes the application of Tongjing Jiedu Formula in treating asthenospermia from the perspective of"kidney deficiency and toxic stasis",aiming to provid new ideas and methods for the explanation of the pathogenesis of the disease and TCM treatment.