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.

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

Objective:To explore the genetic etiology of a pedigree with intellectual disability and explore its pathogenesis.Methods:A Chinese pedigree which had presented at the Henan Provincial People′s Hospital in March 2023 was selected as the study subject. Clinical data of the pedigree were collected, along with peripheral venous blood samples from its members. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Amniotic fluid was collected for prenatal diagnosis. This study was approved by the Medical Ethics Committee of the Henan Provincial People′s Hospital (No. 2019-134).Results:Both the proband (a 6-year-old male) and his mother (30 years old) had various degrees of intellectual and motor impairment. WES revealed that the proband has harbored a de novo heterozygous c. 2563_2567dup (p.Lys856fs) variant of the UBE3A gene, while his mother, maternal grandmother and fetus had all harbored a novel heterozygous c. 409+ 1G>A variant of the RNF13 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+ PS1+ PM2_Supporting; PVS1+ PM2_Supporting+ PP3). Conclusion:Based on the clinical manifestations and the result of genetic testing, the heterozygous c.2563_2567dup (p.Lys856fs) variant of the UBE3A gene probably underlay the intellectual disability and developmental delay in the proband, whilst the heterozygous c. 409+ 1G>A variant of the RNF13 gene may underlie the intellectual disability in the proband′s mother and grandmother. Above results have enabled genetic counseling and prenatal diagnosis for this pedigree.

The establishment of a traceability system for the entire industry chain of Chinese medicinal materials can enhance regional brand building,raise the quality awareness of medicinal material producers,standardize the production processes of Chinese medicinal materials,and ensure the production of high-quality medicinal materials.Sichuan Province has successfully implemented a provincial-level Traditional Chinese Medicine(TCM)tracing system that is interconnected across provinces,cities,and counties.This system enables the complete tracking of the entire supply chain,starting from seed and seedling cultivation,through planting and breeding,harvesting and processing,and finally to the production and distribution of decoction pieces in trade and medical institutions.This research provides a comprehensive overview of the progress made in establishing the Chinese herbal medicine traceability system in Sichuan Province.It analyzes the existing challenges faced by participating enterprises,such as the hierarchy of involvement,information integrity,and the overall impact of the system.Moreover,the paper presents valuable insights and suggestions for the further development of the Chinese herbal medicine traceability system in Sichuan Province.These recommendations focus on enhancing the traceability scope,improving service capabilities,promoting data sharing,and establishing standardized norms and guidelines.

Objective:A novel anatomic posterior malleolus locking plate for Chinese people was designed, researched, developed, and tested biomechanically.Methods:An anatomic parameter database of posterior malleolus of Chinese people was established by collecting CT images of ankle joints from 100 healthy volunteers in Shanghai Tongji hospital from June 2022 to May 2023. Combined with relevant computer-aided technologies, a novel anatomic posterior malleolus locking plate for Chinese people was designed and produced. In addition, model verification and biomechanical test were carried out on vertical displacements under different fixation modes and different axial loads (500, 1 000, and 1 500 N). Failure loads at a displacement of 2 mm and maximum failure loads at the complete failure of internal fixation were also tested and recorded.Results:Based on the imaging anatomic measurement, the width quartile of posterior malleolus was 19.4, 26.6, 35.0 mm. The 3D reconstruction models of ankle joint CT corresponded to small, medium, and large basic posterior malleolus plates. Height of the screw safety zone was 5.5(5.3, 5.7) mm. The tip-back angle was 153.0°(148.5°, 157.5°) and tip-back height was 20.0(19.7, 20.9) mm. The novel anatomic posterior malleolus locking plate based on tibiofibular and ankle joint CT scan and relevant computer-aided technologies fit well with posterior malleolus of tibia, showing anatomic fitting. Based on the associate biomechanical test, the novel plate fixation had smaller vertical displacements of posterior malleolus fragment under axial loads of 500, 1 000, and 1 500 N compared with the control plate, but greater failure loads when the vertical displacement of the posterior malleolus fragment was 2 mm and greater maximum failure loads at complete failure of the internal fixation. At an axial load of 500 N, the vertical displacements of the posterior malleolus fragment after posterior malleolus fixation with a control plate, a 6-hole anatomical locking plate, and a 5-hole anatomical locking plate were 0.60±0.02, 0.45±0.04, and 0.52±0.04 mm, respectively with significant difference ( F=88.287, P<0.001); at an axial load of 1 000 N, the vertical displacements were 2.22±0.03, 1.10±0.03, and 1.15±0.03 mm for the three fixation modes, respectively, and the difference was statistically significant ( F=10 061.890, P<0.001); At an axial load of 1 500 N, the vertical displacements were 2.81±0.04, 1.50±0.03 and 1.67±0.03 mm for the three fixation modes, respectively with significant difference ( F=9 774.019, P<0.001). When the vertical displacement of the posterior malleolus fragment was 2 mm, the failure loads for the three fixation modes were 0.80(0.73, 0.80)、2.00(1.93, 2.00) and 1.70(1.70, 1.70) kN, respectively with significant differences ( H=54.245, P<0.001). The maximum failure loads at complete failure of the internal fixation for the three fixation modes were 1.90(1.90, 1.98)、4.30(4.30, 4.30) and 3.70(3.63, 3.70) kN, respectively with significant differences ( H=53.863, P<0.001). Conclusions:The novel anatomic posterior malleolus locking plate for Chinese people was well matched to the posterior malleolus with high mechanical strength and good stability, showing a promising future for clinical application.

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ²=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
Female ; Humans ; Adult ; Medroxyprogesterone Acetate/adverse effects* ; Endometrial Hyperplasia/pathology* ; Dydrogesterone/adverse effects* ; Hyperplasia ; Prospective Studies

Objective:To assess the ultrasonographic features and potential diseases of fetal abnormal sylvian fissure(SF), and to explore the value of whole-genome sequencing (WGS) in prenatal detection.Methods:A total of 28 fetuses with a sonographic diagnosis of abnormal SF in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University between October 2018 and October 2020 were prospectively included. The fetal brain was evaluated by neuroultrasound and intrauterine MRI in detail. Amniotic fluid/cord blood obtained by amniocentesis or tissue samples from umbilical cord after birth were collected for WGS. Pregnancy outcomes and postnatal MRI were recorded, and neurodevelopment of live-born infants was followed up for more than 24 months after delivery.Results:During the study period, 28 fetuses with abnormal SF were identified, with a gestational age of 21.3-30.0 (24.8±2.0) weeks. Abnormal SF presented in MCD ( n=15, 53.6%), chromosomal anomalies ( n=3, 10.7%) or single-gene genetic syndromes ( n=3, 10.7%) with the affected fetuses showing developmental delay, hydrocephalus or leukomalacia ( n=4, 14.2%), corpus callosal agenesis with large interhemispheric cysts ( n=1, 3.6%), benign subarachnoid space enlargement with arachnoid cysts ( n=1, 3.6%), and multiple malformations ( n=1, 3.6%). Among the 15 cases with MCD, the most common pathology was lissencephaly/pachygyria, followed by schizencephaly, severe microcephaly, hemimegalencephaly with paraventricular heterotopia, and polymicrogyria. Abnormal SF presented bilaterally in 23 fetuses and unilaterally in 5. All cases were categorized into six types depending on SF morphology in the transthalamic section: no plateau-like or a small insula, linear type, irregular corrugated SF, Z-shaped, and cyst occupying type. In addition to abnormal SF, associated anomalies or mild variations were identified in all fetuses. There were 17 cases underwent intrauterine MRI, and 13 cases underwent postnatal MRI examination.And 25 pregnancies were terminated; 3 were born alive, and 2 had typical syndromic changes with poor neurodevelopmental prognosis. A related pathogenic genetic variant was detected in 57.1% (16/28) fetus, and the incidence of single nucleotide variants(SNVs) was 42.9% (12/28), among which de novo SNVs accounted for 91.7% (11/12). Conclusions:Fetal abnormal SF could be classified based on the ultrasonographic features of transthalamic section. Fetal abnormal SF may indicate MCD, some chromosomal abnormalities or single-gene genetic syndromes that may lead to poor neurodevelopmental outcomes, and may be affected by extra-cortical factors. It is suggested to carry out targeted prenatal genetic diagnosis for fetuses with abnormal SF.

Objective:To summarize and analyze the current application status of oral mucosal graft (OMG) technique in the repair of ureteral strictures in China, and clarify the feasibility, safety and effectiveness of this technique.Methods:The 175 patients who underwent repair of ureteral stricture using oral mucosal patches from June 2015 to February 2022 were etrospectively analyzed in 14 medical centers in China, including 49 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 32 cases in Affiliated Seventh Medical Center of PLA General Hospital, 3 cases in The Second Hospital of Anhui Medical University, 6 cases in The First Affiliated Hospital of Zhengzhou University, 56 cases in Peking University First Hospital, 3 cases in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 cases in Shanghai Sixth People' s Hospital, 4 cases in General Hospital of Estern Theater Command, 4 cases in Lanzhou University Second Hospital, 2 cases in Guizhou Province People 's Hospital, 2 cases in Peking University People' s Hospital, 5 cases in Jinzhou First People's Hospital, 5 cases in The First Affiliated Hospital of Wannan Medical College, 1 case in Shandong Provincial Hospital. In this study, 127 patients (72.6%) used lingual mucosal patches, 32(18.3%) labial mucosa, and 16(9.1%) buccal mucosa. The surgical approach for OMG ureteral reconstruction was mainly minimally invasive, with robot-assisted laparoscopy in 84 patients (48.0%), traditional laparoscopic surgery in 87 patients (49.7%), and open surgery in only 4 patients (2.3%). There were 133 males and 42 females with an average age of (35.0±17.2) years. The mean body mass index (BMI) and stenosis length were (23.1±4.1) kg/m 2 and (4.7±1.8) cm, respectively. The stricture was located in the left ureter in 116 patients, right ureter in 58 case and bilateral ureter in 1 case. The most common causes of ureteral stricture were endoscopic surgery in 88(50.3%)patients, congenital stricture in 55(31.4%)patients, failed ureteroplasty in 29(16.6%)patients, history of extracorporeal shock wave lithotripsy in 13(7.4%)patients, radiotherapy history in 3(1.7%)patients and other causes in 6(3.4%)patients. Strictures were mainly located in the upper ureter, accounting for 61.7% (108/175 cases), followed by 36.0% (63/175) at the ureteropelvic junction and 2.3%(4/175)in the middle ureter. According to the surgical methods, the patients were divided into robot-assisted laparoscopic surgery group ( n=84), traditional laparoscopic surgery group ( n=87)and open surgery group ( n=4). Subgroup analysis of patients in robot-assisted laparoscopic and traditional laparoscopic surgery groups was performed. There were no significant difference in preoperative data between the two groups except for age (32.0±18.3) years vs.(37.0±15.9)years, P=0.040], BMI[(22.5±4.3)kg/m 2 vs. (23.7±3.6)kg/m 2, P=0.028], and etiology of stenosis [endoscopic injury, 34(40.5%) vs. 53(60.9%), P=0.012]. Preoperative hydronephrosis and stricture length were assessed by CTU and ureterography. Ureterography 7-9 weeks after surgery showed patency of the reconstructed segment, or no recurrence of hydronephrosis was judged as success. Evaluate the operation method, operation time, success rate, length of OMG in repairing ureteral stricture between laparoscopic and robot-assisted groups. Results:The overall success rate of oral mucosal graft repair surgery reached 97.7%(171/175). The success rate of ureteral reconstruction in the two groups were 96.4%(81/84)and 98.9%(86/87), respectively ( P=0.351), and the difference was not statistically significant. There was no significant difference for operation time, intraoperative blood loss, and mean oral mucosal length between the robotic and laparoscopic groups[(244.7±85.8) min and (222.7±83.5)min ( P=0.116), (58.9±38.6) ml and (68.4±45.5) ml ( P=0.217), (5.0±2.0) cm and (4.6±1.5) cm ( P=0.350)], respectively.Postoperative complications were reported in 23 (13.1%) patients, such as fever, urinary leakage, lymphatic leakage, infection, but only 2 (1.4%) cases patients had complications of Clavien-Dindo score ≥ Ⅲ. The two patients developed urinary stricture after surgery with failed conservative treatment, and no urinary stricture occurred following endoscopic treatment.The short-term (three months after surgery)incidence of complications in the site where the oral mucosa was taken, such as difficulty in opening mouth, pain, and swelling, was 12.0% (21/175), and there was no significant difference for oral complications between patients harvesting different length of mucosal graft. Conclusions:Ureteroplasty with oral mucosal graft is a safe, feasible and reliable technique for ureteral reconstruction. At present, minimally invasive technology is the main surgical approach for ureteroplasty, and there is no significant difference in operation time and success rate between robotic surgery and laparoscopic surgery.

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation. Please cite this article as: Jiang LH, Li PJ, Wang YQ, Jiang ML, Han XY, Bao YD, Deng XL, Wu WB, Liu XD. Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease. J Integr Med. 2023; 21(6): 518-527.
Animals ; NF-kappa B/metabolism* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Acupuncture Therapy ; Cytokines ; Disease Models, Animal ; Inflammation/therapy*

AIM: To elucidate the relationship between childhood asthma susceptibility and clinical efficacy of inhaled glucocorticoids (ICS) in children with different genotypes of asthma by exploring rs776746 and rs15524 single nucleotide polymorphisms (SNPs) of cytochrome P450 enzyme 3A5 (CYP3A5) gene in asthmatic children and healthy children. METHODS: The CYP3A5 gene rs776746 and rs15524 polymorphic sites were detected in 79 children (Case group) with asthma of Han nationality and 100 healthy children (Control group) who met the inclusion criteria admitted to the Northern Theater General Hospital in Northeast China from October 2016 to October 2020, and genotype, allele and linkage analysis were performed. The case group was given inhaled glucocorticoids by nebulised inhalation for 3 months, and lung function and exhaled breath nitric oxide (FeNO) were measured at entry and after treatment, and asthma control score C-ACT/ACT was done after treatment, so as to compare the prevalence of different genotypes and the differences in the above test index scores. RESULTS: There was complete linkage disequilibrium at rs776746 and rs15524 loci. There were three genotypes of T/T, T/C and C/C at rs776746 locus of CYP3A5 gene. There were significant differences in the frequency of different genotypes between the case group and the control group (χ