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.

The early angiopathy of systemic sclerosis (SSc) is a key hub connecting inflammation and fibrosis. The animal models that simulate the pathological characteristics of SSc are of great significance to study the etiology, pathogenesis and treatment of SSc with vascular involvement. This review of the characteristics of different animal models of SSc with vascular involvement provides a reference for relevant researchers to select appropriate models in the process of exploring the pathogenesis of SSc with vascular involvement.

Objective To describe and evaluate the clinical studies of postoperative pain sensitization caused by sleep deprivation through the evidence map system,understand the distribution of evidence in this field,and provide reference for subsequent evidence research.Methods A computer-based search of PubMed,EMBASE,Cochrane library,Web of Science,CNKI,Wanfang Data,VIP and Chinese Biomedical Literature Database from inception to August 2023 was conducted to obtain intervent ion studies,observational studies and systematic reviews/Meta-analysis of postoperative pain sensitization caused by sleep deprivation.The research characteristics and methodological quality were analyzed and evaluated.The Cochrane Handbook for Systematic Reviews,the Newcastle-Ottawa Scale(NOS)and the AMSTAR-2 scale were used to evaluate the quality of the included studies,and the evidence was comprehensively analyzed and displayed by means of bubble chart,table and text.Results A total of 35 observational studies(31 cohort studies and 4 case-control studies),15 randomized controlled trials and 4 systematic reviews/Meta-analyses were included.The number of publications increased rapidly after 2018 and peaked in 2022,and clinical studies in this field mainly fo-cused on cohort studies,with fewer randomized controlled trials and systematic reviews/Meta-analysis studies.The results of the evidence map showed that in terms of quality,22 studies were'high quality',24 studies were'medium quality',and 8 studies were'low quality'.Thirty studies showed that sleep deprivation could induce postoperative pain sensitization.Only 2 studies suggested that sleep disorders were not significantly asso-ciated with postoperative pain sensitization,and ten studies were uncertain whether sleep deprivation could in-duce postoperative pain sensitization.Conclusions Overall evidence shows that sleep deprivation can induce postoperative pain sensitization,but the evaluation dimensions are limited and the methodological quality of the included literature needs to be improved.More high-quality,large-sample and standardized clinical studies should be carried out in the future to provide better scientific basis for clinical work.

Objective:To compare the effects of manual acupuncture(MA),electroacupuncture(EA),and moxibustion on knee joint cartilage morphology,serum inflammatory factors interleukin(IL)-6 and IL-10,matrix metalloproteinase 13(MMP13),and intestinal flora composition in knee osteoarthritis(KOA)model rats.Methods:Forty male specific-pathogen-free Sprague-Dawley rats aged seven weeks were randomly divided into a normal group(n=8)and a KOA modeling group(n=32).The KOA model was established using sodium iodoacetate induction.The KOA modeling rats were further randomly divided into a model group,an MA group,an EA group,and a moxibustion group,with 8 rats in each group.In the MA,EA,and moxibustion groups,interventions targeting the right Futu(ST32)and Zusanli(ST36)were performed for 15 min,once every other day,for 14 sessions.The normal and model groups were bundled on the self-made fixation frame for 15 min.The rat knee joint diameter was measured on the 8th day of adaptive feeding,after successful modeling,and after the 14th intervention.Lequesne behavioral scoring was performed after successful modeling and after the 14th intervention.After the 14th intervention,hematoxylin-eosin(HE)staining and Masson staining were performed with the cartilage sections of the right knee joint.The pathomorphological changes of the rat joint cartilage were observed and quantified by Mankin's score.Enzyme-linked immunosorbent assay was used to detect the rat serum levels of IL-6,IL-10,and MMP13.Additionally,16S rDNA sequencing was used to detect the composition of rat fecal flora.Results:Compared to the normal group,the right knee joint diameter and the Lequesne score were significantly increased in the model group(P<0.01).Compared to the model group,the right knee joint diameter and the Lequesne score of rats in the MA,EA,and moxibustion groups were significantly reduced(P<0.01),with no significant differences among the three intervention groups(P>0.05).HE staining and Masson staining revealed disordered cartilage structure in the model group,which was improved following interventions in the MA group,EA group,and moxibustion group.Mankin's score was significantly higher in the model group versus the normal group(P<0.05)while significantly lower in the MA,EA,and moxibustion groups versus the model group(P<0.05).Serum analysis showed elevated IL-6 and MMP13 levels and reduced IL-10 level in the model group versus the normal group(P<0.05).Compared to the model group,the serum IL-6 level was significantly reduced(P<0.05),and the IL-10 level was significantly increased(P<0.05)in the MA,EA,and moxibustion groups,but without statistical differences among the three intervention groups(P>0.05);moreover,the MMP13 level in the moxibustion group was significantly lower than that in the model group(P<0.05).The alpha diversity analysis of intestinal flora showed no statistical difference in the number of operational taxonomic units(OTUs)and alpha diversity index among groups(P>0.05).Intestinal flora beta diversity analysis revealed significant differences among groups(P<0.05).Intestinal flora composition analysis showed significantly increased relative abundance of Lactobacillus(P<0.05)and significantly decreased relative abundance of Eubacterium_coprostanoligenes(P<0.05)in the model group compared to the normal group;compared to the model group,the relative abundances of Firmicutes,Lactobacillus,and Romboutsia in the MA,EA,and moxibustion groups were significantly reduced(P<0.05);the relative abundance of Bacteroidetes and Lachnospiraceae_NK4A136 in the MA group increased significantly(P<0.05);Bacteroidetes and Ruminococcaceaae_UGC-005 increased significantly in the moxibustion group(P<0.05).Conclusion:MA,EA,and moxibustion effectively reduced knee joint swelling,improved cartilage tissue morphology,optimized intestinal flora composition,down-regulated expression levels of serum pro-inflammatory factors IL-6 and MMP13,and increased expression level of anti-inflammatory factor IL-10 in KOA rats.Among them,moxibustion exhibited the most obvious regulatory effect on inflammatory factors.

Objective:To analyze the efficacy and prognostic factors of fractionated stereotactic radiotherapy (FSRT) for patients with breast cancer brain metastases (BCBM).Methods:Medical records and follow-up data of BCBM patients who underwent FSRT in Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center and Shenzhen People's Hospital from August 2019 to May 2023 were collected. The R Studio platform of the R version 4.2.1 statistical software was applied to analyze patients' baseline characteristics, 1- and 2-year local brain control (LBC), overall survival (OS) and distant brain control (DBC) and corresponding median failure-free survival, draw survival curve using Kaplan-Meier method. Prognostic factors were screened by univariate analysis and multivariate analysis (Cox regression).Results:Cumulatively, 52 patients (163 metastases in total) had a median survival follow-up of 22.1 months, 83% were<60 years old. Molecular typing: 13 cases (25%) were positive for human epidermal growth factor receptor 2 (HER2+) / hormone receptor negative (HR-), 2 cases (4%) were luminal A, 26 cases (50%) were luminal B, and 11 cases (21%) were triple negative. The median number of brain metastases was 2 (range: 1 - 17). Follow-up outcomes: the median OS was 34.0 months, with 1- and 2-year OS rates of 85.6% and 65.4%, respectively; the median LBC was 20.6 months, with 1- and 2-year LBC rates of 79.2% and 45.2%, respectively; and the median DBC was 10.3 months, with 1- and 2-year DBC rates of 46.7% and 28.9%, respectively. During follow-up, 13 patients underwent salvage local therapy (10 FSRT); 5 developed radiation necrosis (1 symptomatic). Prognostic factor analysis: absence of extracranial organ metastases (compared with ≥3) was a protective factor for OS, P<0.05. For LBC, fewer (1 - 2) extracranial organ metastases (compared with ≥3), and single brain metastasis (compared with ≥2) were favorable prognostic factors , while N 3 staging upon initial diagnosis was a poor prognostic factor (all P<0.05). For DBC, brain metastasis after surgery was a good prognostic factor, while complicated with lung metastasis and asymptomatic brain metastasis at the first diagnosis were poor prognostic factors (all P<0.05). Conclusions:FSRT yields relatively good LBC and poor DBC for BCBM patients. A certain percentage of patients require salvage FSRT during follow-up, but OS is maintained acceptable and the radiation necrosis is tolerable. Among the prognostic factors, the absence of extracranial metastatic organs is a good prognostic factor for OS; patients with single brain metastasis, fewer extracranial metastatic organs, and non-N 3 staging upon initial diagnosis can obtain better LBC after FSRT.

Objective:To investigate the prevalence and influencing factors of depression,anxiety and comorbid depression-anxiety symptoms among college freshmen,providing a theoretical basis for promoting their mental health.Methods:From Jan to Feb 2022,an online questionnaire survey was conducted,involving 483 online questionnaires from college freshmen(184 males,299 females).The depression-anxiety-stress self-rating scale,smartphone dependence self-rating scale for adolescents,and Pittsburgh sleep quality index(PSQI)were used for online surveys.The influencing factors of depression,anxiety,and their comorbidity among college freshmen were analyzed by multivariable logistic regression analysis.Results:The detection rates of smartphone dependence,sleep disorders,depression,anxiety and comorbid depression-anxiety symptoms among college freshmen were 26.1%,12.8%,26.3%,32.1%,and 23.6%,respectively.The detection rates of depression,anxiety and comorbid depression-anxiety symptoms in male students were significantly higher than those in female students(P＜0.05).Multivariable logistic regression analysis showed that self-perceived poor mental health,smartphone dependence and sleep disorders were risk factors for depression,anxiety and comorbid depression-anxiety symptoms.Low satisfaction with college life was a risk factor for depression.Medical specialty was a risk factor for anxiety and comorbid depression-anxiety symptoms(P＜0.05).Conclusions:Male college freshmen show higher rates of depression,anxiety,and their comorbidity.Low satisfaction with college life,self-perceived poor mental health,high academic pressure,smartphone dependence,medical specialty,and sleep disorders may be risk factors for depression,anxiety and comorbid depression-anxiety symptoms among college freshmen.

Objective:To analyze pancreatic cancer incidence and mortality data in China and worldwide and to provide data for pancreatic cancer prevention and control efforts.Methods:Data of pancreatic cancer incidence and mortality rates, along with historical and predictive data, were obtained from the GLOBOCAN 2022 database. Epidemiological characteristics of pancreatic cancer was analyzed by region, sex, age and Human Development Index (HDI). Spearman's correlation coefficient test was used to assess the relationship between HDI and age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR).Results:In 2022, the global number of new cases and deaths of pancreatic cancer will be 511 thousand and 467 thousand, respectively, with an ASIR and ASMR of 4.7/10 5 and 4.2/10 5, respectively. North America and Europe had the highest pancreatic cancer incidence and mortality rates of 8.5/10 5 and 7.3/10 5, respectively. Global ASIR and ASMR in men were both 1.4 times higher than those in women. HDI levels were positively correlated with ASIR ( r=0.79, P＜0.001) and ASMR ( r=0.78, P＜0.001) of pancreatic cancer in all regions. The number of pancreatic cancer cases and deaths in China were 119 thousand and 106 thousand, respectively, while the ASIR and ASMR of pancreatic cancer were 4.4/10 5 and 3.9/10 5, respectively. Both ASIR and ASMR in men were both 1.5 times higher than those in women in China. The number of pancreatic cancer incidence and death cases in China in 2050 is predicted to be 216 thousand and 204 thousand cases, with an increase of 81.5% and 92.5% compared with 2022, respectively. Conclusions:The disease burden of pancreatic cancer varies significantly among different regions, genders and ages. Pancreatic cancer incidence and mortality are positively correlated with HDI. The incidence and mortality rates of pancreatic cancer in China are close to the global average, but the number of new cases and deaths is high. Prevention and control should be strengthened to improve the survival of pancreatic cancer patients.

Objective:To investigate the hospitalization utilization of pneumoconiosis patients and its influencing factors in a northwestern city, and to provide theoretical basis for formulating service policies for pneumoconiosis patients.Methods:From March to October 2021. Existing living pneumoconiosis patients in kashgar were selected as the research objects. The "Survey Questionnaire on Medical Behaviors and Influencing Factors of Pneumoconiosis Patients" developed by the National Institute of Occupational Health and Poison Control of China Centers for Disease Control and Prevention was used to collect pneumoconiosis patients infomations from March to October 2021. This study investigated the demographic characteristics of pneumoconiosis patients, the types and stages of pneumoconiosis, as well as hospitalization in the past year, reasons for hospitalization, treatment measures, reasons for discharge. Additionally, it examined factors influencing medical behaviors, including medical insurance reimbursement, work-related injury insurance, and compensation situations.Logistics regression was used to analyze the influencing factors of hospitalization utilization.Results:The average age of the pneumoconiosis patients was elder with the age of 64.8. 86.7% (156/178) of them were retired, 75.8% (135/178) of them relied primarily on pensions for their income. The main types of pneumoconiosis were silicosis and coal workers' pneumoconiosis with the proportion of 57.3% (102/178) and 24.2% (43/178). 67.4% of them were stage I. The hospitalization rate in the year prior to the survey was 37.1%. The factors that promoted hospitalization were pension as the main source of income, pneumoconiosis in stage II, silicosis as the pneumoconiosis type, suffering joint pain, with two OR more other lung diseases (tuberculosis, cor pulmonale, COPD, pulmonary infection, bulla or pneumothorax, lung cancer, or mesothelioma) ( P<0.05) . Conclusion:The hospitalization rate of pneumoconiosis patients in the previous year was low. It is mainly influenced by the patient's economic income, the duration of pneumoconiosis, and the presence of comorbidities.

Objective:To investigate the effects of three surgical methods on anorectal dynamics indexes, pain symptoms and postoperative complications in patients with moderate to severe mixed hemorrhoids.Methods:Eighty patients with moderate to severe mixed hemorrhoids diagnosed and treated in Tongling People′s Hospital from March 2021 to December 2022 were retrospectively selected as the study objects, and they were divided into mucosal resection group (30 cases), sphincterotomy group (30 cases) and mixed hemorrhoidal resection group (20 cases) according to the treatment methods. The basic conditions of operation, anorectal dynamics indexes, pain symptoms and postoperative complications were compared among the three groups.Results:The operative time, intraoperative blood loss, first postoperative defecation time, postoperative bed time and hospital stay in the mucosa resection group were all shorter than those in the sphincterotomy group and the mixed hemorrhoidectomy group:(20.57 ± 5.85) min vs. (24.68 ± 4.66) and (33.86 ± 4.27) min, (4.19 ± 0.54) ml vs. (6.34 ± 0.82) and (9.25 ± 1.39) ml, (1.57 ± 0.12) d vs. (1.95 ± 0.32) and (2.48 ± 0.54) d, (1.43 ± 0.35) d vs. (1.64 ± 0.41) and (1.90 ± 0.44) d, (4.57 ± 0.39) d vs. (5.83 ± 0.47) and (7.64 ± 0.55) d, there were statistical differences ( P<0.05). The above indexes in the sphincterectomy group were shorter than those in the mixed hemorrhoidectomy group, there were statistical differences ( P<0.05). The maximum rectal volume threshold (RMTV), rectal perception threshold (RSTV) and maximum rectal systolic blood pressure (MASP) in the resection group were higher than those in the sphincterotomy group: (201.59 ± 40.13) ml vs. (178.45 ± 38.59) ml, (65.54 ± 18.29) ml vs. (54.62 ± 20.39) ml, (126.36 ± 12.29) mmHg (1 mmHg = 0.133 kPa) vs. (42.23 ± 14.46) mmHg, anal canal resting pressure (RASP) was lower than that in the sphincterotomy group: (32.59 ± 10.25) mmHg vs. (63.50 ± 13.69) mmHg, there were statistical differences ( P<0.05). The RMTV and RSTV in the sphincterotomy group were higher than those in the mixed hemorrhoidectomy group: (178.45 ± 38.59) ml vs. (135.85 ± 35.68) ml, (54.62 ± 20.39) ml vs. (41.34 ± 20.55) ml, the RASP and MASP were lower than those in the mixed hemorrhoidectomy group :(63.50 ± 13.69) mmHg vs. (73.33 ± 15.69) mmHg, (42.23 ± 14.46) mmHg vs. (128.66 ± 16.33) mmHg, there were statistical differences ( P<0.05). The postoperative visual analogue scale (VAS) score in the mucosa resection group were lower than those in the sphincterotomy group and the mixed hemorrhoidectomy group: (1.57 ± 0.25) score vs. (2.57 ± 0.36) and (3.42 ± 0.52) score, there were statistical differences ( P<0.05). The VAS scores in the sphincterectomy group was lower than that in the mixed hemorrhoidectomy group, there was statistical difference ( P<0.05). The incidence of postoperative complications in the mucosa resection group was lower than that in the sphincterectomy group: 3.33% (1/30) vs. 20.00% (6/30), and the incidence of postoperative complications in the sphincterectomy group was lower than that in the mixed hemorrhoidectomy group: 20.00% (6/30) vs. 50.00% (10/20), there were statistical differences ( χ2 = 4.04, 4.96, P<0.05). Conclusions:Compared with partial internal anal sphincterotomy and external stripping and internal ligation of mixed hemorrhoids, partial rectal mucosal resection is more effective in the treatment of Ⅲ~Ⅳ grade mixed hemorrhoids, which can effectively restore anorectal dynamic indexes, reduce postoperative pain and reduce the occurrence of complications.

Objective To investigate the potential therapeutic targets and underlying molecular mechanisms of Z-ligustilide(Z-LIG)in treating retinitis pigmentosa(RP).Methods By integrating multiple databases,such as GeneCards and TargetNet,common targets for RP and Z-LIG were identified.Protein-protein interaction(PPI)network analysis of the targets was conducted using the STRING database and analyzed in Cytoscape to identify core targets.The DAVID database was employed for the functional enrichment analysis of Gene Ontology(GO)and the pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)for the core targets.The PubChem database was accessed for molecular docking verification to validate the binding affinity between Z-LIG and the core targets.Finally,male rd10 mice were randomly divided into a control group(n=5)and a Z-LIG treatment group(n=5).The protective effect of Z-LIG on the visual function in rd10 mice was verified through visual electrophysiology and behavioral tests.Western blotting and RT-qPCR were utilized to investigate the molecular mechanism of action.Results A total of 66 shared targets between RP and Z-LIG were identified through the screening process.PPI network analysis identified 55 key targets.GO enrichment analysis yielded 623 terms,which covering 3 dimensions,including cellular component(CC),molecular function(MF),and biological process(BP),such as inflammatory response.KEGG pathway enrichment analysis further concentrated 124 terms,which were enriched in the PI3K-Akt signaling pathway.Molecular docking suggested that Z-LIG could specifically bind with high affinity to RP-related core targets(such as EGFR and STAT3)via hydrogen bonds.In animal experiments,compared to the control group,the rd10 mice from the Z-LIG group showed a greater preference for the dark environment in the light/dark transition test(P<0.05),exhibited significantly higher amplitudes of A-wave and B-wave in electroretinogram(ERG)(P<0.05),greater number of outer nuclear layers,with fewer apoptotic cells and less microglial activation(P<0.05),demonstrated obviously reduced protein levels of p-PI3K/PI3K and p-AKT/AKT in the retina(P<0.05),and had notably down-regulated mRNA levels of pro-inflammatory cytokines IL-1β and IL-6(P<0.05).Conclusion Z-LIG may exert a protective effect on the retina of rd10 mice by inhibiting the activation of the PI3K/AKT-inflammatory axis,thereby delaying retinal degeneration.