ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

Objective:According to the international cooperation project of Peking University Cancer Hospital on human genetic resource management practices, combined with the development direction of human genetic resource management laws and regulations, and propose reference suggestions for medical institutions to strengthen human genetic resource management.Methods:Sort out the projects that Peking University Cancer Hospital obtained international cooperation approval on the government platform of the Ministry of Science and Technology from July 2019 to June 2023, analyze the current situation of human genetic resource management in the hospital, summarize the challenges brought by the implementation of new regulations on human genetic resource management in medical institutions, and propose corresponding suggestions.Results:A total of 1276 international cooperation projects on human genetic resources have been approved, including 345 initial declarations and 931 change declarations. Involving 453 studies, including 286 clinical trials of drugs or devices on the market, accounting for 63.13%, and 100 clinical trials of Phase I drugs, accounting for 34.97% of the market studies. On average, there are 3.14 changes per project for listed research, and 1.56 changes per project for non listed research.Conclusions:Regulations on the Management of Human Genetic Resources ( short for Rules) limit the management scope of international cooperation projects involving human genetic resources and delegate management authority to medical institutions. Adjusting the scope of application for international cooperative clinical trial filing may result in some administrative approval projects being transferred to filing. The approval process for international cooperative scientific research projects on human genetic resources has been adjusted. Suggest medical institutions to strengthen the management of samples and intellectual property outside the scope of application of Rules.Strengthen the entire process management of international cooperation in scientific research. Pay attention to and timely communicate the dynamics of human genetic resource management.

With the continuous development of medical science and the widespread use of antibiotics,the problem of bacterial resistance is increasing,especially the increasing carbapenem-resistant Enterobacteriaceae(CRE)infection,and the high mortality rate,which brings great challenges to clinical treatment.In this paper,the mechanism of drug resistance,existing antibac-terial drugs,and exploratory treatment options for CRE are reviewed,and the research progress in treating CRE infection is dis-cussed to provide more reliable evidence and a theoretical basis for clinical practice.

Objective To analyze the effects of three sterilization methods,namely,pressure steam,low-temperature plasma and ethylene oxide,on the magnetic flux of magnetic surgical devices and their sterilization costs.Methods A total of 234 magnetic surgical devices of different specifications and models(magnetic rings)were randomly divided into Group A,Group B and Group C after the paired number was labelled,and each group consisted of 78 pieces(39 pairs).After packaging each pair of devices according to sterilization specifications,Group A was sterilized by pressure steam,Group B was sterilized by low-temperature plasma,and Group C was sterilized by ethylene oxide.We measured the magnetic flux of three sets of magnetic rings before and after sterilization,and comparatively analyzed the sterilization cost and sterilization time of the single package.Results There was no statistically significant difference in the impact of the three sterilization methods on the magnetic flux of the magnetic surgical devices(P＞0.05),but there was a significant difference in the magnetic flux before and after sterilization for each sterilization method(P＜0.001);the sterilization cost was(1.96±0.16)yuan for Group A,(23.17±0.32)yuan for Group B,and(8.16±0.18)yuan for Group C,showing statistically significant differences among the three groups(P＜0.01).The sterilization time was(65.21±3.36)min for Group A,(45.46±1.39)min for Group B,and(1020.38±12.21)min for Group C,with statistically significant differences among the three groups(P＜0.01).Conclusion None of the three sterilization methods affects the magnetic flux of the magnetic surgical devices.Pressure steam method shows the lowest cost of single package,low-temperature plasma method shows the highest cost of single package,while ethylene oxide method shows the highest sterilization time.Pressure steam should be the preferred sterilization method for magnetic surgical devices.

Objective To evaluate the clinical value of neutrophil CD64(nCD64)index as a novel biomark-er in the differential diagnosis of acute and chronic brucellosis.Methods A total of 38 patients with acute bru-cellosis and 48 patients with chronic brucellosis diagnosed in the People's Hospital of Xinjiang Uygur Autono-mous Region from February 2021 to July 2023 were included.Peripheral blood of the patients was collected and nCD64 index was detected by flow cytometry,and the correlation between nCD64 index and disease severi-ty was analyzed.Receiver operating characteristic(ROC)curve was used to analyze the sensitivity and the specificity of nCD64 index in differentially diagnosing acute and chronic brucellosis.Meanwhile,Rose-Bengal Plate Test(RBPT)and Standard Tube Agglutination Test(SAT)were used as controls to evaluate the clini-cal diagnostic value of the three.Results The nCD64 index of acute brucellosis patients was higher than that of chronic brucellosis patients(U=216.00,P<0.001),and the index was positively correlated with the sever-ity of the disease(r=0.670,P<0.001).The ROC curve analysis results showed that the area under the curve of nCD64 index in the differential diagnosis of acute and chronic brucellosis was 0.882(95%CI:0.811-0.952,P<0.001),the cut-off value was 2.81,and sensitivity,specificity,positive predictive value,negative predictive value and accuracy were 83.3%,81.6%,80.4%,81.9%and 82.6%,respectively.The efficacy of nCD64 index in differential diagnosis of nCD64 index was significantly better than those of the qualitative tests of RBPT and SAT.Conclusion nCD64 index has favourable sensitivity and specificity in the differential diag-nosis of acute and chronic brucellosis,and tends to reflect the severity of the disease.It has clinical value in the differential diagnosis of acute brucellosis and chronic brucellosis,and plays an important role in the early diag-nosis and treatment effect monitoring of brucellosis.

Objective To investigate the characteristics of changes in interleukin(IL)-33 and regulatory T(Treg)cells in brucellosis,to verify the regulatory effect of IL-33 on Treg cells,so as to clarify the immune mechanism of IL-33 on Treg cells in brucellosis.Methods The peripheral blood of 39 patients with brucellosis treated in the People's Hospital of Xinjiang Uygur Autonomous Region from January to December 2021(the brucellosis group)and 42 healthy controls(the healthy control group)who underwent physical examination during the same period were collected.The serum IL-33 level was detected by AimPlex kit,and the proportion of Treg cells was detected by flow cytometry.Peripheral blood mononuclear cell(PBMC)was extracted and cultured in vitro to observe the proportion and mRNA expression levels of forkhead box protein P3(Foxp3)after stimulation and blocking of IL-33.Results Compared with the healthy control group,the level of IL-33 and the proportion of Treg cells in brucellosis group were significantly increased,with statistical significance(P＜0.05).In vitro tests showed that the Foxp3 proportion and mRNA expression level of PBMC in the two groups were significantly increased after IL-33 stimulation,and significantly decreased after IL-33 blocking,with statistical significance(P＜0.001).Conclusion IL-33 and Treg cells increased significantly in brucellosis patients,and IL-33 promoted the immune function of Treg cells.Blocking IL-33 is expected to be a potential target for immunotherapy of brucellosis.

Objective:To investigate the clinical efficacy of laparoscopic radical resection of hilar cholangiocarcinoma (LRHCCA).Methods:The retrospective and descriptive study was constructed. The clinicopathological data of 211 patients who under LRHCCA in the Second Hospital of Hebei Medical University from May 2014 to June 2022 were collected. There were 135 males and 76 females, aged (63±8)years. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. Results:(1) Surgical situations. All 211 patients underwent LRHCCA successfully, with the operation time as 350 (300,390)minutes, volume of intraoperative blood loss as 400(200,800)mL, and intraoperative red blood cell transfusion as 2.0(range, 0-15.0)U, respectively. As partial portal vein invasion, 10 of 211 patients underwent portal vein resection and reconstruction. Results of intraoperative histopathology examination showed negative margin of portal vein. The operation time, volume of intraoperative blood loss, intraopera-tive red blood cell transfusion of the 10 patients was (400±53)minutes, 1 200(range, 800-3 000)mL, 5.5(range, 4.0-15.0)U, respectively. (2) Postoperative situations. Of the 211 patients, there were 63 cases of the Bismuth type Ⅰ, 65 cases of the Bismuth type Ⅱ, 22 cases of the Bismuth type Ⅲa, 26 cases of the Bismuth type Ⅲb, 35 cases of the Bismuth type Ⅳ. The R 0 resection rate was 95.73%(202/211). There were 202 patients identified as adenocarcinoma of the bile duct, including 7 cases with poorly differentiated tumor, 189 cases with moderate to poorly differentiated tumor, 3 cases with moderate to well differentiated tumor, 3 cases with well differentiated tumor. There were 8 patients with poorly differentiated biliary mucinous adenocarcinoma, 1 patient with intraductal papillary neoplasm with high-grade epithelial dysplasia. There were 24 cases of stage Ⅰ, 98 cases of stage Ⅱ, 30 cases of stage ⅢA, 34 cases of stage ⅢB, 19 cases of stage ⅢC, 6 cases of stage ⅣA. Of the 211 patients, there were 25 cases with postoperative biliary fistula, 11 cases with postoperative abdominal infection, 3 cases with postoperative bleeding as anastomotic bleeding after biliary fistula, 2 cases with postoperative gastric emptying disability, 1 case with postoperative acute liver failure. There were 7 patients undergoing postoperative unplanned reoperation, including 3 cases with emergency operation for hemostasis, 4 cases with abdominal exploration debridement and drainage for severe abdominal infection. There were 3 cases dead during perioperative period, including 1 case of acute liver failure, 1 case of systemic infection and multiple organ failure, 1 case of exfoliated deep venous thrombosis of lower extremities and acute pulmonary embolism. The postoperative duration of hospital stay was (15±5)days of the 211 patients and (17±4)days of patients undergoing portal vein resection and reconstruction. The cost of hospital stay of the 211 patients was (11.7±1.7)ten thousand yuan. (3) Follow-up. Of the 211 patients, 188 patients were followed up for 21(range, 4?36)months. The median survival time of 188 patients was 22 months, and the postoperative 1-, 2- and 3-year survival rate was 90.9%, 43.1% and 18.7%, respectively. Conclusion:LRHCCA is safe and feasible, with satisfactory short-term effect, under the coditions of clinicians with rich experience in laparoscopic surgery and patients with strict surgical evaluation.