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.

ObjectiveTo investigate the value of intestinal fatty acid-binding protein （I-FABP） in predicting 6-week mortality in patients with liver cirrhosis after successful endoscopic hemostasis for esophagogastric variceal bleeding （EVB）. MethodsA retrospective analysis was performed for the clinical data of 207 patients with liver cirrhosis who underwent successful endoscopic treatment for EVB （including ligation and sclerotherapy） in The Affiliated Hospital of Yanbian University from September 2020 to June 2025， with the endpoint of 6-week bleeding-related mortality. ELISA was used to measure the serum level of I-FABP on admission， and a stratified analysis was performed based on the quartiles of I-FABP measurements. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier survival analysis， Cox regression analysis， and restricted cubic spline （RCS） curve were used to investigate the association between I-FABP and mortality. Machine learning models were used to further quantify the impact of I-FABP on mortality. The integrated Brier score and an integrated cumulative/dynamic area under the curve were used to assess the importance of time-dependent variables， and the receiver operating characteristic （ROC） curve was used to assess the performance of the predictive model. ResultsDuring the study， 29 patients （14.0%） died within 6 weeks after successful endoscopic hemostasis， with a median time to death of 16 （8—26） days. The mortality group had a significantly higher serum level of I-FABP than the survival group （Z=-3.731， P<0.001）. The Kaplan-Meier survival analysis showed that there was a significant difference in 6-week mortality between the groups of patients based on I-FABP quartiles （χ²=12.78， P=0.005）. The multivariable Cox regression analysis showed that an increase in I-FABP （hazard ratio=1.87， P=0.003） was an independent influencing factor for 6-week mortality. The RCS analysis showed a linear relationship between I-FABP and 6-week mortality （P_non-linear=0.280， P_overall=0.029）. Machine learning models showed that there was a dynamic change in the importance of I-FABP over time， and Brier score loss and the loss of cumulative/dynamic area under the curve after permutation showed that I-FABP was an important variable affecting 6-week mortality rate. ConclusionI-FABP level is independently associated with the risk of 6-week mortality endoscopic hemostasis for EVB in patients with liver cirrhosis， and therefore， it can be used as a potential biomarker for poor short-term prognosis.

ObjectiveTo analyze the effects of the progestin-primed ovarian stimulation （PPOS） protocol on embryo euploidy rate and clinical pregnancy outcomes in infertile patients. MethodsWomen who underwent Preimplantation genetic testing for aneuploidy （PGT-A） cycles were selected as study participants （a total of 656 cycles and 3 081 blastocysts）. Participants were divided into two age groups （≤35 years and >35 years） and further stratified by ovarian stimulation protocol： the Progestin-Primed Ovarian Stimulation （PPOS） group （n=48 and 60， respectively）， the Luteal Phase Long Protocol （LP） group （n=160 and 57， respectively）， and the Gonadotropin-Releasing Hormone Antagonist Protocol （AP） group （n=220 and 111， respectively）. Baseline characteristics， ovarian stimulation outcomes， and embryo development parameters were compared among the three protocols within each age group. Additionally， clinical pregnancy outcomes of the first frozen embryo transfer （FET） cycle were compared. The primary outcome measure was the embryo euploidy rate. Results① In the ≤35 years age group， baseline follicle-stimulating hormone （bFSH） levels were significantly higher in the PPOS group compared to the LP and AP groups， and the bFSH/bLH ratio was significantly higher in the PPOS group than in the AP group （P < 0.05）. In the >35 years age group， bFSH levels in both the PPOS and AP groups were significantly higher than in the LP group （P < 0.05）.② In the ≤35 years group， there were no significant differences in the rates of metaphase II （MII） oocytes， 2-pronuclei （2 PN） zygotes， cleavage， 2 PN cleavage， blastocyst formation， high-quality embryos， or embryo euploidy between the PPOS group and either the LP or AP groups. However， the PPOS group showed significantly lower values for the following parameters compared to the other two groups： total oocytes retrieved， number of MII oocytes， number of 2 PN zygotes， number of cleaved embryos， number of 2 PN cleaved embryos， number of blastocysts formed， number of high-quality embryos， number of high-grade blastocysts， number of transferable embryos， number of cryopreserved embryos， number of biopsied blastocysts， number of euploid embryos， and the rate of obtaining at least one euploid embryo. In the >35 years group， no significant differences were observed among the PPOS， LP， and AP groups in the rates of MII oocytes， 2 PN cleavage， blastocyst formation， or in the number of euploid embryos， euploidy rate， and the rate of obtaining at least one euploid embryo. However， the PPOS group had significantly lower numbers of total oocytes retrieved， MII oocytes， 2 PN zygotes， cleaved embryos， 2 PN cleaved embryos， blastocysts formed， transferable embryos， and cryopreserved embryos compared to the LP group （P<0.05）. The high-quality embryo rate was significantly lower in the PPOS group than in the AP group （P<0.05）. The numbers of high-quality embryos， high-grade blastocysts， and biopsied blastocysts were significantly lower in the PPOS group than in both the LP and AP groups （P<0.05）. Notably， the 2 PN fertilization rate was significantly higher in the PPOS group than in the AP group， and the cleavage rate was significantly higher in the PPOS group than in both the LP and AP groups （P<0.05）.③ No significant differences were found among the three groups in the biochemical pregnancy rate， clinical pregnancy rate， live birth rate， early miscarriage rate， and late miscarriage rate following the first FET cycle. ConclusionCompared to the other two protocols， the PPOS protocol does not significantly affect embryo euploidy or clinical pregnancy rates. However， in freeze-all cycles with PGT-A， the PPOS protocol does not reduce the rate of chromosomally normal embryos but may decrease the total number of available embryos. It may not be the optimal choice for younger women， but it can be considered as a viable option for women of advanced maternal age.

Objective: To investigate the ability of different concentrations of piceatannol (PIC) solution to biomodify decalcified dentin matrices in primary teeth, thereby providing a theoretical basis for improving the durability of resin-dentin bonding. Methods: This study was approved by the Medical Ethics Committee of the institution. Molecular docking was performed to predict the interaction effects of PIC with type I collagen and matrix metalloproteinases (MMPs) in dentin. A total of 124 clinically extracted intact primary molars were selected due to retention; of these, 76 were prepared into 60 completely decalcified dentin beams and 24 dentin slices. The 60 beams were equally allocated for dry mass loss and swelling ratio testing (30 beams each). For both experiments, the beams were randomly divided into five groups (n = 6): a control group, 5% glutaraldehyde group, and 2.5, 5, and 10 mg/mL PIC solution groups. This was to evaluate the anti-enzymatic hydrolytic properties and mechanical performance of type I collagen. Of the 24 slices, 15 were assigned to the aforementioned five groups (n = 3) for Fourier-transform infrared spectroscopy (FTIR) to explore the cross-linking mechanism. The remaining nine slices were randomly divided into three groups (n = 3): distilled water group A (SEM examination prior to enzymatic hydrolysis), distilled water group B (SEM examination after enzymatic hydrolysis), and a 10 mg/mL PIC solution group (SEM examination after treatment with 10 mg/mL PIC and subsequent enzymatic hydrolysis). This was to evaluate the cross-linking effect on demineralized dentin collagen. The remaining 48 molars were fabricated into bonding specimens and randomly divided into four groups (n = 12): a control group (distilled water group) and 2.5, 5, and 10 mg/mL PIC groups. Immediate and aged shear bond strength (SBS) were measured, and failure modes were observed under a stereomicroscope to investigate the impact of different PIC concentrations on the bonding durability of primary tooth dentin. Results: Molecular docking revealed strong binding activity between PIC and type I collagen/MMPs via hydrogen bonds, electrostatic potential, and hydrophobic forces; the FTIR results confirmed hydrogen bond formation. In the dry mass loss test, mass loss rates in the 2.5, 5, and 10 mg/mL PIC groups were significantly lower than that in the control group (P < 0.05), with the 10 mg/mL PIC group showing the most optimized cross-linking effect. Swelling tests indicated that all three PIC concentrations reduced the swelling ratio of the demineralized matrix, effectively improving its mechanical properties. SEM showed that collagen from the 10 mg/mL PIC group retained its natural three-dimensional network post-enzymolysis, contrasting sharply with the disintegrated collagen in the enzymolyzed distilled water group B but resembling the morphology of the non-enzymolyzed distilled water group A. SBS results demonstrated that the 10 mg/mL PIC group exhibited significantly higher bond strengths than the control group in both the immediate and aged tests (P < 0.05); immediate SBS in the 10 mg/mL PIC group was also significantly greater than that in the 2.5 mg/mL PIC group (P < 0.05), while no other intergroup differences were found (P > 0.05). Failure mode analysis indicated predominantly mixed fractures, with the proportion of interfacial fractures decreasing as PIC concentration increased compared with the control group. Conclusion A 10 mg/mL PIC solution can effectively cross-link decalcified dentin matrices in primary teeth, enhancing the anti-enzymatic hydrolytic capacity and mechanical properties during clinical operation, thereby promoting bond strength and interface stability, which promises to improve the long-term durability of resin-dentin bonding.

Objective The aim was to evaluate the effects of efforts directed toward controlling Oncomelania hupensis snails on small environmental modification projects in Anqing City to provide a reference for comprehensively controlling O. hupensis in hilly areas where schistosomiasis is endemic. Methods Field and retrospective surveys were conducted to collect data using questionnaires. The data from 35 questionnaires on small-scale environmental modification projects in Anqing City and the effects of snail obtained from monitoring forms were sorted. The data were descriptively analyzed using basic information on environmental modifications and investment costs. The Wilcoxon signed-rank test was used to compare snail status before and after environmental interventions. The Friedman test was applied to evaluate the changes in snail populations in the years after environmental intervention. Non-parametric independent sample tests were adopted to compare differences in the effects of different environmental interventions, environmental characteristics, and between project and control areas. Results A total of 35 environments altered from 2017 to 2023, including the creation of 29 ditches,1 dry land, and 5 pond-weirs. The main environmental interventions included hardening of ditches and pond-weirs as well as tilling with intercropping. The average investment costs of mortared rubble masonry hardening and tilling with intercropping were the highest(147.10 yuan/m2)and lowest(4.62 yuan/m2), respectively. The pre-intervention snail-infested area was 78 900 m2, which decreased to 18 100 m2, a decrease of 77.06%. After environmental intervention, the density and rate of living snails significantly decreased on frames with snails(P<0.001). In ditch environments, the smoothness of the ditch walls and the presence of snails in the upper reaches did not significantly decrease the living snail density; however, the presence of cracks on the inner side of the ditches significantly impacted the decline in the rate(P<0.001). No significant difference was found in the rates at which the living snail density or snail frame occurrence decreased among different environmental modification method. The effects of brick masonry, concrete, and mortared rubble masonry on snail control were significantly stronger than those of chemical snail control(P<0.01), whereas no significant difference was found in the decline in these two rates between project areas using other modification method and control areas using chemical snail control. Conclusions Schistosomiasis-prevention-oriented environmental interventions effectively eliminate snails from hilly snail-infested areas. Cost-effective modification method should be selected based on the environmental type, and post-modification monitoring and maintenance must be strengthened to further increase snail control effectiveness.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation