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.

Purpose: Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis. Materials and Methods: Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic–clinical characteristics were analyzed. LC-WGS–based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted. Results: A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases. Conclusion CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

AIM To investigate the clinical effects of Cinobufosin Injection combined with RALOX-HAIC regimen on patients with hepatocellular carcinoma.METHODS Ninety-two patients were randomly assigned into control group(46 cases)for intervention of RALOX-HAIC regimen,and observation group(46 cases)for intervention of both Cinobufosin Injection and RALOX-HAIC regimen.The changes in short-term effects,survival situation,inflammatory indices(LCN2,NLRP3 inflammasome,NLR,PLR),immune indices(NK cells,CD8+T cells,IL-17,Th17/Treg)and incidence of toxic and side effects were detected.RESULTS Based on mRECIST,the observation group demonstrated higher disease control rate and objective remission rate than the control group(P＜0.05),along with lower disease progression(P＜0.05).After the treatment,the two groups displayed decreased inflammatory indices,IL-17,Th17/Treg(P＜0.05),and increased NK cells,CD8+T cells(P＜0.05),especially for the observation group(P＜0.05).The observation group exhibited lower incidence of abdominal pain,nausea,vomiting,diarrhea,leukopenia and thrombocytopenia than the control group(P＜0.05),and no significant differences in overall survival and incidence of other toxic and side effects were found between the two groups(P＞0.05).CONCLUSION For the patients with hepatocellular carcinoma,Cinobufosin Injection combined with RALOX-HAIC regimen can safely and effectively enhance body immune functions,and reduce in vivo immune indices.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective:To explore effect of Yishen Paidu Formula on inflammatory response in chronic renal failure(CRF)rats and role of Calcineurin/nuclear factor of activated T cell(NFAT).Methods:CRF rat model was constructed,and randomly grouped into model group,low,medium and high doses Yishen Paidu Formula groups,with 10 rats in each group,another 10 rats were fed normally as a blank group;general situation of rats was recorded;urine protein quantification kit was applied to detect 24-hour urine protein level of CRF rats in each group;serum creatinine and urea nitrogen levels of CRF rats were detected;ELISA was applied to detect serum IL-1β,IL-6 and TNF-α levels in CRF rats;pathological changes of renal tissue were observed by HE staining;Western blot was applied to detect expressions of fibroblast growth factor 23(FGF23),Klotho protein,Calcineurin,NFAT protein in renal tissue of CRF rats in each group.Results:Compared with blank group,levels of creatinine,urea nitrogen in serum,24 h urine protein in urine,IL-1β,IL-6,TNF-α in serum,and protein levels of FGF23,Calcineurin,NFAT in kidney tissue were obviously increased in model group,level of Klotho protein was obviously decreased(P<0.05).Compared with model group,levels of creatinine,urea nitrogen in serum,24 h urine protein in urine,IL-1β,IL-6,TNF-α in serum,and protein levels of FGF23,Calcineurin,NFAT in kidney tissue were obviously decreased in low,medium and high doses Yishen Paidu Formula groups,level of Klotho protein was obviously increased,which were more significant with dosage increase(P<0.05).Conclusion:Yishen Paidu Formula may alleviate inflammatory response in CRF rats by inhibiting Calcineurin/NFAT signaling pathway.

Objective:To explore the therapeutic mechanism of moxibustion in Crohn disease(CD)-associated intestinal fibrosis by observing its effects on the angiotensin-converting enzyme(ACE)/angiotensin Ⅱ(Ang Ⅱ)/angiotensin Ⅱ type 1 receptor(AT1R)axis in CD mouse models.Methods:Six randomly selected male C57BL/6 mice were assigned to a normal group,while the remaining mice were administered 0.1 mL of 2,4,6-trinitrobenzene sulfonic acid via enema to establish a CD intestinal fibrosis model.After successful modeling,the mice were randomly divided into a model group,a moxibustion group,and a Western medication group,with 6 rats in each group.The normal group and the model group only received grabbing without intervention.In the moxibustion group,mild moxibustion was applied to Qihai(CV6)and bilateral Tianshu(ST25)once a day for 10 min each time over 7 consecutive days.The Western medication group was administered mesalazine suspension via oral gavage once a day for 7 consecutive days.At the end of the intervention,the general condition,disease activity index(DAI)score,and gross colon score of mice in each group were evaluated.Hematoxylin-eosin staining was used to observe and score the histological changes in the colon tissue in each group.Masson staining was used to observe colonic fibrosis and the ratio of collagen-positive areas was analyzed;the expression of Ang Ⅱ in the colon tissue was detected by the enzyme-linked immunosorbent assay;immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction were used to detect the protein and mRNA expression of ACE and AT1R in the colon tissue,respectively;Western blotting was used to detect the expression of transforming growth factor(TGF)-β1 and connective tissue growth factor(CTGF)in the colon tissue.Results:Compared to the normal group,the DAI score,gross colon score,colonic histological score,collagen-positive area ratio,ACE protein and mRNA,Ang Ⅱ protein,AT1R protein and mRNA,TGF-β1 protein,and CTGF protein in the colon tissue in the model group increased significantly(P<0.01).In contrast,the above indicators in both the moxibustion group and the Western medication group reduced significantly compared to the model group(P<0.01 or P<0.05).There was no statistical difference in these indicators between the moxibustion group and the Western medication group(P>0.05).Conclusion:Moxibustion can alleviate intestinal fibrosis in CD mice,and its therapeutic mechanism may be associated with the regulation of colonic ACE/AngⅡ/AT1R axis.

Objective To investigate the incidence and adverse prognosis of late onset sepsis(LOS)in neonates in neonatal intensive care unit(NICU).Methods A retrospective study was conducted to collect and analyze the peri-natal condition,underlying diseases,invasive procedures,and adverse prognosis of neonates in NICU of a regional maternal and child healthcare hospital from 2019 to 2023.According to whether LOS occurred during hospitaliza-tion,neonates were divided into LOS group and non-LOS group.The LOS group was divided into 5 subgroups based on whether invasive procedures were performed:LOS plus umbilical vein catheter(UVC)group,LOS plus peripherally inserted central catheter(PICC)group,LOS plus sequential catheter group,LOS plus tracheal intuba-tion group,and LOS plus lumbar puncture group,the relationship between LOS and adverse prognosis was ana-lyzed.Results Among 2 945 neonates in NICU,354(12.02％)developed LOS.Comparison between LOS groups and non-LOS group were as follows:in term of perinatal condition of neonates,there were statistically significant difference in weight,gestational age,and whether they were twins between the two groups(all P＜0.001);in term of underlying diseases,there were statistically significant differences in the number of cases of maternal gestational hypertension,neonatal asphyxia,neonatal congenital heart disease,neonatal ventricular dilation,neonatal pneumo-nia,neonatal hyperthyrotropinemia,and neonatal anemia,as well as five invasive procedures between the two groups(all P＜0.05).Compared with the non-LOS group,the incidences of retinopathy of prematurity(ROP),neonatal necrotizing enterocolitis(NNEC),bronchopulmonary dysplasia(BPD),and neonatal respiratory distress syndrome(NRDS)in LOS group were all higher(all P＜0.001).Regression analysis showed that compared with the non-LOS groups,the risk of ROP increased in the LOS group and its subgroups,with the LOS plus sequential catheter group having a 2.27-fold higher risk of ROP than non-LOS group;the risk of NNEC increased in the LOS group and its subgroups,with the LOS plus UVC group having an 8.29-fold higher risk of NNEC than the non-LOS group.Except for the LOS plus UVC group,the risk of BPD increased in the LOS group and other subgroups,with the LOS plus PICC group and LOS plus sequential catheter group having 4.68-and 4.64-fold higher risk of BPD than the non-LOS group,respectively;the risk of NRDS in the LOS plus PICC group was 6.84-fold higher than the non-LOS group(all P＜0.05).The top three pathogens causing LOS were coagulase negative Staphylococcus,Klebsiella pneumoniae,and Escherichia coli.Conclusion LOS can significantly increase the risks of ROP,NNEC,BPD,and NRDS.LOS plus invasive procedures can further increase the risk of adverse prognosis.