Aim To investigate the effect of Dahuang Tangluo pills(DHTL)on NOD-like receptor protein 3(NLRP3)/cysteine aspartate proteolytic enzyme-1(caspase-1)/apodermic D(GSDMD)pathway-media-ted pyroptosis in db/db mice with diabetic kidney dis-ease(DKD)and the underlying mechanism.Methods Eight db/m mice were selected as control group,and forty db/db mice were randomly divided into mod-el group,low dose group,medium dose group,high dose group and dapagliflozin group,with eight mice in each group.The control group and model group were given equal volume normal saline intragastric adminis-tration,the low,medium and high dose groups were given DHTL solution of 0.9,1.8 and 3.6 mg·kg-1,respectively,and the dapagliflozin group was given dapagliflozin tablet solution of 1.5 mg·kg-1,and the six groups were given intragastric administration once a day for 10 weeks.The body weight of mice was meas-ured daily and the dose was adjusted during adminis-tration.Fasting blood glucose(FBG)and body weight were measured after administration.The levels of 24-hour urinary total protein(24h-UTP),blood creatinine(Scr)and urea nitrogen(BUN)were measured by au-tomatic biochemical analyzer.The levels of interleukin-1 β(IL-1β),interleukin-6(IL-6),interleukin-18(IL-18)and tumor necrosis factor-α(TNF-α)in re-nal tissue of mice were determined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of renal tissue were observed by hematoxylin-eosin(HE)staining.The DNA damage in mouse kid-ney tissue was observed using in situ end labeling(TUNEL)staining.The mRNA and protein expres-sions of NLRP3,caspase-1 and GSDMD in mouse kid-ney tissues were detected by Real-time quantitative PCR and Western blot.Results Compared with the control group,FBG,body weight,IL-1β,IL-6,IL-18 and TNF-α in the model group significantly increased(P＜0.01).The mRNA and protein expressions of NLRP3,caspase-1 and GSDMD in mouse kidney tis-sues significantly increased(P＜0.01).Compared with the model group,the levels of FBG,body weight,IL-1β,IL-6,IL-18 and TNF-α in each administration group significantly decreased(P＜0.05).The patho-logical morphology of renal tissue was improved in dif-ferent degrees,and the number of positive cells in re-nal tissue was significantly reduced(P＜0.05).The mRNA and protein expressions of NLRP3,caspase-1 and GSDMD in renal tissue of mice in high and medi-um dose of DHTL and dapagliflozin group significantly decreased(P＜0.05).Conclusions DHTL can im-prove the renal injury of DKD,and its mechanism may be through the regulation of NLRP3/caspase-1/GSD-MD pathway to inhibit pyroptosis and relieve the in-flammatory response of DKD mice.

Complete androgen insensitivity syndrome(CAIS) is characterized by lack of androgen response in target organs due to androgen receptor dysfunction, resulting in feminized external genitalia. Individuals with CAIS are typically advised to live as females. This article reports a patient diagnosed with CAIS and gender dysphoria in adulthood. Following the removal of a left pelvic mass, pathology indicated cryptorchidism with a concurrent Leydig cell tumor. Genetic testing revealed a deletion mutation in exon 3 of androgen receptor gene. During follow-up, the patient underwent gender reassignment, transitioning socially from female to male. This case provides new insights into gender allocation for CAIS patients.

The laboratory physicians are high-level laboratory medicine talents who are in short supply in China at present. They should possess solid clinical and laboratory knowledge, skilled clinical laboratory techniques, clinical and laboratory analyzing ability, and good communicating skills. In our country, the resident training system for laboratory physicians has been basically established, but there is still room for improvement in the implementation of the training. In order to adapt to the needs of the new situation, focusing on the purpose of training and guided by the rules of standardized residency training, the clinical laboratory training base has kept exploring and practicing integrated teaching based on organ system in standardized residency training of clinical laboratory. Through the exploring and practicing, the clinical laboratory training base has tried to fulfill the integration of clinical disease diagnosis and treatment and laboratory analysis, to gradually establish a distinctive training and teaching model for laboratory physicians, and to train laboratory physicians to get competent to the work with initial ability. Meanwhile, the clinical laboratory training base has explored characterized experience for the training of master′s degree of clinical laboratory diagnostics in"Laboratory physician training experimental class".

Objective To explore the influencing factors of mild cognitive impairment(MCI)in patients with atrial fibrillation and diabetes mellitus,and to establish the prediction model,so as to provide guidance for the treatment of MCI in patients with atrial fibrillation and diabetes mellitus.Methods 199 patients with atrial fibrillation and diabetes diagnosed in the second ward of Cardiovascular Department of the Fifth Affiliated Hospital of Zhengzhou University from January 2023 to January 2024 were analyzed.The related factors of MCI in patients with atrial fibrillation and diabetes mellitus were analyzed by univariate analysis and multivariate logistic regres-sion.According to the results of multivariate logistic regression analysis,the prediction model of MCI in patients with atrial fibrillation and diabetes mellitus was established.Results Univariate analysis showed that age(P=0.002 3),homocysteine(P＜0.000 1),fasting blood glucose(P=0.022 5),glycated hemoglobin(P=0.006 6),and blood uric acid(P=0.032 2)were the influencing factors of MCI.Multivariate logistic regression analysis:age(OR=1.08,P=0.000 4),homocysteine(OR=1.37,P＜0.000 1),fasting blood glucose(OR=1.22,P=0.023 5),glycated hemoglobin(OR=1.61,P=0.004 2),and blood uric acid(OR=1.29,P=0.009 1)were the independent influencing factors of MCI.The optimal threshold is when the Youden index(YI=sensitivity+speci-ficity)is maximum.At the optimal threshold,the sensitivity was 0.74,the specificity was 0.80,and the area under the curve(AUC)was 0.809,indicating that the model can effectively predict the occurrence of MCI.Conclusion Age,fasting blood glucose,blood homocysteine,blood uric acid and glycosylated hemoglobin are independent risk factors for MCI in patients with atrial fibrillation and diabetes.The clinical prediction model based on multivariate logistic regression has a certain predictive value for the occurrence of MCI in patients with atrial fibrillation and diabetes mellitus.

Objective To explore the inhibitory effect of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung cancer mice and its mechanism based on the lncRNA H19/miR-19b3p/FTH1 axis.Methods Totally 60 SPF grade male C57BL/6 mice were randomly selected as blank group,and Lewis lung cancer mouse model was replicated in the remaining 50 mice.The modeled mice were randomly divided into model group,cisplatin group,and TCM low-,medium-and high-dosage combined with cisplatin group,with 10 mice in each group.The cisplatin group was given intraperitoneal injection of cisplatin 5 mg/kg,while the TCM low-,medium-and high-dosage combined with cisplatin group were given Guiqi Yiyuan Ointment 1.75,3.5,7.0 g/kg by gavage combined with intraperitoneal injection of cisplatin 5 mg/kg,the blank group and model group were given equal volume of normal saline by gavage for 14 consecutive days.The general condition of mice was observed,the tumor mass of mice was measured,and the tumor inhibition rate,spleen index,and thymus index were calculated,HE staining was used to observe the pathological changes of tumor tissue,and the contents of malondialdehyde(MDA),reduced glutathione(GSH),hydrogen peroxide(H2O2),and ferrous ions(Fe2+)were detected in the tumor tissue,immunohistochemistry and Western blot were used to detect the expression of nuclear factor E2 related factor 2(Nrf2),glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and solute carrier family 7 member 11(SLC7A11)protein in tumor tissue,real time fluorescence quantitative PCR was used to detect the expression of lncRNA H19 and miR-19b3p mRNA in tumor tissue.Results Compared with the blank group,the body mass,spleen index and thymus index of mice in the model group were decreased(P<0.05).Compared with the model group,the mental state and tumor histopathological morphology of mice in each administration group were improved to different degrees,the tumor mass of mice was reduced(P<0.05),the spleen index and the thymus index of mice increased(P<0.05),tumor cell lysis,rupture,and decrease in quantity,the contents of MDA,H2O2,Fe2+in tumor tissue increased(P<0.05),while GSH content decreased(P<0.05),the expression of Nrf2,GPX4,FTH1,SLC7A11 protein in tumor tissue decreased(P<0.05),the lncRNA H19 mRNA expression decreased(P<0.05),miR-19b3p mRNA expression increased(P<0.05).Compared with the cisplatin group,the tumor mass of mice in TCM high-dosage combined with cisplatin group reduced(P<0.05),the body mass,spleen index and thymus index increased(P<0.05),the contents of MDA,H2O2,Fe2+in tumor tissue of mice increased(P<0.05),the content of GSH decreased(P<0.05),the expression of Nrf2,FTH1,SLC7A11,GPX4 protein expression decreased(P<0.05),lncRNA H19 mRNA expression decreased(P<0.05),miR-19b3p mRNA expression increased(P<0.05).Conclusion Guiqi Yiyuan Ointment combined with cisplatin can significantly inhibit the tumor of Lewis lung cancer mice,and its mechanism may be related to regulating the expression of ferroptosis molecules related to the lncRNA H19/miR-19b3p/FTH1 axis.

Objective:To explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in different regions of the kidney in distinguishing IgA nephropathy (IgAN) patients from healthy volunteers.Methods:This study was a cross-sectional study. Eighty-four patients diagnosed with IgAN (IgAN group) who underwent renal biopsy (lower pole of the left kidney) and were pathologically confirmed at the First Medical Center of PLA General Hospital from February 2022 to September 2023 and thirty-four healthy volunteers (control group) were included prospectively. The regions of interest were outlined in the right renal cortex, medulla, and parenchyma for all subjects, and the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D *), and perfusion fraction (f) were measured in the corresponding regions. The differences in IVIM-DWI parameters between the IgAN group and the control group were compared using the student′s t-test or the Mann-Whitney U test. Receiver operating characteristic curve analysis was performed on the parameters with statistically significant differences, and the area under the curve (AUC) was calculated. Results:There were statistically significant differences in renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values between the IgAN group and the control group ( Z=-3.03, -2.21, -2.62, -2.03, -2.03; P=0.002, 0.027, 0.009, 0.043, 0.042). The AUCs (95% CI) for diagnosing IgAN using renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values were 0.679 (0.586-0.762), 0.630 (0.537-0.717), 0.654 (0.535-0.774), 0.619 (0.497-0.742), and 0.620 (0.495-0.745), respectively. There were no statistically significant differences in renal medullary ADC, D, renal cortex, medulla and parenchyma D *, renal cortical and renal parenchymal f values between the two groups ( P>0.05). Conclusion:The quantitative parameters of renal IVIM-DWI are influenced by different measurement regions, among which the ADC, D of renal cortex and parenchyma, and f of renal medulla can be used for the initial diagnosis of IgAN.

OBJECTIVE To construct a double helix model for evaluating the job competency of licensed pharmacists in retail pharmacies， and to provide a reference for building a talented team of licensed pharmacists and promoting the high-quality development of pharmaceutical care. METHODS Based on the competency iceberg model and double helix structure theory， literature analysis and the Delphi method were adopted to explore the model indicators； questionnaires were designed to survey licensed pharmacists in retail pharmacies from Shandong Province. The exploratory factor analysis was used to correct the model indicators and establish a double helix model for evaluating the job competency of licensed pharmacists in retail pharmacies， which was examined by validation factor analysis. RESULTS The recovery rate of the questionnaires in the two rounds of expert consultation was greater than 90%， the expert authority coefficients were both more than 0.86， and the overall Kendall’s W values were 0.288 and 0.510， respectively； after the correction of the exploratory factor analysis， the double helix model for evaluating the job competency of licensed pharmacists in retail pharmacies was established， which contained 4 first-level indexes such as occupational literacy， occupational knowledge， occupational competency and internal motivation， and 23 second-level indexes. The model contained occupational knowledge and occupational competency in the explicit competency chain， occupational literacy and internal motivation in the implicit competency chain， and policy support， incentive mechanism， education and training as the hydrogen bonds connecting the two main chains. The validation factor analysis showed that the model’s goodness of fit index， comparative fit index， and normed fit index all exceeded 0.9； the reliability of the combination of the four first-level indexes ranged from 0.89 to 0.95； the average variance extracted ranged from 0.58 to 0.75， and Cronbach’s α coefficients for both the overall model and the first-level indicators were all greater than 0.84. CONCLUSIONS The constructed double helix model for evaluating the job competency of licensed pharmacists in retail pharmacies is scientific， reasonable and practical.

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 expression of PLCD3 mRNA in the synovium of osteoarthritis(OA)and its relationship with immune cell infiltration.Methods Based on the differentially expressed genes of OA found in the previous study,the expression of phospholipase Cδ3(PLCD3)mRNA was detected by col-lecting synovial samples from OA group and control group.CIBERSORT algorithm was used to analyze the infiltration pattern of immune cells in OA group and control group,and the correlation between PLCD3 and infiltrating immune cells was further analyzed.Results Compared with the control group,the relative expres-sion level of PLCD3 mRNA was significantly increased in synovial samples of OA group(P<0.05).The pro-portions of B cells naive,NK cells activated,M2 macrophages and mast cells activated in synovial tissues of OA group were relatively high(P<0.05).PLCD3 was positively correlated with the proportion of these four immune cells(P<0.05).Conclusion PLCD3 may be a key biomarker for the diagnosis of OA,which may be involved in the pathogenesis of OA by interacting with infiltrating immune cells.

BACKGROUND:Molecular mechanisms targeting the miRNA/mRNA axis to regulate osteoarthritis disease process have been studied.We identified the mRNA:phospholipase C delta 3(PLCD3)and its target miRNA(miR-34a-5p)with clinical predictive value through previous bioinformatics studies,while experiments to verify their specific roles and mechanisms in regulating osteoarthritis are still lacking. OBJECTIVE:To investigate the regulatory role and mechanism of miR-34a-5p/PLCD3 axis on osteoarthritis progression. METHODS:The synovium of 15 patients with knee osteoarthritis was selected as the osteoarthritis group,and the synovium of 15 young patients with internal fixation of patellar fracture caused by trauma during the same period was selected as the control group.The expression of PLCD3 and miR-34a-5p in the synovium was detected by real-time PCR.Human fibroblast like synovial cells-osteoarthritis(HFLS-OA)cells were treated by cell transfection and divided into miR-34a-5p mimic group,pCDH-PLCD3 group,miR-34a-5p mimic+pCDH-PLCD3 group,miR-34a-5p inhibitor group,si-PLCD3 group,and miR-34a-5p inhibitor+si-PLCD3 group.The relationship between PLCD3 and miR-34a-5p expression was detected by real-time PCR.The effects of HFLS-OA cell viability and cell migration in each group were detected by CCK-8 assay and cell scratch test.Western blot assay was used to detect the expression level of apoptosis marker protein.The expression of inflammatory factors was detected by ELISA. RESULTS AND CONCLUSION:(1)PLCD3 was a direct target of miR-34a-5p,and the expression levels of PLCD3 and miR-34a-5p were negatively correlated.(2)Upregulation of PLCD3 promoted proliferation of HFLS-OA cells and inhibited cell migration.The up-regulation of miR-34a-5p significantly inhibited the activity of HFLS-OA cells and enhanced cell migration.Overexpression of miR-34a-5p significantly increased the levels of Casp3 and Casp9 proteins in HFLS-OA cells,while overexpression of PLCD3 showed the opposite trend.(3)PLCD3 overexpression significantly increased the expression of interleukin 6 and tumor necrosis factor alpha in HFLS-OA cells,while miR-34a-5p mimics showed protective activity.(4)The miR-34a-5p/PLCD3 axis may affect the progression of osteoarthritis by regulating the inflammatory process or apoptosis of synovial cells.