Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.

Objective:To observe the intervention effect of personalized nutrition program combined with rehabilitation training in stroke rehabilitation patients.Methods:86 stroke rehabilitation patients who were admitted to our hospital from January 2023 to June 2024 were prospectively selected,they were divided into control group and study group according to the random number table method,with 43 cases in each group,the control group received rehabilitation training,while the study group received personalized nutrition program combine with rehabilitation training.Simple Fugl Meyer motor function(FMA)score,immune function indicators[immunoglobulin(Ig)A,IgG,complement C3,IgM,complement C4],National Institutes of Health Stroke Scale(NIHSS),nutritional status indicators[albumin(ALB),prealbumin(PA),total protein(TP),hemoglobin(HB)],Stroke Specific Quality of Life Scale(SS-QOL),Barthel Index(BI)score were compared between the two groups.Results:NIHSS score in the study group at 8 weeks after intervention was lower than that in the control group,and SS-QOL score,BI score,FMA score,IgM,IgA,IgG,complement C3,complement C4,ALB,HB,TP and PA were higher than those in the control group(P＜0.05).Conclusion:Personalized nutrition program combined with rehabilitation training in stroke rehabilitation patients,can reduce neurological damage,improve limb motor function,enhance nutritional status,immunity,and quality of life.

Objective To explore the potential causal relationship between childhood obesity and the risk of inflammatory bowel disease(IBD)based on Mendel randomization(MR).Methods The genome-wide association study(GWAS)data for childhood obesity included 5 530 cases and 8 318 controls.The GWAS data for IBD included 5 673 cases and 213 119 controls.The GWAS data for ulcerative colitis included 4 320 cases and 210 300 controls.The GWAS data of Crohn's disease included 2 056 cases and 210 300 controls.The risk association between obesity and the occurrence of IBD was analyzed using the inverse variance weighted meth-od(IVW),general model,weighted model,weighted median,and MR-Egger.Results Fourteen independent single nucleotide polymorphisms(SNP)significantly associated with childhood obesity were screened out as instrumental variables.IVW analysis results showed that no potential causal association was found between childhood obesity and IBD(OR=1.048,95%CI:0.976-1.125),ulcerative colitis(OR=1.026,95%CI:0.946-1.113),and Crohn's disease(OR=1.123,95%CI:0.993-1.269,P>0.05).Conclusion There was no causal relationship between childhood obesity and the risk of IBD.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective:To retrospectively analyze the changes in the proportion of refined lymphocyte subsets in peripheral blood of patients with Graves disease (GD), and their correlation with the clinical characteristics and efficacy of GD, and to explore the immunological pathogenesis of Graves disease for seeking new therapeutic targets.Methods:A total of 97 newly diagnosed GD patients (GD group), 27 patients after treatment (treatment group), and 31 healthy individuals (control group) who visited the Fifth Medical Center of the PLA General Hospital from 2018 to 2021 were included in this study. The data of refined lymphocyte subsets, thyroid function, blood routine and clinical treatment of the three groups were compared and analyzed. The t-test and rank sum test were used to compare the proportions of lymphocyte subsets among different groups, and Pearson correlation analysis was used to analyze the correlation between the proportions of lymphocyte subsets and thyroid function indicators.Results:The proportion of B cells in GD group was higher than that in the control group [16.2%(11.8%, 21.8%) vs 10.2%(8.1%,13.6%)], while the proportion of natural killer (NK) cells was lower [9.4%(4.9%, 13.6%) vs 14.6%(12.1%,18.8%)], and the differences were statistically significant ( P<0.05). Abnormal T cell differentiation: the proportions of functional cells, including activated T cells, memory T cells, clustering antigen(CD)4+memory T cells, Th1 cells, and Tc1 cells, were lower than that in the control group [3.2%(2.1%, 5.7%) vs 5.8%(3.0%, 9.3%), P<0.05; 36.7% (29.9%, 48.1%) vs 48.0%(39.2%,57.7%), P<0.05; 23.1%(17.4%, 30.1%) vs 28.9%(23.3%,34.6%), P<0.05; 16.4% (11.8%, 23.6%) vs 24.3%(16.9%,28.5%), P<0.05; 28.5% (14.7%, 39.2%) vs 46.3%(21.6%,69.2%), P<0.05]. The proportion of activated T cells in the treatment group was higher than that in the GD group [6.5% (4.6%, 13.6%) vs 3.2% (2.1%, 5.7%), P<0.05]. The total triiodothyronine results showed positive correlations with B cells ( r=0.356, P<0.01) and negative correlations with NK cells ( r=?0.416, P<0.01), while the total thyroxine values showed negative correlations with NK cells and activated T cells ( r=?0.318,?0.335; P<0.01). Thyroid stimulating hormone and CD8+initial T cells were positively correlated ( r=0.382, P<0.01). The proportion of B cells, cytotoxic T cells and suppressor T cells in CD8+cells of patients with complications [such as Graves orbitopathy (GO), thyroid toxic cardiomyopathy, etc.] was significantly different from that of the simple GD patients [18.3% (14.1%, 27.1%) vs 14.6% (10.8%, 21.4%), Z=2.54, P<0.05; 73.4%(65.6%,83.6%)vs 65.0%(50.3%,79.3%), Z=2.93, P<0.05; 26.6%(16.4%, 37.5%)vs 35.0%(20.7%,49.7%), Z=?2.74, P<0.05]. The proportion of suppressor T cells in GO patients was lower than that in non-GO patients [6.1% (3.4%, 8.1%) vs 8.5% (4.9%, 13.6%), Z=?3.20 P<0.05]. Conclusion:There are significant alterations in the circulating immune cells of GD patients, suggesting that immunological abnormalities play a crucial role in the onset and progression of the disease.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.

Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*

Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Quality Control ; Humans ; Animals