Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Objective: To construct and validate a prognosis model related to ferroptosis in urinary tract tumors using bioinformatics methods. Methods: RNA-seq and clinical data from TCGA′s BLCA and KIRC datasets were analyzed to establish the prognostic model, and then were validated using ICGC and GEO data. Prognostic genes associated with ferroptosis were identified through univariate Cox, LASSO-Cox, and multivariate Cox regression analyses. Co-expression and protein-protein interaction(PPI) network analyses determined the relationships among these genes. Immune infiltration analysis explored the association between ferroptosis-related prognostic genes and the immune microenvironment. Functional enrichment analysis of differentially expressed genes between high and low-risk groups in BLCA and KIRC prognostic models was conducted to investigate potential mechanisms by which ferroptosis-related genes regulate BLCA and KIRC prognosis. Results: Significant prognostic gene signatures associated with ferroptosis were identified in BLCA and KIRC. For BLCA, the genes EGR1, ZEB1, P4HB, WWTR1, JUN, CDO1,SCD,SREBF1,CAV1, and GALNT14 were significant. For KIRC, the genes ASMTL-AS1, CHAC1,MT1G, RRM2, TIMP1, DPEP1, GLRX5, and NDRG1 were significant. Ferroptosis-related miRNAs linked to the prognosis of both cancers were also identified. The constructed risk models based on these genes and miRNAs predicted patient prognosis in TCGA-BLCA and KIRC, with low-risk groups showing significantly higher overall survival(P<0.05). The hazard ratios for these models ranged from 2.54(95%CI: 1.73-3.74) to 4.74(95%CI: 3.47-6.47), with AUC values above 0.60. Co-expression analysis and PPI networks revealed high correlation levels between JUN and EGR1 in BLAC and between SCD and SREBF1. Immune infiltration analysis indicated positive correlations between EGR1, CAV1, JUN, and immune scores, while SREBF1 showed a negative correlation. Conclusion The prognosis model based on ferroptosis-related genes effectively predicts patient outcomes in BLCA and KIRC. This model can serve as a reference for targeting ferroptosis to assess the prognosis of BLCA and KIRC patients.

Objective:To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in cases of febrile respiratory syndrome in China from 2010 to 2020.Methods:Based on the sub-project of the National Science and Technology Major Project for Infectious Disease Prevention and Control "Infectious Disease Monitoring Technology Platform", active monitoring of febrile respiratory syndrome cases was conducted in sentinel hospitals in 31 provinces across China (excluding Hong Kong, Macau, and Chinese Taiwan) from January 2010 to December 2020, resulting in the inclusion of 191 441 cases. Clinical specimens of monitored cases were screened for HRSV nucleic acid, and the differences in HRSV detection rates among different age groups, regions, and time periods were analyzed using the χ 2 test/Fisher exact probability method. Results:Among the 191 441 cases of febrile respiratory syndrome in China from 2010 to 2020, the age group M ( Q1, Q3) was 9 (2, 40) years old, with 83 773 cases (43.8%) in the <5 years old group. There were 113 660 males, with a male-to-female ratio of 1.5∶1.0. There were as many as 105 508 cases (55.2%) of scattered children and preschool children. About 70 565 cases (36.9%) lived in the northern region. There were 13 858 HRSV positive cases, with a total positive rate of 7.2%. The positive rate of HRSV detection in the northern population was 5.7% (4 004/70 565), which was lower than that in the southern population (8.2%, 9 854/120 876), and the difference was statistically significant (χ 2=407.4, P<0.001). HRSV was detected in all age groups, with the highest positive rate of 23.9% in the <6 months age group. The month with the highest positive rate was December, and autumn and winter were the main epidemic seasons. Both northern and southern HRSV subtypes were mainly infected with type A, with a low proportion of mixed infections of type A and type B. Conclusion:HRSV is a common pathogen causing respiratory infections in children from 2010 to 2020. It can be detected throughout the year and shows the main peak of prevalence in autumn and winter. The HRSV strain is mainly classified as a type A infection.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective:To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in cases of febrile respiratory syndrome in China from 2010 to 2020.Methods:Based on the sub-project of the National Science and Technology Major Project for Infectious Disease Prevention and Control "Infectious Disease Monitoring Technology Platform", active monitoring of febrile respiratory syndrome cases was conducted in sentinel hospitals in 31 provinces across China (excluding Hong Kong, Macau, and Chinese Taiwan) from January 2010 to December 2020, resulting in the inclusion of 191 441 cases. Clinical specimens of monitored cases were screened for HRSV nucleic acid, and the differences in HRSV detection rates among different age groups, regions, and time periods were analyzed using the χ 2 test/Fisher exact probability method. Results:Among the 191 441 cases of febrile respiratory syndrome in China from 2010 to 2020, the age group M ( Q1, Q3) was 9 (2, 40) years old, with 83 773 cases (43.8%) in the <5 years old group. There were 113 660 males, with a male-to-female ratio of 1.5∶1.0. There were as many as 105 508 cases (55.2%) of scattered children and preschool children. About 70 565 cases (36.9%) lived in the northern region. There were 13 858 HRSV positive cases, with a total positive rate of 7.2%. The positive rate of HRSV detection in the northern population was 5.7% (4 004/70 565), which was lower than that in the southern population (8.2%, 9 854/120 876), and the difference was statistically significant (χ 2=407.4, P<0.001). HRSV was detected in all age groups, with the highest positive rate of 23.9% in the <6 months age group. The month with the highest positive rate was December, and autumn and winter were the main epidemic seasons. Both northern and southern HRSV subtypes were mainly infected with type A, with a low proportion of mixed infections of type A and type B. Conclusion:HRSV is a common pathogen causing respiratory infections in children from 2010 to 2020. It can be detected throughout the year and shows the main peak of prevalence in autumn and winter. The HRSV strain is mainly classified as a type A infection.

Objective:To investigate the impact of age,various hormonal levels,and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction(ED).Me-thods:A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography(CDDU)and intracavernosal injection test(ICI)at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023.Data were managed and processed using SPSS 29.0,and a multivariable Logistic regression analysis was conducted.Results:A total of 700 ED patients were included,with 380 showing negative ICI results and 320 positive.In the study,84 patients had a peak systolic velocity(PSV)＜25 cm/s,while 616 had PSV ≥ 25 cm/s;202 patients had end-diastolic velocity(EDV)＞5 cm/s,and 498 had EDV ≤5 cm/s.264 patients had ab-normal PSV and/or EDV results,and 436 had normal results for both.Patients with vascular ED had sig-nificantly lower estrogen levels(t=-3.546,P＜0.001),lower testosterone levels(t=-2.089,P=0.037),and a higher rate of hyperglycemia(x2=12.772,P=0.002)compared with those with non-vascular ED.The patients with arterial ED were older(t=3.953,P＜0.001),had a higher rate of hyperglycemia(x2=9.518,P=0.009),and a higher estrogen/testosterone ratio(t=2.330,P=0.020)compared with those with non-arterial ED.The patients with mixed arteriovenous ED had higher age(t=3.567,P＜0.001),lower testosterone levels(t=-2.288,P=0.022),a higher rate of hyperglycemia(x2=12.877,P=0.002),and a larger estrogen/testosterone ratio(t=2.096,P=0.037)compared with those with normal findings.Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED(OR=1.009,95％CI:1.004-1.014),and glucose 7.0 mmol/L was a risk factor(OR=0.381,95％CI:0.219-0.661).Older age was a risk factor for arte-rial ED(OR=0.960,95％CI:0.938-0.982).Additionally,older age(OR=0.976,95％CI:0.958-0.993)and glucose levels of 5.6-6.9 mmol/L(OR=0.591,95％CI:0.399-0.876)were also risk fac-tors for mixed arterio-venous ED.Conclusion:Hyperglycemia and aging may impair penile cavernous body vascular function,while higher levels of estrogen may have a protective effect on it.

Objective:To identify the predictive validity of C-reactive protein to albumin ratio (CAR) in the early diagnosis of Kawasaki disease shock syndrome (KDSS).Methods:This was a retrospective case-control study.Children with KDSS hospitalized in the Children′s Hospital, Capital Institute of Pediatrics, from January 2019 to December 2022, were selected as the case group, and children with Kawasaki disease (KD) hospitalized in the same period were selected as the control group.After a 1︰4 propensity score matching (PSM) of age and gender, the demographic characteristics, laboratory and imaging examinations, and other clinical data of all the patients were analyzed and compared between the two groups.Multivariate Logistic regression was used to analyze the possible risk factors of KDSS.The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of risk factors for KDSS.Results:There were 45 KDSS children and 269 KD children included in the study.The KDSS patients were older than the KD patients at the onset [43(19, 51) months vs.24(14, 44) months, Z=2.791, P<0.05].After age- and gender-based PSM, there were 45 children in the KDSS group and 180 children in the KD group.The children with KDSS had a shorter duration of fever [6(4, 6) days vs.6(5, 7) days] and a higher risk of coronary artery lesions [42.22%(19/45) vs.25.56%(46/180)] compared to those with KD ( Z=2.184, χ2=4.868, all P<0.05).Multivariate Logistic regression analysis showed that CAR, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, D-dimer, platelet count, serum sodium and estimated glomerular filtration rate were the independent risk factors for KDSS.The area under the ROC curve for identifying KDSS based on CAR was 0.850.When the cutoff value of CAR was 2.73, the sensitivity and specificity were 77.80% and 81.67%, respectively.After subgroup analysis, each one-unit increment in CAR was associated with a 239.6% increased risk of KDSS in children ≥ 3 years old ( OR=3.396, 95% CI: 2.105-5.479, P<0.05). Conclusions:As one of the independent risk factors for KDSS, CAR has high predictive value for early diagnosis of KDSS.In KD patients ≥ 3 years old, the risk of developing KDSS increases significantly with increased CAR.

【Objective】 To investigate the current status of incision sites to obtain intact specimens in laparoscopic nephrectomy by urologists in China, so as to provide reference for the standardized procedure. 【Methods】 During Jun.20, 2021 and Jul.4, 2021, more than 20 000 urologists in a WeChat group were surveyed with a questionnaire. The general data, incision sites and related complications were statistically analyzed. 【Results】 A total of 601 valid questionnaires were collected, covering urologists from 31 provinces, autonomous regions and municipalities. Surgical approaches: 68 urologists chose trans-abdominal approach, 432 chose posterior abdominal space approach, 101 chose both surgical approaches. Incision sites: 97 urologists chose lumbar transverse incision, 202 chose dorsal oblique incision of the waist, 119 chose ventral oblique incision, 93 chose the paramedian incision, 112 chose the lower abdominal oblique incision (Gibson), 11 chose the transverse lower abdominal incision (Pfannenstiel), 7 chose the median incision of the lower abdomen, 2 chose the median incision in the upper abdomen, 15 chose axillary midline direct incision; 399 chose to cut off the muscles, and 202 chose not to. Complications: 232 urologists reported pain after 2 weeks, 369 reported no pain; 325 reported numbness after 2 weeks, 276 reported no numbness; 66 reported incisional hernia, 535 reported no hernia. 【Conclusions】 Chinese urologists tend to choose retroperitoneoscopic nephrectomy and waist incision to obtain intact specimens. Transperitoneal laparoscopic nephrectomy has a variety of incisions for intact specimens. There is no standardized incision sites to obtain intact specimens.

Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti-tumor agent. However, its anti-tumor mechanism against hepatocellular carcinoma is unknown. This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action. We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy. Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways. Subsequently, using specific inhibitors, we found that apoptosis and autophagy had mutually reinforcing effects. In addition, further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like (BNIP3L) levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors. Overall, our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways. Therefore, PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.
Humans ; Mitophagy ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Cell Line ; Autophagy ; Apoptosis ; Membrane Proteins ; Proto-Oncogene Proteins/genetics* ; Tumor Suppressor Proteins/pharmacology*