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 investigate the common genotypes and distribution characteristics of thalassemia in Guiyang region, and preliminarily analyze the rare mutations of globin genes in this area. METHODS: A total of 9 334 individuals who came to our hospital for thalassemia screening from June 2016 to February 2023 were included in this study. They were examined for common thalassemia mutations using PCR-based flow-through hybridization technology. Meanwhile, rare and unknown mutations were detected by Sanger sequencing. RESULTS: Among the 9 334 cases, 895 positive cases of common thalassemia were detected, with a positive rate of 9.59%. Among the positive samples, 565 cases (63.13%) were confirmed to be α thalassemia, of which the most common genotypes were αα/-α^3.7 (46.37%), followed by αα/--^SEA(26.55%) and αα/-α^4.2(10.62%); 310 cases (34.64%) were diagnosed as β thalassemia, with β^CD17/β^N (39.35%) being the most frequent genotype, followed by β^CD41-42 /β^N (31.29%) and β ^IVS-II-654/ β^N (12.90%). There were 20 cases (2.23%) of αβ complex thalassemia, mainly being αα/-α^3.7 combined with β^CD17 /β^N . Additionally, 8 cases of rare globin gene mutations were found by Sanger sequencing, including 7 mutation types. Among them, HBB: c. -137C> T (-87 C>T) was reported for the first time in Guizhou; HBA1 : c.*29C>T and HBB : c. 93-50C>T (IVS I-81C>T) were new mutations that had not been recorded in either the HbVar or IthaGenes database. CONCLUSION Guiyang region has a high incidence of thalassemia mutations, and these mutations are diverse and complex. Analyzing gene mutation types of thalassemia in this area can contribute to the prevention of the birth of children with severe thalassemia.
Humans ; Genotype ; Mutation ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Thalassemia/epidemiology* ; Genetic Testing ; China/epidemiology* ; Male ; Female

Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording; this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.
Animals ; CA1 Region, Hippocampal/physiology* ; Male ; Association Learning/physiology* ; Neuronal Plasticity/physiology* ; Cues ; Memory/physiology* ; Synapses/physiology* ; Conditioning, Classical/physiology* ; Excitatory Postsynaptic Potentials/physiology* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Rats ; Optogenetics

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Objective Through the investigation of Tongxuan Lifei prescription and Tongxuan Lifei prescription to reduce Ephedrae Herba on the respiratory system,central system,urinary system,circulatory system and digestive system of model rats with wind-cold superficies symptoms,to explore the effect of the ascending and floating of Ephedrae Herba on the efficacy of Tongxuan Lifei prescription and to provide theoretical basis for clinical prescription.Methods 60 SD rats were randomly divided into normal group(CON),model group(M),paracetamol group(Y,0.455 g·kg-1),Ephedrae Herba group(MH,2.340 g·kg-1),Tongxuan Lifei prescription group(TX,4.326 g·kg-1)and Tongxuan Lifei prescription to reduce Ephedrae Herba group(TX-MH,3.920 g·kg-1),10 rats in each group.Except for the CON group,the rats of the groups were modeled with fan blowing and cold stimulation.The model was successful when the rats appeared in a state of crouching or condensed,decreased spontaneous activity,hunched back,sneezing,and elevated body temperature.After successful modeling,the corresponding drugs(10 mL·kg-1)were given respectively,and the rats in the CON and M group were given the same volume of distilled water for 4 consecutive days.The basic state of the rats was observed,ammonia induced cough,phenol red excretion and levels of inflammatory factors(IgE,IL-4,IFN-γ)in BALF,lung histopathological sections and oxidative stress(MDA,SOD and GSH-Px)levels were determined to investigate the effects of TX and TX-MH on the respiratory system.The effects of TX and TX-MH on the central system were investigated by the open field experiment,the sleep time of rats and the levels of inflammatory factors(IgE,IFN-γ,IL-4)in serum.The effects of TX and TX-MH on digestive system were investigated by gastrointestinal motility and levels of motilin(MTL),somatostatin(SST)and gastrin(GT)in plasma.The effects of TX and TX-MH on the urinary system were investigated by the levels of toe sweat secretion,urine volume,serum creatinine(CRE)and blood urea nitrogen(BUN).The effects on the circulatory system were investigated by the rat cardiac function and the levels of serum NO.Results TX could increase the body weight and decrease the body temperature of rats with wind-cold superficies symptoms;TX could stimulate the central system,improve the respiratory system,enhance the urinary-sweat system,and has no obvious effect on the circulatory system and digestive system.The effects of TX-MH on the respiratory system and the central system is obviously weakened,and the circulatory system and the digestive system are basically not affected.In general,the effect of TX is better than that of TX-MH,which indicates that the removal of Ephedrae Herba,the ascending and floating medicine,weakens the effect of TX on"promoting cold"and"xuanfei relieving cough".Conclusion The Ephedrae Herba's ascending and floating medicinal properties play an important role in the efficacy of Tongxuan Lifei prescription's"promoting cold"and"xuanfei relieving cough".

Objective:To evaluate the regeneration and biomechanical property recovery of semitendinosus tendon(ST)/gracilis tendon(GT) after anterior cruciate ligament(ACL) reconstruction using shear wave elastorgraphy (SWE) combined with high-frequency ultrasound(HFUS).Methods:Twenty-five patients who underwent ST/GT autograft reconstruction after ACL rupture at the People′s Hospital of Guangxi Zhuang Autonomous Region from January 2020 to June 2022 were prospectively enrolled. All patients underwent HFUS, SWE and flexion strength assessment at pre-operation and 1, 3, 6, 12, 24 months postoperatively. The morphology, length, cross-sectional area and SWE of ST/GT and flexion strength of knee were recorded at each time point. Repeated measures analysis of variance was employed to compare the cross-sectional area and elasticity value of regenerated ST/GT at different time points. Spearman correlation analysis was used to investigate the relationship between the elasticity value of regenerated ST/GT and flexion strength.Results:The regeneration rates of ST/GT after being harvested for ACL reconstruction were 88% and 92%. The length of the regenerated ST/GT were shorter than before operation(both P<0.05). Repeated measures analysis of variance revealed significant differences in the cross-sectional area of regenerated ST/GT, both in terms of time effect and inter-group effect ( F=27.264, 28.980; both P<0.001), but no significant difference was observed in the interaction effect ( F=0.670, P=0.652). The cross-sectional area of regenerated ST/GT was the largest at 3 months postoperatively ( P<0.05), and restored to the preoperative level at 12 and 24 months postoperatively (both P>0.05). Repeated measures analysis of variance showed that the elasticity values of the regenerated ST/GT were significantly different in terms of time effect, group effect, and interaction effect ( F=265.402, 33.015, 11.475; all P<0.001). The elasticity of regenerated ST/GT post-operation gradually increased over time. The flexion strength level of knee gradually improved post-operation(χ 2=34.83, P<0.001). The elasticity values of the regenerated ST and GT showed significant positive correlations with the flexion strength ( rs=0.755, 0.761; both P<0.001). Conclusions:HFUS discovers that most of ST/GT can be regenerated after being harvested for ACL reconstruction. The flexion strength and elasticity value of regenerated tendon recover gradually with time. It is suggested that the SWE can predict the recovery of biomechanical property of regenerated ST/GT.

The limitations of antifungal drugs and severe drug resistance make the treatment of invasive fungal infections (IFIs) a great challenge. Itraconazole (ITZ), as a clinical first-line drug, has a wide range of antifungal activity, but it is still limited by adverse reactions such as liver and kidney toxicity, headache and abdominal pain due to its poor water solubility and easy to cause drug accumulation by injection. In this study, the amphiphilic polymer gallic acid-chitosan-cinnamaldehyde (GA-CS-CN) was prepared by amide reaction and Schiff-base reaction. The drug-loaded nanoparticles (GA-CS-CN/ITZ) were prepared by ultrasonic method. The properties of nanoparticles formulations and its in vitro antifungal activity were investigated in the study. Studies have shown that GA-CS-CN/ITZ is spherical, homogeneous and stable, and has good biological safety. The average particle size was 239.57 ± 31.37 nm, ITZ encapsulation efficiency was (93.41 ± 1.12)%, and the cumulative drug release was (62.25 ± 1.88)% at 48 h in vitro. The antifungal activity results of Candida albicans ATCC 10231 (C. albicans) showed that it had the optimal antifungal effect and could significantly enhance the antifungal activity of free drugs. GA-CS-CN/ITZ prepared in this study has excellent biological safety and anti-C. albicans performance, which provides a new choice for the treatment of C. albicans infection and has good application potential in the treatment of this fungal infection.