OBJECTIVES: This study aims to explore the association between single nucleotide polymorphisms (SNPs) loci near the haplotype region hg19 chr9:100560865-100660865 of the forkhead box E1 (FOXE1) gene and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P) in western Han Chinese population. METHODS: In the first stage, our study recruited 159 NSCL/P patients and performed targeted region sequencing to screen SNPs loci near the haplotype region of the FOXE1 gene associated with NSCL/P. In the second stage, we selected 21 common SNPs and re-enrolled 1 000 non-syndromic cleft lip only (NSCLO) patients, 1 000 non-syndromic cleft palate only (NSCPO) patients, and 1 000 normal controls to verify the association. PLINK software was used to perform Hardy-Weinberg equilibrium (HWE) test. Association analysis for common variants, gene burden analysis for rare mutations, and function prediction of SNPs with non-synonymous mutations were performed using Mutation Taster and other software programs. RESULTS: In the first stage, 126 variants, including 76 single nucleotide variants and 50 insertion-deletions were identified. All the included SNPs confirmed to HWE, and the results of gene burden analysis and prediction of functional harmfulness for rare variants were not statistically significant. Association analysis showed that rs13292899 of the FOXE1 gene was significantly associated with NSCL/P (P=1.85E-27) and was also correlated with NSCLO (P=6.41E-23) and non-syndromic cleft lip with cleft palate (NSCLP) (P=2.36E-15) subtypes. In the validation phase, rs79268293 (P=0.013, P=0.022), rs10983951 (P=0.009 2, P=0.007 6), rs117227387 (P=0.009 2, P=0.007 6), rs3758250 (P=0.009 2, P=0.007 6), and rs116899397 (P=0.009 2, P=0.007 6) were significantly associated with NSCLO and NSCPO; rs13292899 (P=0.008 5), rs74606599 (P=0.008 3), rs143226042 (P=0.008 3), and rs117236550 (P=0.01) were associated with the occurrence of NSCLO; and rs12343182 (P=0.008 7), rs10119760 (P=0.012), rs10113907 (P=0.012), and rs13299924 (P=0.012) were associated with the occurrence of NSCPO. CONCLUSIONS This study found a new susceptible SNP rs13292899 of the FOXE1 gene that is closely associated with NSCL/P and NSCLO subtype and 13 other SNPs associated with NSCLO or NSCPO.
Female ; Humans ; Male ; China ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Forkhead Transcription Factors/genetics* ; Haplotypes ; Polymorphism, Single Nucleotide ; East Asian People/genetics*

Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine， and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation， and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines， Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome （hereinafter referred to as the Guidelines） were compiled by our research group， in cooperation with the renowned experts in research fields including traditional Chinese medicine， clinical medicine， zoology and evidence-based medicine， which provide a meaningful reference for scientific research， teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place， consensus plays an auxiliary role， and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology， behavioral phenotypic consistency， and drug treatment predictability compared between animal models and human diseases， by the nominal group method， "recommendations" were formed for recommendations supported by evidence， and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types， arthritis modeling methods， external stimulation conditions， and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis， investigation of therapeutic mechanisms， and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.

The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome （hereinafter referred to as the Guidelines） （No. T/CACM1567-2024） was published by Chinese Association of Chinese Medicine on January 11， 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately， and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models， this paper made a declaration of the workflow， technological links， development references， promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To explore the surgical treatment strategies for Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures.Methods:A retrospective analysis was performed on the clinical data of 25 adult patients with Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures, admitted to the Upper Extremity Orthopaedics Department of Zhengzhou Orthopaedic Hospital from June 2013 to June 2023. There were 15 males and 10 females, with an average age of 43.5±14.7 years (range: 20-67 years). Among them, 5 cases were complicated with humeroulnar joint dislocation. The patients were divided into two groups: 17 cases were treated with open reduction and internal fixation (ORIF) of radial head fractures combined with ORIF of proximal ulnar fractures (open reduction group), and 8 cases were treated with radial head replacement combined with ORIF of proximal ulnar fractures (radial head replacement group). At the last follow-up, elbow joint range of motion was recorded, and pain, elbow function, and subjective upper limb function were evaluated using the Visual Analogue Scale (VAS), Mayo Elbow Performance Score (MEPS), and Disabilities of the Arm, Shoulder and Hand (DASH) scale. The incidence of complications was also recorded.Results:All 25 patients were followed up for an average of 25.6±9.0 months (range: 12-45 months). At the last follow-up, the affected elbows in the open reduction group had a flexion of 124.47°±12.59° (range, 90°-140°), extension of 21.12°±10.07° (range, 10°-50°), pronation of 48.59°±11.62° (range, 20°-61°), and supination of 48.53°±8.43° (range, 30°-60°). In the radial head replacement group, the affected elbows showed flexion of 128.75°±13.17° (range, 100°-140°), extension of 14.00°±7.71° (range, 0°-25°), pronation of 61.25°±10.26° (range, 60°-80°), and supination of 71.88°±10.33° (range, 60°-80°). The MEPS score in the open reduction group was 82(75, 85) points (range, 55-90 points), the VAS pain score was 1(1, 2) points (range, 0-3 points), and the DASH score was 9(8, 14) points. In the radial head replacement group, the MEPS score was 90(85, 90) points (range, 85-90 points), the VAS pain score was 1(0, 1) points (range, 0-1 points), and the DASH score was 5(5, 6) points. Complications included 5 cases of heterotopic ossification, 1 case of incision infection, 1 case of nonunion, 1 case of ulnar nerve injury combined with traumatic arthritis, and 1 case of proximal radioulnar bone bridge formation.Conclusions:Both radial head replacement and open reduction internal fixation combined with proximal ulnar fracture fixation can effectively treat Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures. There was no significant difference in postoperative flexion and extension, but the radial head replacement group demonstrated better forearm rotation and DASH scores postoperatively.

Objective:To investigate the effectiveness of gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision in the treatment of chronic Achilles tendon rupture of Myerson type Ⅲ.Methods:A retrospective case series study was conducted to analyze the clinical data of the 18 patients who had been treated at Department of Minimally Invasive Orthopedics, Zhengzhou Orthopaedic Hospital from February 2020 to July 2023 for chronic Achilles tendon rupture of Myerson type Ⅲ by means of gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision. There were 15 males and 3 females, with an age of (37.2±6.8) years. All patients suffered from unilateral injury, involving 13 left sides and 5 right sides. Their body mass index was (22.6±2.5) kg/m 2. The operation time, blood loss, incision length, wound healing and complications were documented. The ankle dorsiflexion and plantar flexion at the last follow-up were compared between the affected side and the healthy side. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Achilles tendon total rupture score (ATRS) before operation were compared with those at the last follow-up. Results:All the 18 patients were followed up for (18.0±5.5) months. Their operation time was (69.1±5.2) minutes, blood loss (71.6±9.2) mL, incision at the broken end of the Achilles tendon (12.4±2.6) cm and incision at the proximal end (2.5±0.4) cm. At the last follow-up, the ankle dorsiflexion was 12.7°±1.9° and the ankle plantar flexion 35.2°±2.0° at the affected side, showing no significant difference from those at the healthy side (13.0°±2.1° and 34.7°±1.8°) ( P>0.05). The AOFAS ankle-hindfoot score was (89.4±3.4) points and the ATRS (85.3±3.2) points for the affected side at the last follow-up, showing significant improvements compared with the preoperative values [(54.2±4.2) points and (51.1±4.6) points] ( P<0.05). All the incisions healed at one stage after operation, with no such complications as incision infection or re-rupture of the Achilles tendon. One patient experienced mild pain at the anchor insertion site, but the pain disappeared 6 months after operation without any treatment. One patient had the symptoms of sural nerve injury which responded to 3 months of oral neurotrophic medication. Conclusion:In the treatment of chronic Achilles tendon rupture of Myerson type Ⅲ, gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision can result in limited invasion, a low incidence of complications, and definite effectiveness.

Objective:To explore the efficacy of a new classification system proposed by us applied to the treatment of irreducible intertrochanteric femoral fractures.Methods:A retrospective study was conducted to analyze the clinical data of the 225 patients with irreducible intertrochanteric femoral fracture who had been treated between January 2023 and November 2024 at Zhengzhou Orthopedic Hospital (78 cases), The First Affiliated Hospital of Zhengzhou University (61 cases), Zhengzhou Central Hospital Affiliated to Zhengzhou University (28 cases), Zhengzhou Hospital of Traditional Chinese Medicine (34 cases), and Puyang Hospital of Traditional Chinese Medicine (24 cases). There were 86 males and 139 females, with an age of (74.8±7.9) years. Satisfactory reduction had failed in all patients even after 3 attempts at closed reduction. The patients were divided into 2 groups based on whether the new classification system proposed by our research team in our previous study was used to guide the treatment. The observation group of 116 cases were treated through an extended incision at the head of the intramedullary nail for reduction and fixation under the guidance of the new classification system while the control group of 109 cases were treated by reduction and fixation through a direct anterolateral incision. The operation time, intraoperative blood loss, fracture healing time, Harris hip scores at 3 months after operation and the last follow-up, and incidence of complications were compared between the 2 groups.Results:No statistically significant differences were observed in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (12.6±2.5) months after operation. The operation time, intraoperative blood loss, and fracture healing time [(39.5±9.7) minutes, (106.6±54.8) mL, and (3.1±0.7) months] in the observation group were significantly less than those in the control group [(70.2±11.1) minutes, (322.8±55.5) mL, and (4.5±0.7) months] ( P<0.05). The Harris hip scores at 3 months after operation and the last follow-up in the observation group [(90.3±3.4) points and (93.7±3.2) points] were significantly higher than those in the control group [(75.1±3.8) points and (78.7±3.6) points] ( P<0.05). The incidence of complications in the observation group was 6.0% (7/116), significantly lower than that in the control group [14.7% (16/109)] ( P<0.05). Conclusion:In the treatment of irreducible intertrochanteric femoral fractures, compared with the conventional anterolateral approach for intramedullary nailing, the extended intramedullary head nail approach guided by our new classification system can reduce operation time, intraoperative blood loss, fracture healing time, and incidence of postoperative complications, and improve postoperative hip joint function.

Objective To study the carrier rate and mutation spectrum of thalassemia genes in the population in Dehong Prefecture,Yunnan Province,thereby providing a scientific basis for developing precise thalassemia prevention and control strategies in this region.Methods A total of 6946 samples were screened and diagnosed for α-thalassemia and β-thalassemia using genetic screening and diagnostic techniques.The carrier status of thalassemia genes in the population was statistically analyzed.Results Among the 6946 samples,1880 tested positive for thalassemia genes,yielding a positive rate of 27.07%(1880/6946).This study detected 1174 α-thalassemia positive samples,with a positive rate of 16.90%(1174/6946).Among the mutation types,-α3.7/αα was identified as the predominant genotype.There were 493 β-thalassemia positive samples,with a positive rate of 7.10%(493/6946).Among the mutation types,CD26 was the most predominant mutation type.The differences in carrier rates between α-thalassemia and β-thalassemia was statistically significant(P<0.01).Additionally,213 samples were positive for both α-thalassemia and β-thalassemia(compound carriers),with a positive rate of 3.07%(213/6946).There were also 207 intermediate thalassemia positive samples,with a positive rate of 2.98%(207/6946).Among these,the-α3.7/--SEA genotype was the most predominant.Conclusion Dehong region is a high-prevalence area for thalassemia carriers,with a relatively high positive rate for thalassemia.The most common gene mutation type was-α3.7/αα and CD26.

Objective:To explore the surgical treatment strategies for Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures.Methods:A retrospective analysis was performed on the clinical data of 25 adult patients with Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures, admitted to the Upper Extremity Orthopaedics Department of Zhengzhou Orthopaedic Hospital from June 2013 to June 2023. There were 15 males and 10 females, with an average age of 43.5±14.7 years (range: 20-67 years). Among them, 5 cases were complicated with humeroulnar joint dislocation. The patients were divided into two groups: 17 cases were treated with open reduction and internal fixation (ORIF) of radial head fractures combined with ORIF of proximal ulnar fractures (open reduction group), and 8 cases were treated with radial head replacement combined with ORIF of proximal ulnar fractures (radial head replacement group). At the last follow-up, elbow joint range of motion was recorded, and pain, elbow function, and subjective upper limb function were evaluated using the Visual Analogue Scale (VAS), Mayo Elbow Performance Score (MEPS), and Disabilities of the Arm, Shoulder and Hand (DASH) scale. The incidence of complications was also recorded.Results:All 25 patients were followed up for an average of 25.6±9.0 months (range: 12-45 months). At the last follow-up, the affected elbows in the open reduction group had a flexion of 124.47°±12.59° (range, 90°-140°), extension of 21.12°±10.07° (range, 10°-50°), pronation of 48.59°±11.62° (range, 20°-61°), and supination of 48.53°±8.43° (range, 30°-60°). In the radial head replacement group, the affected elbows showed flexion of 128.75°±13.17° (range, 100°-140°), extension of 14.00°±7.71° (range, 0°-25°), pronation of 61.25°±10.26° (range, 60°-80°), and supination of 71.88°±10.33° (range, 60°-80°). The MEPS score in the open reduction group was 82(75, 85) points (range, 55-90 points), the VAS pain score was 1(1, 2) points (range, 0-3 points), and the DASH score was 9(8, 14) points. In the radial head replacement group, the MEPS score was 90(85, 90) points (range, 85-90 points), the VAS pain score was 1(0, 1) points (range, 0-1 points), and the DASH score was 5(5, 6) points. Complications included 5 cases of heterotopic ossification, 1 case of incision infection, 1 case of nonunion, 1 case of ulnar nerve injury combined with traumatic arthritis, and 1 case of proximal radioulnar bone bridge formation.Conclusions:Both radial head replacement and open reduction internal fixation combined with proximal ulnar fracture fixation can effectively treat Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures. There was no significant difference in postoperative flexion and extension, but the radial head replacement group demonstrated better forearm rotation and DASH scores postoperatively.

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.