AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.

Objective To investigate the effect of sarcopenia on balance function in patients with Parkinson's disease(PD).Methods Sixty patients with PD diagnosed by our hospital from January 2021 to June 2021 were selected as the study objects.All patients were divided into myopenia group and control group according to the diagnostic criteria established by the Asian Working Group for Sarcopenia(AWGS)in 2014.The UPDRS Ⅲ,Berg balance scale,timed-up-go test and activity balance confidence scale were compared between the two groups.Results The grip strength,walking speed and RASM of the myopenia group were lower than those of the control group(P<0.05);Compared with the control group,the number of falls,UPDRS Ⅲ,Berg score and TUG duration in the myopenia group were significantly increased(P<0.05).The total score of ABC,ABC-2,ABC-3,ABC-5,ABC-6,ABC-7,ABC-8,ABC-9,ABC-11,ABC-14,ABC-15,ABC-16 in myopenia group were poor,and the differences were statistically significant(P<0.05).Further analyzing the differences between sex genders,we found that female sarcopenia had lower scores on ABC-2,ABC-3,ABC-8,ABC-9,ABC-11,ABC-13,ABC-14,ABC-15,ABC-16,and total score indexes,with statistically significant differences.Conclusion Myopenia significantly affects the balance function of PD and increases the risk of falls.

Objective:Analyzing the epidemic trends and spatio-temporal distribution characteristics of condyloma acuminatum in China from 2018 to 2023.Methods:Data of condyloma acuminatum cases and incidence rate including 31 provinces (autonomous regions and municipalities) from 2018 to 2023 were collected through the National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. Incidence trend analysis was conducted using Joinpoint 4.9.1 software, and spatial autocorrelation analysis using ArcGIS 10.5 software. Spatio-temporal scanning analysis was carried out with SaTScan 10.1.2 software.Results:The incidence rate of condyloma acuminatum declined from 7.26 per 100 000 in 2018 to 7.19 per 100 000 in 2023. The average annual percent change was -0.26%, which was no statistically significant downward trend ( t=-0.26, P=0.806). A significant positive global spatial autocorrelation was observed in the county-level incidence rate across the country, with the global Moran's I ranging from 0.55 to 0.60 (all P<0.001); the Getis-Ord General test statistic Z( G) was all >1.96, indicating a high-value clustering pattern in the reported incidence rate of condyloma acuminatum. The local spatial autocorrelation analysis detected 256, 244, 246, 284, 308, and 315 hotspots each year, which were mainly located in the provinces of Zhejiang, Fujian, Guangdong, Guizhou, Yunnan and Chongqing. Spatio-temporal scanning analyses identified 76 statistically significant spatiotemporal clusters covering 25 provinces (autonomous regions and municipalities). Conclusions:From 2018 to 2023, the reported incidence rate of condyloma acuminata in China exhibited a mild decline. The distribution of hotspot areas and spatiotemporal clusters was largely consistent, primarily in the southeastern coastal and southwestern regions.

Objective:To construct an evaluation indicator system for the efficiency of nursing human resources in integrated medical and elderly care institutions using Data Envelopment Analysis (DEA) and subsequently evaluate its effectiveness.Methods:This cross-sectional survey utilized literature review and investigative methods to initially establish a library of evaluation indicators for nursing human resource efficiency. The Delphi method was employed in two rounds of consultations with 17 experts from various fields, including nursing management, elderly care institution management, integrated medical and elderly care institution management, health economics management, and public health. The reliability of the indicator system was assessed based on factors such as expert enthusiasm, authority, concentration of opinions, and coordination. Adjustments, modifications, and improvements were made to the indicators based on expert opinions to establish the final indicator system. From August to December 2022, the DEA model was applied to evaluate the efficiency of 12 integrated medical and elderly care institutions in Haikou city based on this indicator system.Results:The constructed evaluation indicator system comprised 68 items divided into three levels: 9 primary indicators, 19 secondary indicators, and 40 tertiary indicators. The positive coefficients of the two rounds of expert consultations were 100% and 94.1%, with authority coefficients of 0.88 and 0.92, Kendall harmony coefficients of 0.471 and 0.348, and mean coefficients of variation of 0.16 and 0.12 ( P<0.001). DEA evaluation results for the 12 integrated medical and elderly care institutions showed that 5 were DEA effective institutions with comprehensive efficiency (OE), technical efficiency (TE), and scale efficiency (SE) values all equal to 1.000, while 7 were non-DEA effective institutions, including 4 with SE <1.000 but TE=1.000 and 3 with both SE and TE<1.000. Conclusions:The constructed evaluation indicator system demonstrates high enthusiasm, authority coefficients, and coordination in expert consultations, indicating high acceptability and comprehensive content with distinct levels and strong specialty characteristics. The DEA model′s evaluation results objectively and effectively reflect the efficiency of nursing human resources in integrated medical and elderly care institutions, demonstrating practical utility.

Objective To explore the difference of transfer RNA-derived small RNA(tsRNA)expression profile before and after acute myocardial infarction(AMI)and the diagnostic value of tsRNA for AMI.Methods Age-and weight-matched male C57 mice(8-10 weeks)were randomly divided into MI group and Sham group,with 4 in each group.AMI model was surgically induced in mice in MI group.After 24 h of modeling,RNA was extracted from left ventricular myocardial tissue.After removing modifications,total RNA of each sample was sequentially ligated to 3'and 5'small RNA adapters.Subsequently,reverse transcription PCR was performed.cDNA was then synthesized and amplified.The amplified products corresponding to the size of 15-40 nt RNA were screened to construct a library for sequencing.The sequencing results were compared with the mature tRNA and tRNA precursor sequences in GtRNAdb database.Differentially expressed tsRNA profiles before and after AMI were obtained.The alterations of the cleaved patterns of tRNA corresponding to the same codon before and after AMI were analyzed.According to the profile of differentially expressed tsRNA before and after AMI,tsRNA only abundantly expressed in MI group were selected and verified in myocardial tissue and plasma of mice to explore the potential of these tsRNAs as diagnostic markers of AMI.Results tsRNA profile showed good repeatability within the same group and great distinctiveness between the different groups.After AMI occurred,the cleaved patterns of a variety of tRNAs changed,including tRNA Asn-GTT,Glu-TTC,Gly-ACC,Gly-GCC,His-GTG,Ile-AAT,Ile-GAT,Pro-TGG,Ser-AGA,and Trp-CCA.Compared with the Sham group,268 tsRNAs significantly up-regulated and 1 228 tsRNAs down-regulated in MI group,and 64 tsRNAs were uniquely expressed in MI group.tRF-Gly-CCC-2-31,tiRNA-Val-CAC-1-32,tiRNA-Val-AAC-2-32,tiRNA-Glu-TTC-2-32,and tiRNA-Lys-TTT-1-34 were specifically expressed in cardiac tissue on the 1st day post AMI.Among them,tiRNA-Val-AAC-2-32 and tiRNA-Lys-TTT-1-34 showed specifically abundant levels in plasma from MI group and dynamically changed with AMI duration.Conclusions The expression profile of tsRNA is significantly different before and after AMI.tiRNA-Val-AAC-2-32 and tiRNA-Lys-TTT-1-34 are uniquely highly expressed in myocardial tissue and plasma from AMI mice,and might have the potential as diagnostic markers of AMI.

Objective:To explore the clinical and genetic characteristics of a neonate with Microvillus inclusion disease (MVID).Methods:A neonate with MVID admitted to the First Affiliated Hospital of Zhengzhou University in May 2019 was selected as the study subject. Clinical data were collected. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA). A literature was also carried out to summarize the clinical and genetic characteristics of MVID.Results:The prematurely born neonate had presented with unexplained refractory diarrhea and metabolic acidosis. Active symptomatic treatment was ineffective, and the child had died at 2 months old. WES revealed that he had harbored compound heterozygous variants of the MYO5B gene, namely c. 1591C>T (p.R531W) and deletion of exon 9. Sanger sequencing showed that the R531W variant was inherited form his father, and MLPA confirmed that the exon 9 deletion was inherited from his mother. Seven children with MVID were reported in China, of which one was lost during follow-up and six had deceased. One hundred eighty eight patients were reported worldwide and only one was cured. The clinical features of MVID had included refractory diarrhea, metabolic acidosis and poor prognosis. Conclusion:The child was diagnosed with MVID due to the compound heterozygous variants of the MYO5B gene, which has provided a basis for genetic counseling and prenatal diagnosis.

Objective To observe the effects of Gegen Qinlian Decoction on pancreatic endoplasmic reticulum stress in mice with type 2 diabetes mellitus(T2DM);To explore its mechanism of action in the treatment of T2DM.Methods Totally 75 SPF male db/db mice were randomly divided into model group,metformin group,and Gegen Qinlian Decoction high-,medium-,low-dosage groups,with 15 mice in each group.15 db/m mice were set as the blank group.The administration groups received corresponding medicine for gavage for 12 weeks.Body mass,fasting blood glucose(FBG)and glycated hemoglobin(HbA1c)in mice were detected,HE staining was used to observe the pathological changes of pancreatic tissue,the apoptosis of islet cells was determined by TUNEL staining,Western blot was used to detect pancreatic tissue glucose regulatory protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)protein expression,RT-PCR was used to detect pancreatic tissue PERK,ATF4,CHOP mRNA expressions.Results Compared with the blank group,the body mass,FBG and HbA1c contents in the model group significantly increased(P<0.01);the pancreatic tissue structure was incomplete,with blurry boundaries and vacuoles inside,leading to a significant increase in pancreatic islet cells apoptosis(P<0.01);the expressions of GRP78,p-PERK,ATF4,and CHOP proteins in pancreatic tissue significantly increased(P<0.01),and the mRNA expressions of PERK,ATF4 and CHOP significantly increased(P<0.01).Compared with the model group,the body mass,FBG and HbA1c contents of mice in each administration group significantly decreased(P<0.05,P<0.01);pathological changes in pancreatic tissue was reduced,and islet cells apoptosis decreased to varying degrees(P<0.05,P<0.01);the expressions of GRP78,p-PERK,ATF4 and CHOP proteins in pancreatic tissue significantly decreased(P<0.01)in Gegen Qinlian Decoction high-and medium-dosage groups and the metformin group,and the expressions of PERK,ATF4 and CHOP mRNA significantly decreased(P<0.05,P<0.01).Conclusion Gegen Qinlian Decoction may decreased pancreatic islet cells apoptosis,protect pancreatic cell function,and delay the progression of T2DM by inhibiting the endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathway,and down-regulating the expressions of related genes and proteins.

ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease （DKD） in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose （FBG）. Mice with FBG ≥ 16.7 mmol·L^-1， increased urine output， and persistent albuminuria were considered successful in model establishment. After successful modeling， they were randomly divided into a model group， a dapagliflozin group （1.5 mg·kg^-1·d^-1）， and high， medium， and low dose groups of Dahuang Tangluo pills （3.6， 1.8， 0.9 g·kg^-1·d^-1， respectively）， with eight mice in each group. All medication groups were administered orally， while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks， the survival status of the mice was observed， and their body weight， FBG， and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products （AGEs） and receptors for advanced glycation end products （RAGE） proteins. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were utilized to detect the gene and protein expression levels of AGEs， RAGE， inhibitor of nuclear factor-κB （NF-κB） kinase （IKK）， and NF-κB in the renal tissues of mice in each group. ResultCompared with control group， the model group showed a significant increase in body weight， FBG， serum creatinine （SCr）， urinary microalbumin/urine creatinine ratio （ACR）， total cholesterol （TC）， and triglycerides （TG） （P<0.05）. The levels of intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） in renal tissues were significantly elevated （P<0.05）. Renal histopathological staining and electron microscopy revealed loose arrangement， gaps， structural disarray， mesangial proliferation， and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE， IKK， and NF-κB genes in renal tissues （P<0.05）. Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues （P<0.05）. Western blot results showed a significant increase in the expression of AGEs， RAGE， IKK， and NF-κB proteins in renal tissues （P<0.05）. After drug intervention， compared with model group， the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight， FBG， SCr， and ACR （P<0.05）， and a significant decrease in TC in mouse serum （P<0.05）， while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum （P<0.05）. All treatment groups showed a significant reduction in ICAM-1， IL-6， and TNF-α in renal tissues （P<0.05）. Renal histopathological staining and electron microscopy showed improved kidney injury， decreased collagen fiber deposition， and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE， IKK， and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Western blot results showed a significant decrease in the expression of AGEs， RAGE， IKK， and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice， possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective To investigate the relationship between the therapeutic effect of anti-vascular endothelial growth factor(VEGF)and cytokines in aqueous humor in patients with diabetic retinopathy(DR).Methods From July 2023 to December 2023,50 DR patients(56 eyes)who were treated with anti-VEGF drugs in the Department of Ophthal-mology,the Third Affiliated Hospital of Xinxiang Medical University were included in this study.The patients were divided into the diabetic macular edema(DME)group(30 patients,36 eyes)and the proliferative DR(PDR)group(20 patients,20 eyes).Patients in the DME group received an intravitreal injection of aflibercept once a month for three consecutive times,with aqueous humor extracted before each injection.Patients in the PDR group received an intravitreal injection of aflibercept one week before vitrectomy,with aqueous humor extracted before injection and during vitrectomy,respective-ly.The concentrations of vascular endothelial growth factor A(VEGF-A),placental growth factor(PLGF),interleukin(IL)-1β,IL-23,IL-17A,and tumor necrosis factor-α(TNF-α)in the aqueous humor were detected using the Luminex as-say.Before injection therapy,all patients underwent best corrected visual acuity(BCVA)and central macular thickness(CMT)examinations,and their correlations with cytokine concentrations in DR patients before injection therapy were ana-lyzed.Results Compared to before injection therapy,the concentrations of VEGF-A,PLGF,and IL-23 in the aqueous humor of patients in the DME group decreased significantly after treatment(all P＜0.05);additionally,the CMT de-creased,and the BCVA increased(both P＜0.05).After injection therapy,the concentrations of VEGF,PLGF,IL-1β,IL-23,IL-17A,and TNF-α in the aqueous humor of patients in the PDR group significantly decreased compared to before injec-tion therapy(all P＜0.05).Before injection therapy,the levels of VEGF-A,PLGF,and IL-23 in the aqueous humor of pa-tients in the DME group were higher than those in the PDR group,and the differences were statistically significant(all P＜0.05).The correlation analysis results showed that before injection therapy,VEGF was negatively correlated with BCVA(r=-0.767,P=0.004)and was positively correlated with CMT(r=0.662,P=0.019)and IL-23(r=0.765,P=0.004)in the DME group.There was no correlation between the cytokines in the aqueous humor of patients in the PDR group be-fore injection therapy(all P＞0.05).Conclusion Changes in the concentration of VEGF-A,PLGF,and IL-23 are closely related to the occurrence and development of DR.Anti-VEGF treatment can improve BCVA and decrease CMT in DME pa-tients.The expression level of IL-23 in aqueous humor can serve as a predictive factor for the anti-VEGF efficacy in DR pa-tients,providing new targets for early diagnosis and treatment of DR.