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.

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

Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration. Syntaphilin (Snph), known for its potent mitochondrial anchoring action, has emerged as a significant inhibitor of both mitochondrial transport and axonal regeneration. Therefore, investigating the molecular mechanisms that influence the expression levels of the snph gene can provide a viable strategy to regulate mitochondrial trafficking and enhance axonal regeneration. Here, we reveal the inhibitory effect of microRNA-146b (miR-146b) on the expression of the homologous zebrafish gene syntaphilin b (snphb). Through CRISPR/Cas9 and single-cell electroporation, we elucidated the positive regulatory effect of the miR-146b-snphb axis on Mauthner cell (M-cell) axon regeneration at the global and single-cell levels. Through escape response tests, we show that miR-146b-snphb signaling positively regulates functional recovery after M-cell axon injury. In addition, continuous dynamic imaging in vivo showed that reprogramming miR-146b significantly promotes axonal mitochondrial trafficking in the pre-injury and early stages of regeneration. Our study reveals an intrinsic axonal regeneration regulatory axis that promotes axonal regeneration by reprogramming mitochondrial transport and anchoring. This regulation involves noncoding RNA, and mitochondria-associated genes may provide a potential opportunity for the repair of central nervous system injury.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Nerve Regeneration/physiology* ; Mitochondria/metabolism* ; Zebrafish Proteins/genetics* ; Axons/metabolism* ; Signal Transduction/physiology* ; Axonal Transport/physiology* ; Nerve Tissue Proteins/genetics*

Image 1.

Human cytomegalovirus (HCMV) poses a significant risk of neural damage during pregnancy. As the most prevalent intrauterine infectious agent in low- and middle-income countries, HCMV disrupts the development of neural stem cells, leading to fetal malformations and abnormal structural and physiological functions in the fetal brain. This review summarizes the current understanding of how HCMV infection dysregulates the Wnt signaling pathway to induce fetal malformations and discusses current management strategies.
Humans ; Cytomegalovirus Infections/virology* ; Wnt Signaling Pathway ; Pregnancy ; Female ; Cytomegalovirus/physiology* ; Pregnancy Complications, Infectious/virology* ; Congenital Abnormalities/virology* ; Animals

Objective: To review the current development of artificial intelligence (AI) technology in the field of transfusion medicine. Methods: A systematic search was conducted in the Clarivate Web of Science Database from inception to December 2024 for literature related to AI and transfusion. A total of 4 775 publications were identified. Based on inclusion and exclusion criteria, 133 original studies were ultimately included and analyzed using a narrative synthesis approach. Results: Research on AI in transfusion has surged since 2020 (accounting for 77% of all publications), with China ranking second globally in publication volume. Among the included studies, 69.2% focused on predicting individual transfusion needs, followed by inventory management (8.3%), diagnosis and prediction of adverse transfusion reactions (6.0%), factors influencing transfusion outcomes (5.3%), blood group identification (5.3%), blood quality testing (4.5%), and precise blood volume measurement (1.5%). Additionally, 4.5% of the studies were published in journals with an impact factor greater than 10; 19.5% developed software or applications; 31.5% were multi-center studies; 48.1% utilized decision tree methods, while 31.5% employed neural network approaches; and 14.2% conducted external validation of the algorithms. Conclusion: AI demonstrates significant potential in transfusion risk prediction, decision support, and blood management. However, challenges remain, including limited model generalizability, insufficient algorithm interpretability, and barriers to clinical translation. The deep integration of AI with transfusion medicine will accelerate the advent of precision transfusion era, maximizing blood resource utilization, reducing waste, and ensuring transfusion safety.

Objective:To investigate the causal relationships between multiple obesity indices, including body mass index (BMI), body fat percentage, whole-body fat mass, trunk fat mass, leg fat percentage, arm fat percentage, waist circumference, and hip circumference, and preeclampsia (PE) using Mendelian randomization (MR), and to evaluate the mediating effect of triglycerides.Methods:Genome-wide association studies (GWAS) summary statistics from European populations were utilized. Independent genetic loci associated with obesity indices and PE served as instrumental variables of exposure and outcomes. Obesity data (approximately 191 000 female samples) came from UK Biobank; PE data ( n=242 852) from FinnGen Biobank. Causal effects were assessed primarily via inverse variance weighted (IVW), supplemented by MR-Egger, weighted median, MR-pleiotropy residual sum and outlier (MR-PRESSO), and Bayesian weighted MR. Bonferroni correction was applied. Cochran's Q test evaluated heterogeneity; MR-Egger intercept test assessed horizontal pleiotropy; leave-one-out, funnel, and scatter plots conducted sensitivity analyses. Odds ratio ( OR) measured effect sizes. Two-step MR explored triglyceride mediation. Results:Eighty-two to 112 single nucleotide polymorphisms were included as instrumental variables. After Bonferroni correction, significant positive causal associations with PE were observed for: BMI (IVW: OR=1.703, 95% CI: 1.469-1.974, P<0.001), body fat percentage (IVW: OR=1.595, 95% CI: 1.321-1.925, P<0.001), whole-body fat mass (IVW: OR=1.639, 95% CI: 1.389-1.934, P<0.001), right leg fat percentage (IVW: OR=1.610, 95% CI: 1.360-1.905, P<0.001), left leg fat percentage (IVW: OR=1.622, 95% CI: 1.363-1.930, P<0.001), right arm fat percentage (IVW: OR=1.591, 95% CI: 1.351-1.872, P<0.001), left arm fat percentage (IVW: OR=1.710, 95% CI: 1.444-2.024, P<0.001), and waist circumference (IVW: OR=1.815, 95% CI: 1.534-2.148, P<0.001). Sensitivity analyses confirmed robustness. Triglycerides mediated 4.6%-8.2% of these effects. Trunk fat mass and hip circumference showed potential positive associations (IVW: OR>1, 0.005≤ P<0.05). Conclusions:Higher BMI, body fat percentage, whole-body fat mass, leg/arm fat percentages, and waist circumference may increase PE risk, with waist circumference showing the strongest association. These effects may be partially mediated by triglycerides.

Objective:To investigate the clinical effect of indocyanine green angiography (ICGA)-assisted design and harvest of expanded flaps for scar reconstruction.Methods:This study was a retrospective observational study. From April 2019 to August 2023, 19 patients with scars (8 males, 11 females; aged 3-38 years) treated at the Plastic Surgery Hospital of Peking Union Medical College and Chinese Academy of Medical Sciences met the inclusion criteria. The scars were distributed on the head, face, trunk, and extremities. In stage Ⅰ surgery, skin soft tissue expanders were implanted in suitable areas around the scars for skin soft tissue expansion. In stage Ⅱ surgery, the scar tissue was excised, resulting in wound areas ranging from 100 to 210 cm 2, and expanded flaps were designed. ICGA was used to identify target perforators and their accompanying veins, and the flap design was adjusted to ensure the inclusion of complete arterial and venous axes. The expanded flap with an area of 120 to 240 cm2 was harvested using unilateral back-cut technique and transferred to the recipient site, and the donor site wound was sutured directly. The durations of the arterial and venous phases of ICGA during flap design were recorded. The length-to-width ratios of the back-cut flaps were calculated for different regions. After stage Ⅱ surgery, the blood perfusion and survival of the flap, the wound healing at the donor site, and the occurrence of complications were observed. During follow-up, the appearance, color, and texture of the patient's flap were observed. Results:The arterial phase of ICGA lasted 10-27 (18±5) s, and the venous phase lasted 78-116 (100±10) s. The length-to-width ratios of the back-cut flaps were 1.22±0.32, 1.63±0.12, and 1.15±0.21 for the head and neck, trunk, and limb regions, respectively. After stage Ⅱ surgery, one patient had a large area of insufficient blood perfusion in the flap. By comparing ICGA images before and after flap transfer, the sutures at the oral commissure were loosened, the blood flow of the flap was restored. The blood perfusion of the flaps in other patients was good. All flaps survived completely, with well-healed donor site wounds and no complications. During 0.5-14.0 months of follow-up, all flaps of patients demonstrated excellent appearance, with color and texture matching the surrounding skin.Conclusions:As a means of superficial blood flow visualization, ICGA can not only clearly show the microvascular distribution of the expanded flap before operation, assist in optimizing the design of the flap, but also evaluate the blood perfusion of the flap after operation, reduce the occurrence of complications, and provide a full-process navigation for the harvesting of expanded flaps, thereby improving the safety of flap transfer for scar reconstruction.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

A young male patient was diagnosed with aplastic anemia accompanied by paroxysmal nocturnal hemoglobinuria(PNH),and achieved only partial remission after immunosuppressive therapy.Over the past year,his anemia worsened,leading to transfusion dependence,which was considered to be caused by active he-molysis of PNH.Despite switching to eculizumab treatment,his anemia continued to deteriorate.A detailed medical history revealed chronic periodontal infection,with periodontal pain,purulent discharge,and fever in the past month.Multidisciplinary discussion suggested that chronic odontogenic infection activating the comple-ment system was the primary cause of aggravated PNH hemolysis,and the acute infection affected the efficacy of eculizumab.Based on multidisciplinary consultation,a treatment plan was formulated,including intravenous antibiotics combined with periodontal irrigation and tooth extraction to control odontogenic infection,while con-tinuing regular eculizumab infusion.The patient's symptoms improved,hemoglobin levels rose rapidly,and he was no longer transfusion-dependent.This case provides an empirical reference for addressing difficulties en-countered in the treatment of rare diseases with new drugs through multidisciplinary collaborative diagnosis and treatment.