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.

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Non-steroidal anti-inflammatory drugs(NSAIDs),commonly utilized analgesics,are extensively employed for managing pain associated with musculoskeletal disorders or injuries.Recent clinical studies have demonstrated a heightened risk of bone stress injuries(BSI)in soldiers and athletes,particularly during high-intensity training,due to NSAID usage.Furthermore,the impact of NSAIDs on fracture healing is well-documented;however,the precise mechanism by which their use during training contributes to an increased incidence of stress bone injuries remains unclear.This article aims to summarize potential mechanisms through an extensive review of domestic and international literature in order to standardize the utilization and clinical management of NSAIDs,optimize pain management strategies,and prevent stress bone injuries or fractures in specific populations such as soldiers and elite athletes.

Heat stroke is a heat-related illness caused by an imbalance between the body's heat production and heat dissipation,which could lead to multiple organ dysfunction syndrome with a high mortality rate.Rapid and effective reduction of core body temperature is key to successful treatment.This article reviews recent progress in the treatment of heat stroke,including new understandings of organ injury mechanisms,the timing,velocity and goals of cooling treatment,evaluation and selection of traditional cooling techniques(such as cold water immersion),and scientific evaluation of new cooling technologies(such as blood purification technology and intravascular heat exchange cooling technology),aiming to promote understanding and treatment of heat stroke.

Objective:To investigate the genetic causal relationship of leukocyte telomere length(LTL)with prostatitis,orchi-tis and epididymitis by two-sample Mendelian randomization(MR).Methods:Using LTL as the exposure factor and prostatitis,or-chitis and epididymitis as outcome factors,we mined the Database of Genome-Wide Association Studies(GWAS).Then,we analyzed the causal relationship of LTL with prostatitis,orchitis and epididymitis by Mendelian randomization using inverse variance weighting(IVW)as the main method and weighted median and MR-Egger regression as auxiliary methods,determined the horizontal multiplicity by MR-Egger intercept test,and conducted sensitivity analysis using the leaving-one-out method.Results:A total of 121 related sin-gle nucleotide polymorphisms(SNPs)were identified in this study.IVW showed LTL to be a risk factor for prostatitis(OR=1.383,95％CI:1.044-1.832,P=0.024),and for orchitis and epididymitis as well(OR=1.770,95％CI:1.275-2.456,P=0.000 6).Conclusion:Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis,orchitis and epididymitis.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

Aim To explore the specific mechanism by which scutellarin(Scu)antagonizes the injury of human aortic endothelial cells(HAEC)induced by 2,2-azobis(2-methylpropylimidate)dihydrochloride(AAPH)by regulating the protein kinase RNA-like endoplasmic reticulum kinase(PERK)-nuclear factor erythroid 2-related factor 2(NRF2)/ac-tivating transcription factor 4(ATF4)-C/EBP homology protein(CHOP)pathway.Methods HAEC were pre-pro-tected by Scu and then injured by AAPH to explore the molecular mechanism of Scu on HAEC injury.The cells were di-vided into control group,AAPH group,AAPH+Scu low,medium and high groups.The contents of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and glutathione S-transferase(GSH-ST)in the cells were measured.The content of reactive oxygen species(ROS)in cells was detected by fluorescent probe,and the apop-tosis rate was detected by Annexin V-FITC/PI method.The mRNA expression of PERK and eIF2α in cells was detected by RT-qPCR.The protein expression of glucose regulated protein 78(GRP78),PERK,p-PERK,eukaryotic initiation factor 2α(eIF2α),p-eIF2α,ATF4,CHOP,Nrf2,Bcl-2,p53 up-regulated modulator of apoptosis(PUMA),Caspase-3 and Caspase-12 in cells was detected by Western blot.In order to further study the molecular mechanism of Scu against HAEC injury,gene silencing technology was used to inhibit the expression of PERK in HAEC.The cells were divided in-to five groups:control group,AAPH+si-con group,AAPH+Scu+si-con group,AAPH+si-PERK group,AAPH+si-PERK+Scu group.The mRNA expression of PERK and eIF2α in cells after si-PERK interference was detected by RT-qPCR.The protein expression of PERK,p-eIF2α,eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,Caspase-3 and Caspase-12 in cells after si-PERK interference was detected by Western blot.Results The content of ROS and the rate of apoptosis were significantly reduced after Scu intervention(P＜0.01).Scu could down-regulate the mRNA expression of PERK and eIF2α,and down-regulate the protein expression of GRP78,p-PERK,p-eIF2α,ATF4,CHOP,PUMA,Caspase-3,Caspase-12 and up-regulate the protein expression of Nrf2 and Bcl-2(P＜0.01).After interference with si-PERK,there were significant differences in the protein expression of PERK,p-eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,Caspase-3,Caspase-12,as well as the mRNA expression of PERK and eIF2α in cells compared to before interference(P＜0.01).It is proved that Scu could anti-endoplasmic role in reticulum stress and apoptosis,which is closely associated with the regula-tion of the PERK-Nrf2/ATF4-CHOP pathway.Conclusion Scu can effectively alleviate AAPH-induced injury to HAEC by regulating PERK-Nrf2/ATF4-CHOP pathways to inhibit endoplasmic reticulum stress and cell apoptosis.

Lens injury is an important etiological factor in the reduction of visual function following ocular trauma.Currently, there are no clear standards for the classification of lens injury, and comprehensive diagnostic tools are lacking.This deficiency leads to numerous controversies and challenges in critical areas, such as diagnosis and preoperative evalution, timing of surgery, surgical strategy, and assessment of postoperative prognosis.Tomographic imaging technology, such as computed tomography, magnetic resonance imaging, optical coherence tomography, has introduced a new dimension to the evaluation of lens injury, which is crucial for assessing the transparency, texture, location, morphology, and integrity of the lens, as well as the zonules and nearby intraocular structures.However, the use of tomographic imaging technology is somewhat limited due to the limitations of relying on a single method.With the ongoing advancement of imaging technologies and the rapid development of big data and artificial intelligence, tomographic imaging will become an increasingly essential tool in the future management of lens injury.Our expert group reviewed the epidemiological characteristics and classification of lens injury and the major challenges currently faced in the diagnosis and treatment of lens injury, and provided expert recommendations mainly focusing on the application, shortcomings and limitations of current tomographic imaging technology in the diagnosis and treatment of lens injury, and future development directions.

Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".