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 gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

The purpose of the present study was to investigate the effects of resistance combined with aerobic chrono-exercise on the common carotid artery elasticity and hemodynamics. 24 healthy young men (21.96±0.43 years old) underwent a single acute resistance combined with aerobic exercise intervention at eight time periods (6, 8, 10, 12, 14, 16, 18, and 20 o'clock). The axial flow velocity and diameter waveforms of the common carotid artery were measured, and the hemodynamics were calculated using the classical hemodynamic theory before exercise, immediately after exercise, 10 min and 20 min after exercise. The results showed that during exercise recovery, systolic and mean pressures decreased more markedly after exercise at 8 o'clock (P < 0.05); At 20 min post-exercise, arterial stiffness index and pressure-strain elastic modulus after exercise at 6 o'clock were reduced compared with the resting state, but were significantly elevated after exercise at 20 o'clock (P < 0.05). Immediately after exercise, the pressure rise was higher after exercise at 6 o'clock and the mean wall shear stress was higher after exercise at 20 o'clock (P < 0.05). These results suggest that resistance combined with aerobic chrono-exercise produces different effects on common carotid artery hemodynamics in young men. A single acute session of resistance combined with aerobic exercise at 8 o'clock is more effective in lowering blood pressure. Exercise at 6 o'clock is beneficial to improve arterial elasticity but is not recommended for young male individuals with cardiovascular disease risks because of the excessive increase in blood pressure immediately after exercise. Exercise at 20 o'clock is more effective in improving wall shear stress but is accompanied by elevated arterial stiffness indices and pressure-strain elastic modulus. These results provide a scientific basis for healthy young men in choosing the time of exercise by exploring the common carotid artery elasticity and hemodynamic-related indices.
Humans ; Male ; Young Adult ; Exercise/physiology* ; Carotid Artery, Common/physiology* ; Hemodynamics/physiology* ; Vascular Stiffness/physiology* ; Elasticity ; Resistance Training ; Adult

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

OBJECTIVE: To screen out the key metabolites related to diabetic foot (DF) by integrating genome-wide association studies (GWAS) and metabolome genome-wide association studies (mGWAS). METHODS: The literature databases such as PubMed and China national knowledge infrastructure(CNKI), as well as genomics databases such as PAN UKBB, FinnGen, and IEU Open GWAS were systematically retrieved from database estobilishment to November 2024 on DF-related single nucleotide polymorphisms and genome-wide association studies. DF-single nucleotide polymorphism-metabolite network was constructed by mGWAS package and mGWAS-Explorer platform. The causal relationship between key factors was evaluated by two-sample Mendelian randomization. The genetic correlation between DF and 575 metabolites (source:IEU Open GWAS) was evaluated by linkage disequilibrium score regression. In vitro experiments were conducted to induce injury of human umbilical vein endothelial cells with 30 mM glucose and intervene with 20 μM γ-tocopherol. Changes in cell migration, scratch healing and tube formation function were detected. RESULTS: Twenty-senen literatures on single nucleotide polymorphism literatures and 3 studies on GWAS were included. Genetic analysis results showed DF-related single nucleotide polymorphisms were enriched in vascular endothelial dysfunction-related pathways (such as fluid shear stress and atherosclerosis). The results of metabolic network analysis screened out 19 associated metabolites, among which 12 such as γ -tocopherol and pyruvate had significant genetic correlations with DF. Mendelian randomization suggested matrix metalloproteinase-9(MMP-9) might be a potential driver of DF (β=0.658, P=0.063 8), and the occurrence of DF could reduce the level of high-density lipoprotein (β=-0.002, P=0.015 2). The results of in vitro experiments confirmed that γ -tocopherol could improve endothelial dysfunction induced by high glucose, specifically manifested as an increase in the number of cell migrations, improvement in the scratch healing rate, and recovery of tubule formation ability (P<0.05). CONCLUSION DF has a genetic basis centered on vascular endothelial dysfunction, and its occurrence can lead to further metabolic disorders. The key single nucleotide polymorphism loci integrated provided molecular markers for the risk stratification of foot ulcers in diabetic patients. In addition, γ -tocopherol has demonstrated clinical application potential as a therapeutic drug for DF by significantly improving the function of vascular endothelial cells in a high-glucose environment.
Humans ; Diabetic Foot/drug therapy* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Genomics ; Metabolomics ; Metabolome

OBJECTIVE: To explore clinical efficacy of membrane-induced technique combined with gastrocnemius muscle flap transposition in treating traumatic osteomyelitis of the upper tibia. METHODS: A retrospective analysis was conducted on 7 patients with traumatic osteomyelitis of the upper tibia who were treated with membrane-induced technique combined with gastrocnemius muscle flap transposition from January 2022 to December 2023. Among them, there were 4 males and 3 females; aged from 29 to 57 years old; 4 patients were treated after open fracture, 2 patients were treated after closed fracture, and 1 patient was treated after scalding; the courses of disease ranges from 2 weeks to 8 years; sinus tracts were present in all patients, and the lesion range of the tibia ranged from 5 to 9 cm. The results of deep tissue bacterial culture showed that 2 patients were negative, 3 patients were staphylococcus aureus, 1 patient was methicillin-resistant staphylococcus aureus, and 1 patient was pseudomonas aeruginosa and 1 patient was klebsiella pneumoniae. After debridement, the range of bone defect ranged from 8 to 12 cm, and the cortical defect accounted for approximately 30% of the circumference. The area of soft tissue defect ranged from 8.0 cm×2.0 cm to 10.0 cm×6.0 cm. At the first stage, vancomycin-loaded/meropenem/gentamicin-loaded bone cement was implanted. The gastrocnemius muscle flap was repositioned to cover the wound surface and free skin grafting was performed. After an interval of 7 to 10 weeks, the stageⅡsurgery was performed to remove bone cement. Autologous iliac bone mixed with vancomycin/gentamicin and calcium sulfate artificial bone was transplanted, and the wound was sutured. One patient retained the original internal plants, one patient removed the internal plants and replaced them with steel plate external fixation, one patient replaced the internal plants and added steel plate external fixation, and three patients were simply fixed with steel plate external fixation. One year after operation, the recovery of knee joint and ankle joint functions was evaluated by using Hospital for Special Surgery (HSS) knee joint score and Kofoed ankle joint function score respectively. RESULTS: All patients had their wounds closed simultaneously with bone cement implantation and healed well. All patients were followed up for 12 to 17 months after operation, and satisfactory bone healing was achieved at 6 months after stageⅡsurgery. Twelve months after operation, all patients had good bone healing without obvious limping was observed when walking. At 12 months after operation HSS knee joint score ranged from 93 to 100 points, and Kofoed ankle function score ranged from 96 to 100 points. CONCLUSION For traumatic osteomyelitis of the upper tibia, a staged treatment plan combining membrane-induced technique and gastrocnemius flap transposition on the basis of thorough debridement could safely cover the wound surface, effectively control bone infection and achieve satisfactory bone healing, without adverse effects on limb function.
Humans ; Male ; Female ; Middle Aged ; Osteomyelitis/surgery* ; Adult ; Surgical Flaps ; Retrospective Studies ; Tibia/injuries* ; Muscle, Skeletal/surgery*

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome