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:To evaluate the quality of test papers and to analyze students'mastery of knowledge through the analysis of test papers,so as to provide reference for the reform of test proposition and correction teaching.Methods:Using paper analysis software(Ver 2.0),the paper quality,the students'scores and the answers to the questions of the final exam paper of Physiology of grade 2021 students majoring in nursing were analyzed.Results:The composition of the test paper was consistent with the requirements of the teaching programme,the difficulty of subjective and objective test questions was moderate,the differentiation of subjective test questions was good,the differentiation of objective test questions was general,and the reliability and validity were good.The overall performance was basically normal distribution.The full score ratio of objective test questions was higher than that of subjective test questions,and the zero score test questions were mostly concentrated in chapter 10 and chapter 4.Conclusion:Test paper analysis can feedback the problems and shortcomings of test paper proposition and teaching process,promote the quality of test paper and teaching model innovation,and improve the quality of teaching.

Objective To study and compare the oral microbiota and metabolites of children with Henoch Schonlein purpura(HSP)to identify specific microbiota and metabolites related to this disease and elucidate the pathogenesis of HSP.Methods Three groups of qualified subjects were included,including 20 in the HSP group,20 in the HSP nephritis(HSPN)group,and 20 in the control group.Perform high-throughput 16S rRNA sequencing and metabolic profiling of saliva from each group to analyze the correlation between differential microbiota and differ-ential metabolites.Results(1)Compared with the control group,there was a significant difference in richness and diversity in the HSPN group(P＜0.05).At the same time,there was no significant difference in richness and diver-sity in the HSP group(P＞0.05).Compared with the HSP group,the abundance,and diversity of the HSPN group were significantly increased(P＜0.05).At the genus level,the proportion of Streptococcus in each group is the high-est.Compared with the control group,there was no significant correlation between the HSP group and the genus of bacteria.In contrast,the HSPN group showed a significant increase in the genera of Pseudomonas and Parabacteroi-des(P＜0.05).Compared with the HSP group,the abundance of Pseudomonas and Parabacteroides in the HSPN group was significantly increased(P＜0.05).(2)Compared with the control group,the HSPN group had 12 differen-tial metabolites involving nine metabolic pathways,such as phenylalanine metabolism;There was no significant dif-ference in metabolites and no metabolic pathway in the HSP group.Compared with the HSP group,the HSPN group has 15 differential metabolites involving nine metabolic pathways,such as phenylalanine metabolism.(3)In the HSPN and control groups,Pseudomonas and Parabacteroides negatively correlated with Phenylalanine metabolic pathway products.In the HSPN and HSP groups,Pseudomonas,Parabacteroides,and Phenylalanine metabolic path-way products were negatively correlated.The metabolites involved in phenylalanine metabolism in the oral cavity are 2-hydroxycinnamic acid,Phenylpyruvic acid,and N-acetyl-L-phenylalanine.Conclusion There is a significant dif-ference between HSPN and HSP children and healthy children.Streptococcus,Pseudomonas,and Parabacteroides may be one of the trigger factors of HSPN,and Phenylalanine metabolism may be one of the pathways in the patho-genesis of HSPN.Children with HSPN have a more pronounced imbalance in oral microbiota and greater differences in metabolic products than children with HSP.

Objective:To evaluate the impact of cold-air anesthesia on patients′ comfort and side effects during ablative fractional carbon-dioxide (CO 2) laser treatment for acnescars. Methods:Eighteen patients with atrophic acne scars treated with CO 2 laser were used as split-face comparative study with a cold-air device combined with 5% lidocaine cream on the left side of the face, and the right side as a control group treated with 5% lidocaine cream only. Symptoms and signs of patients were observed during treatment, immediately after treatment, 15 minutes, 30 minutes and 1 month after treatment. The score of patient′s comfort and incidence of adverse events was evaluated. Results:The results were obvious difference between each group. The surface temperature in combined group (33.1±1.3) showed significantly better results compared with other groups (36.9±0.4) during the operative period while the same result after the treatment immediately shown in the combined group (35.1±1.3) compared with other groups (36.4±0.2). The score of erythema shown that combined group (48.7±8.4) was significantly lower than that of the control group (54.8±8.0) ( P<0.05) as the score of exudation in combined group (6.2±1.6) was lower than that in the control group (7.8±1.6). There was significant statistical difference regarding scores of erythema between combined group (46.9±6.6) and control group (51.8±6.9) a month after the treatment. The pigmentation score revealed the same result that the combined group (48.9±8.8) was lower than the other groups (51.4±7.0). No patients had severe adverse events. Conclusions:The cold-air cooling application is safe and effective to reduce the surface temperature, pain and side effects during fractional carbon-dioxide laser treatment.

Objective:To understand the molecular transmission characteristics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome(AIDS) patients in the mountainous area of southwest Zhejiang Province(Lishui city).Methods:A total of 147 blood samples were collected from newly-diagnosed HIV-1 infected who received no antiviral therapy, and pol gene was amplified, followed by sequencing. MEGA6.0 software was used to construct phylogenetic tree and determine gene subtypes. HIVDB online was used to analyze drug resistance mutation, then the pairwise genetic distance(GD) was calculated and the opitimal threshold of GD was selected, finally the molecular transmission network was constructed by Cytoscape3.7.0 software. Chi-square or Fisher′s exact probability method was used for statistical analysis. Results:A total of 134 sequences were obtained successfully, and nine subtypes were detected. The dominant subtypes were CRF08_BC (34.33%, 46/134), CRF01_AE (29.85%, 40/134) and CRF07_BC (23.88%, 32/134). It also found that age, registered residence, education level and transmission route had significant differences in distribution of subtypes ( P<0.05). Nineteen drug resistance individuals were found, and the total drug resistance rate was 14.18% (19/134). The HIV-1 molecular transmission network was plotted based on 1.2% GD threshold. A total of 15 transmission clusters (cluster size ranging from 2 to 29) were found. The network access rate was 49.25% (66/134), mainly including male (75.76%, 50/66), heterosexual (81.82%, 54/66) and patientsrinfected with CRF08_ BC (50.00%, 33/66). A transmission cluster including two cases of female sex workers and seven cases of drug resistance was identified, in which the average age of the patients was 57.21 years old and the average degree value was 22.7, and the cases were mainly infected through heterosexual contact (96.55%, 28/29). The highest homology of the sequences in the cluster was in Yunnan. Conclusions:The HIV-1 subtypes were diverse in the mountainous area of southwest Zhejiang Province(Lishui city). Drug resistant transmission had reached a moderate epidemic level. There were molecular transmission clusters with the aggregation characteristics of elderly clients in specific regions. It was urgent to formulate and implement precise intervention strategies to curb the spread of HIV.

Since 2010, the incidence of severe fever with thrombocytopenia syndrome (SFTS) has been increased. Owing the progress in diagnosis and treatment, the overall mortality of SFTS in China has decreased, while the mortality in critical SFTS patients is still high. In order to provide guidance and working procedures for clinicians to diagnose and treat critical SFTS, the National Medical Center for Major Public Health Events invited experts to discuss and formulate this consensus based on their experience and up-to-date knowledge on SFTS.

Objective:To analyze the long-term prognosis and prognostic factors of allergic bronchopulmonary aspergillosis(ABPA) in children suffering from cystic fibrosis (CF).Methods:An observational study was performed.All children who were admitted to the Department of Respiratory, Beijing Children′s Hospital, Capital Medical University from August 2014 to June 2018, with more than 2 years of followed up for the diagnosis of CF accompanied by ABPA were involved.Results:Three children met the inclusion criteria, with 2 boys and 1 girl, and their diagnostic age were 14, 8 and 9 years old, respectively.The follow-up duration ranged from 2 to 6 years.All the 3 cases were treated with systemic corticosteroids and antifungal agent.In case 1, the initial dose of prednisone was 0.75 mg/(kg·d), and the course of treatment was more than 5 years.The corticosteroid-dependent patient suffered from expectoration and chest pain, and radiographic findings indicated exacerbation, while his lung function was normal.Treating with initial dose of prednisone 2 mg/(kg·d) for 9 months, case 2 had normal serum immunoglobulin E(IgE) concentration, but his pulmonary artery was infiltrated by lesions, thus leasing to lobectomy.In case 3, the initial dose of prednisone was 0.6 mg/(kg·d), and the course of treatment was 18 months.And she developed persistent hypoxemia, and decreased pulmonary function, so lung transplantation was necessary 2 years after diagnosis.Conclusions:Systemic glucocorticoid combined with antifungal therapy is the main treatment for CF with ABPA, but there are individual differences in the efficacy.The level of serum total IgE is not always consistent with lung function and chest images.The overall prognosis is poor, and it is infeasible to evaluate the prognosis by single factor.