OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

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Objective To investigate the value of repeat renal biopsy in the treatment and prognosis of nephrotic syndrome(NS)and acute kidney injury(AKI)following immunosuppressive therapy in patients with lupus nephritis(LN). Methods A retrospective analysis was conducted for the clinicopathological data and follow-up records of LN patients undergoing repeat renal biopsy at Peking Union Medical College Hospital from January 1,2009 to December 31,2021. Results A total of 76 patients(55 females,72.4%)were included in this study,with the mean age at the first biopsy being(29.0±10.4)years,the median inter-biopsy interval of 4.0(2.0,7.0) years,and the median total follow-up duration of 7.5(5.0,13.8)years.Pathological transformation occurred in 46(60.5%)patients,and 2 patients had comorbid diabetic nephropathy.At repeat renal biopsy,50(65.8%) patients presented NS.These patients demonstrated lower estimated glomerular filtration rate(eGFR)(P<0.001),higher chronicity index(CI)(P=0.029),and higher complement C3(P<0.001)and C4(P<0.001)levels than those with NS at the first renal biopsy(n=50).Among the 28(36.8%) patients with AKI at repeat renal biopsy,8(28.6%)experienced acute exacerbation of chronic renal insufficiency.These patients exhibited higher serum creatinine level(P=0.002),C4 level(P=0.033),CI(P=0.042),and prevalence of thrombotic microangiopathy(P=0.046)than the patients showing AKI at the first renal biopsy(n=16),while the activity index(AI)showed no significant difference(P=0.051).Over 50% of NS and AKI patients underwent treatment modifications post-repeat renal biopsy,with clinical remission rates comparable to those after the first renal biopsy(both P>0.05).Elevated CI(≥5,P=0.001)and serum creatinine(≥140 μmol/L,P<0.001)at repeat renal biopsy were identified as independent risk factors for poor prognosis.The patients with AKI at repeat renal biopsy had higher incidence of endpoint events than the non-AKI patients(P=0.015).Neither AKI at the first renal biopsy nor NS at both biopsies had significant associations with prognosis. Conclusions Repeat renal biopsy reveals not only sustained high disease activity but also accelerates chronic progression in LN patients,which underscore its critical role in guiding the therapy for severe LN post-immunosuppression.AKI,CI≥5,and serum creatinine ≥140 μmol/L at repeat renal biopsy are strongly associated with poor prognosis.
Humans ; Lupus Nephritis/drug therapy* ; Female ; Retrospective Studies ; Adult ; Male ; Prognosis ; Biopsy ; Kidney/pathology* ; Acute Kidney Injury/pathology* ; Nephrotic Syndrome/pathology* ; Glomerular Filtration Rate ; Young Adult ; Immunosuppressive Agents/therapeutic use* ; Middle Aged

The study aims to investigate and compare the effects of probiotics and docosahexaenoic acid (DHA) with the Alzheimer's disease (AD) therapeutic drug donepezil on the learning cognition and brain damage related indexes in AD mice, and to provide experimental basis for its treatment of AD. All animal experiments were approved by the Ethics Committee of the Henan University of Chinese Medicine (ethics number DWLL2018080003). Fifty male C57BL/6J mice were randomly assigned to one of five groups: sham-operated, model, donepezil (10 mg·kg^-1), probiotic (2.7×10⁹ CFU·d^-1), and DHA (0.104 g·kg^-1). Except for the sham-operated group, the AD animal model was established by injecting Aβ_25-35 (200 μmol·L^-1) in the lateral ventricle, followed by gavage administration for 4 weeks. In all mouse groups, learning memory ability, neuronal morphology in the hippocampus, apoptosis of primary hippocampal cells, and immune cell levels were detected. The levels of Aβ_1-42, Aβ_1-40, p-Tau, AchE, Ach, oxidative stress, glial cell activation, and the inflammatory factors IL-1β, IL-10, and TNF-α in the brain tissue of mice were also detected. 16S rDNA sequencing was used to further investigate the effects of donepezil and probiotics on AD. Donepezil, probiotics and DHA improved cognitive deficits and enhanced learning memory in Aβ_25-35-induced mice by increasing locomotion time, locomotion distance, autonomic alternation rate, and shortening the time to reach the plateau; it significantly attenuated Aβ_25-35-induced brain injury and neuroinflammation in mice by decreasing Aβ_1-42, Aβ_1-40, p-Tau, AchE, IL-1β, TNF-α, and MDA and increasing the levels of Ach, IL-10, GSH-Px, and T-SOD in brain tissues, as well as decreasing the activation of glial cells, and had a modulatory effect on immune cells. 16S rDNA sequencing shows that both donepezil and probiotics restore flora homeostasis and that differential bacteria are strongly associated with cognition, AD pathology, and neuroinflammation. Combining all indicators, donepezil and probiotics were more effective than DHA. All in all, donepezil, probiotics and DHA ameliorate Aβ_25-35-induced cognitive dysfunction and brain damage in mice by modulating immune cells, reducing the number of apoptotic cells and glial cell activation in the brain, and decreasing the levels of oxidative stress and inflammatory factor expression, among which the effects of donepezil and probiotics were better than those of DHA, and the therapeutic effects of donepezil and probiotics on AD were closely related to the modulation of gut microbiome.

Objective To explore the expression of miR-30d-5p in cervical cancer and its effect on malignant biological behavior of cervical cancer cells.Methods qRT-PCR was used to detect the expression of miR-30d-5p in cervical cancer tissues,adjacent tissues,normal cervical cells and cervical cancer cells.The mimic negative control(mimic NC)and miR-30d-5p mimic were transfected into SiHa cells,and the transfection efficiency of miR-30d-5p was detected by qRT-PCR.CCK-8 and cell clone formation experiments were used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.Scratch wound healing assay and Transwell assay were used to detect cell migration and invasion,respectively.Western blot was used to detect the expression of cell apoptosis and invasion-related proteins.Results Compared with adjacent tissues,the expression level of miR-30d-5p in cervical cancer tissues was significantly down-regulated(P<0.01).Compared withEct1/E6E7 cells,the expression level of miR-30d-5p in cervical cancer cell lines was significantly decreased(P<0.01).Overexpression of miR-30d-5p inhibited the proliferation,migration and invasion of SiHa cells and promoted apoptosis(P<0.01).In addition,overexpression of miR-30d-5p significantly down-regulated the expression levels of Bcl-2,N-cadherin and Vimentin(P<0.01),and significantly up-regulated the expression levels of Bax,cleaved caspase-3 and E-cadherin(P<0.01).Conclusion miR-30d-5p is significantly down-regulated in human cervical cancer tissues and related cervical cancer cell lines.miR-30d-5p can inhibit cervical cancer cells in vitro by inhibiting cell proliferation,migration and invasion,suggesting that miR-30d-5p may be a potential new target for diagnosis and treatment of cervical cancer patients.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To compare the postoperative recurrence rates between Thulium laser en bloc resection of bladder tumor (ERBT) and traditional transurethral resection of bladder tumor (TURBT) in treating patients with non-muscle invasive bladder cancer (NMIBC).Methods:A retrospective analysis was conducted on the clinical data of 1 439 patients with NMIBC who underwent either Thulium laser ERBT or TURBT in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between January 2010 and March 2024. Among them, 201 patients received Thulium laser ERBT, while 1 238 patients underwent TURBT. Propensity score matching (PSM) was employed in a 1∶1 ratio to eliminate selection bias due to non-random assignment, ensuring the comparability of clinical baseline data such as gender, age, pathological diagnosis, T stage, tumor grade, tumor size, and tumor number between the two groups. Kaplan-Meier method was used to generate recurrence-free survival curves for the matched groups, and the log-rank test was conducted to compare differences between the groups. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting postoperative recurrence.Results:After PSM matching, 193 patients were included in each group. There were no statistically significant differences between the two groups in terms of gender ( P=0.317), age ( P=0.207), pathological type ( P=0.756), T stage ( P=0.402), tumor grade ( P=0.965), tumor size ( P=0.821), or number of tumors ( P=0.421). The median follow-up time was 16.2(8.0, 33.9) months. Excluding patients with non-urothelial tumors such as adenocarcinoma and squamous cell carcinoma, there were 180 cases in the Thulium laser ERBT group and 184 cases in the TURBT group. Survival analysis showed that the postoperative recurrence rate of urothelial carcinoma patients in the Thulium laser ERBT group was lower than that in the TURBT group [20.0%(36/180) vs. 38.6%(71/184), P<0.001]. Stratified survival analysis indicated that in patients with tumor diameters ≤30 mm [22.3%(29/130) vs. 33.6%(45/134), P=0.017] or >30 mm [14.0%(7/50) vs. 52.0%(26/50), P=0.002], the Thulium laser ERBT group had lower postoperative recurrence rate compared to the TURBT group.Among patients with single tumor, the recurrence rate in the Thulium laser ERBT group was lower than in the TURBT group[10.5%(11/105) vs. 31.5%(35/111), P<0.001]. However, among patients with multiple tumors, there was no statistically significant difference in recurrence rates between the Thulium laser ERBT group and the TURBT group [35.7%(25/70) vs. 47.9%(34/71), P=0.061]. Univariate and multivariate Cox regression analyses indicated that Thulium laser ERBT treatment was an independent protective factor against postoperative recurrence in NMIBC patients ( HR=0.44, 95% CI 0.30-0.66, P<0.001). Patients with adenocarcinoma ( HR=5.85, 95% CI 2.07-16.51, P<0.001), squamous cell carcinoma ( HR=2.98, 95% CI 1.04-8.55, P=0.042), or other types of tumors ( HR=2.98, 95% CI 1.14-7.75, P=0.026) had higher risks of recurrence. High-grade tumor patients faced increased risks of postoperative recurrence ( HR=1.84, 95% CI 1.21-2.79, P=0.004). Additionally, tumors >30 mm had increased risks of postoperative recurrence compared to those ≤30 mm ( HR=2.00, 95% CI1.31-3.05, P=0.001). Patients with single tumor had significantly reduced risks of postoperative recurrence compared to those with multiple tumors ( HR=0.50, 95% CI 0.34-0.73, P<0.001). Conclusions:Regardless of tumor diameter (≤30 mm or >30 mm), Thulium laser ERBT significantly reduces the postoperative recurrence rate in patients with urothelial carcinoma compared to TURBT, with the advantage being more pronounced in patients with single bladder tumor. Additionally, patients with high-grade tumors, tumor diameters >30 mm, or multiple bladder tumors have higher risk of postoperative recurrence.

A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient′s nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 μmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5?147 μmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 μmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.