Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective To introduce the causes of accidents and the diagnosis and treatment of two patients with radiation-induced skin injury admitted to our hospital in 2023, and to provide a reference for the clinical treatment of subsequent radiation-induced skin injury. Methods The clinical treatment process of two patients with acute skin injury caused by external radiation exposure were summarized and analyzed. Results The exposure history of the two patients was reconstructed, the flaw detection scenario was simulated, the biological dose and hand skin exposure dose were estimated, and the infrared thermal imaging device was used for dynamic monitoring. A comprehensive analysis was conducted based on clinical manifestations and other data. The diagnosis of “Xie” was excessive exposure combined with acute radiation-induced skin injury on both hands (Grade IV for the right hand palm, index finger, and middle finger and Grade II for the left hand little finger). The diagnosis of “Hao” was acute radiation-induced skin injury on both hands (Grade I). The two patients received different clinical treatment measures: “Xie” was treated with both local and systemic therapies, while “Hao” was mainly treated with systemic therapy. Conclusion After systematic and effective treatment, the radiation-induced skin injuries healed in both patients.

BACKGROUND:Studies have shown that patients with premature ovarian failure have changes in the structure of intestinal flora and that imbalance of intestinal microbiota may be one of the important mechanisms in the development of premature ovarian failure. OBJECTIVE:To investigate the effect of Liuwei Dihuang Wan on oxidative stress and intestinal microbiota in premature ovarian failure mice induced by cyclophosphamide. METHODS:Forty-five female ICR mice were randomized into three groups:blank group(normal mice),model group(premature ovarian failure mice),and Liuwei Dihuang Wan group.A mouse model of premature ovarian failure was prepared by one-time intraperitoneal injection of cyclophosphamide(120 mg/kg)in the latter two groups.After successful modeling,the Liuwei Dihuang Wan group was intragastrically administered for 28 continuous days,and the other two groups were intragastrically administered with the same amount of normal saline for 28 days.Mouse body mass was recorded weekly and ovarian index was calculated.The development of mouse follicles was observed using hematoxylin-eosin staining.ELISA method was used to detect serum levels of anti-Mullerian hormone,estradiol,follicle stimulating hormone,superoxide dismutase,glutathione peroxidase,and malondialdehyde.Meanwhile,the gut microbiome of all mice was detected through 16S rDNA sequencing. RESULTS AND CONCLUSION:The mice in the model group had loose hair,decreased vigor and grip strength,almost no increase in body mass,and decreased ovarian index.Whereas,the mouse body mass and ovarian index were increased after treatment with Liuwei Dihuang Wan(P<0.05).The estrous cycle of mice in the model group was disorganized;Liuwei Dihuang Wan could restore the estrous cycle and reduce the number of atretic follicles in mice with premature ovarian failure.The serum levels of follicle stimulating hormone and malondialdehyde in the model group significantly increased(P<0.01),while the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase significantly decreased(P<0.01).Liuwei Dihuang Wan could significantly decrease the serum levels of follicle stimulating hormone and malondialdehyde(P<0.01),and increase the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase.According to the 16S rDNA sequencing results,Liuwei Dihuang Wan could regulate the abundance and diversity of intestinal microbiota,and increase the relative abundance of beneficial bacteria.KEGG pathway analysis showed that the intestinal microbiota and metabolic pathways,biosynthesis of secondary metabolites,microbial metabolism in different environments,and biosynthesis of amino acids were regulated by Liuwei Dihuang Wan.To conclude,the changes in the structure of intestinal microbiome may be one of the potential mechanisms of Liuwei Dihuang Wan in treating premature ovarian failure.Liuwei Dihuang Wan can regulate the structure of intestinal microbiome,increase the number of beneficial bacteria,reduce the number of harmful bacteria,and thus improve the balance of intestinal microbiota.This regulatory effect helps to reduce oxidative stress levels and further inhibit ovarian oxidative stress in mice with premature ovarian failure.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective To investigate the effectiveness of the integrated schistosomiasis control programme in Sichuan Province during the stage moving from transmission interruption to elimination (2015—2023), so as to provide insights into formulation of the schistosomiasis control measures during the post-elimination stage. Methods Schistosomiasis control data were retrospectively collected from departments of health, agriculture and rural affairs, forestry and grassland, water resources, and natural resources in Sichuan Province from 2015 to 2023, and a database was created to document examinations and treatments of human and livestock schistosomiasis, and snail survey and control, conversion of paddy fields to dry fields, ditch hardening, rivers and lakes management and building of forests for snail control and schistosomiasis prevention. The completion of schistosomiasis control measures was investigated, and the effectiveness was evaluated. Results A total of 20 545 155 person-times received human schistosomiasis examinations in Sichuan Province during the period from 2015 to 2023, and 232 157 person-times were seropositive, with a reduction in the seroprevalence from 2.10% (44 299/2 107 003) in 2015 to 1.12% (9 361/837 896) in 2023 (χ² = 7.68, P < 0.001). The seroprevalence of human schistosomiasis appeared a tendency towards a decline in Sichuan Province over years from 2015 to 2023 (b = −8.375, t = −10.052, P < 0.001); however, no egg positive individuals were identified during the period from 2018 to 2023, with the prevalence of human Schistosoma japonicum infections maintained at 0. Expanded chemotherapy was administered to 2 754 515 person-times, and medical assistance of advanced schistosomiasis was given to 6 436 persontimes, with the treatment coverage increasing from 46.80% (827/1 767) in 2015 to 64.87% (868/1 338) in 2023. Parasitological tests for livestock schistosomiasis were performed in 35 113 herd-times, and expanded chemotherapy was administered to 513 043 herd-times, while the number of fenced livestock decreased from 121 631 in 2015 to 103 489 in 2023, with a reduction of 14.92%. Snail survey covered 433 621.80 hm² in Sichuan Province from 2015 to 2023, with 204 602.81 hm² treated by chemical control and 4 637.74 hm² by environmental modifications. The area of snail habitats decreased from the peak of 5 029.80 hm² in 2016 to 3 709.72 hm² in 2023, and the actual area of snail habitats decreased from the peak of 8 585.48 hm² in 2016 to 473.09 hm² in 2023. The mean density of living snails remained low across the study period except in 2017 (0.62 snails/0.1 m²). Schistosomiasis control efforts by departments of agriculture and rural affairs in Sichuan Province included conversion of paddy fields to dry fields covering 153 346.93 hm², hardening of 6 110.31 km ditches, building of 70 356 biogas digesters, replacement of cattle with 227 161 sets of machines, and captive breeding of 21 161 070 livestock from 2015 to 2023, and the control efforts by departments of water resources included rivers and lakes management measuring 5 676.92 km and renovation of 2 331 irrigation areas, while the control efforts by departments of forestry and grassland included building of forests for snail control and schistosomiasis prevention covering 23 913.33 hm², renovation of snail control forests covering 8 720 hm² and newly building of shelterbelts covering 764 686.67 hm². All 63 endemic counties (cities and districts) had achieved the criterion for schistosomiasis elimination criteria in Sichuan Province by the end of 2023. Conclusion Following the integrated control efforts from 2015 to 2023, remarkable achievements have been obtained in the schistosomiasis control programme in Sichuan Province, with all endemic counties successfully attaining the schistosomiasis elimination target at the county level.

OBJECTIVE To investigate the efficacy and safety of metformin in the treatment of diabetes mellitus type 2 （T2DM） complicated with sarcopenia in elderly patients. METHODS From January 2022 to January 2024， clinical data from eligible patients with T2DM complicated with sarcopenia treated at the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College were collected. Patients were randomly assigned into control group （70 cases） and observation group （70 cases） using a random number table. Both groups received routine interventions； control group additionally received subcutaneous injections of Insulin glargine injection before bedtime and Human insulin injection 30 minutes before breakfast， lunch and dinner every day. In addition to the same treatments as the control group， the observation group was administered 0.5 g of Metformin hydrochloride sustained-release tablets orally once daily. Both groups were treated continuously for 24 weeks. Comparisons were made between the two groups in terms of glucose metabolism indexes [fasting blood glucose （FBG）， 2 h postprandial blood glucose （2 hBG）， and glycosylated hemoglobin （HbA1c）]， homeostasis model assessment of insulin resistance （HOMA-IR）， appendicular skeletal mass muscle index （ASMI）， grip strength， walking speed， lipid metabolism indexes [serum total triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）]， serological markers [high-sensitivity C reactive protein （hs-CRP）， interleukin-6 （IL-6）， and ferritin levels] and quality of life. The occurrence of ADR was recorded in both groups. RESULTS 65 patients in the control group and 63 patients in the observation group completed this study， respectively. After treatment， the levels of FBG， 2 hBG， HbA1c， HOMA-IR，TG and TC in both groups， and the levels of hs-CRP， IL-6 and ferritin in observation group were all significantly reduced compared to those before treatment （P＜0.05）， and the HOMA-IR in observation group was significantly lower than control group （P＜0.05）； additionally， the grip strength， walking speed， and scores for daily living and activity abilities of observation group were increased than those before treatment and the control group （P＜0.05）. The incidence of adverse drug reactions in both groups was 2.86%. CONCLUSIONS Metformin can reduce inflammatory factors and ferritin levels， promote the recovery of muscle mass and strength， improve insulin resistance， and quality of life in elderly patients with T2DM complicated with sarcopenia， and does not increase the occurrence of adverse drug reactions.

Objective:To investigate the value of the five-sectional screening method of the central nervous system（CNS）in early detection of fetal CNS abnormalities during the first trimester.Methods:The data of pregnant women who underwent nuchal translucency（NT）screening at the Affiliated Suzhou Hospital of Nanjing Medical University from September 2018 to September 2023 were retrospectively analyzed. And a five-sectional screening method of CNS was performed in all fetuses at the meantime. The five-sectional screening protocol in the first trimester consists of the mid-sagittal plane of the fetal head，trans-ventricular plane，trans-thalamus plane，axial plane of the fetal head at the posterior fossa level，and the sagittal plane of the fetal spine. All fetuses underwent ultrasound screening during the second trimester and the third trimester sequentially after NT screening. All the ultrasound findings were tracked，and all fetuses were followed up until delivery or after induction. Fetuses with CNS abnormalities found or suspected in the first trimester were reviewed by at least one senior physician，and follow-up examinations were routinely performed after 2 weeks to further confirm the diagnosis or find other abnormalities that may be present.Results:A total of 13 679 fetuses were screened，included 11 415 singleton pregnancies and 1 132 twin pregnancies. Among them，there were 289 cases of missed follow-up and unexplained fetal death，included 263 singleton pregnancies and 13 twin pregnancies. A total of 13 390 fetuses were finally included，among which，35 cases developed CNS abnormalities with 34 cases detected by prenatal ultrasound and 1 case of closed spina bifida missed in prenatal diagnosis，and the detection rate of CNS malformation by prenatal ultrasound was 97.14%（34/35）. Of the 35 fetuses with CNS abnormalities，24 were detected by the CNS five-sectional screening method in the first trimester，with a sensitivity of 68.57%，a specificity of 100%，a positive predictive value of 100%，and a negative predictive value of 99.92%. Among them，there were 2 cases of anencephaly，3 cases of exencephaly and 6 cases of encephalocele were all detected in the first trimester. In addition，6 cases of holoprosencephaly，3 cases of severe ventriculomegaly，2 cases of open spina bifida，and 2 cases of Dandy-Walker malformation were detected in the first trimester. In this study，1 case of agenesis of corpus callosum（ACC），1 case of arachnoid cyst，1 case of lissencephaly，1 case of schizencephaly，and 1 case of mega cisterna magna were not detected in early pregnancy.Conclusions:The fetal five-sectional screening method of CNS in the first trimester has high specificity，positive predictive value and negative predictive value for the detection of fetal CNS abnormalities，but the sensitivity is moderate. The five-sectional screening method for CNS in early pregnancy may be an effective method for early detection of fetal CNS abnormalities.

Objective:To investigate the diagnostic value of fetal cardiac ultrasound view visualization in the first trimester for congenital heart disease（CHD）.Methods:A retrospective analysis was performed on 13 323 singleton fetuses who underwent first-trimester（11-13 +6 weeks）ultrasound screening at the Ultrasound Medicine Center，the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to June 2024. Cardiac views including the four-chamber view（4CV），left ventricular outflow tract view（LVOT），and Results:The study group showed significantly higher rates of "poorly visualized" 4CV，LVOT，and 3VT than the control group（2.70% vs. 0.14%， P=0.005；36.49% vs. 4.76%， P<0.001；36.49% vs.2.46%， P<0.001）. The efficacies of combination 1（any view abnormal）and combination 2（any view "poorly visualized" or "abnormal"）were comparable，with AUCs of 0.86 and 0.85（ P=0.424）. The AUCs of combination 3（3VT "poorly visualized" or any view "abnormal"）and combination 4（4CV "poorly visualized" or any view "abnormal"）were 0.88 and 0.86（ P=0.424），all significantly higher than combination 5（LVOT "poorly visualized" or any view "abnormal"，AUC=0.84，all P<0.05）. Conclusions:"Poorly visualized" cardiac views in the first trimester demonstrate good diagnostic efficacy for CHD，particularly when 3VT or 4CV are affected，warranting heightened clinical vigilance for fetal cardiac anomalies.