ObjectiveTo retrospectively analyze the epidemiological trends of birth defects in perinatal infants in Fengxian District, Shanghai from 2018 to 2022, so as to provide a scientific evidence for the formulation of related prevention and control strategies. MethodsBased on the data from the National Birth Defects Surveillance System, statistical analysis was conducted on the perinatal birth defects from monitored hospitals within the region from 2018 to 2022. ResultsFrom 2018 to 2022, a total of 20 870 perinatal infants delivered in the monitored hospitals in Fengxian District, with 472 cases with birth defects, showing a significant increase in the prevalence of birth defects (PRR=1.49, 95%CI: 1.39‒1.59). The risk of birth defects increased with maternal age, especially for advanced maternal age (PRR=1.58, 95%CI: 1.12‒2.25). Infants born to mothers with gestational diabetes had a higher prevalence of birth defects compared to those without gestational diabetes (PRR=1.99, 95%CI: 1.46‒2.70). Infants with birth defects were more likely to be born prematurely (PRR=2.07, 95%CI:1.56‒2.76). The top three types of birth defects were congenital heart disease (CHD), other anomalies of the external ear, and polydactyly. ConclusionThe prevalence of birth defects in Fengxian District monitored hospitals showed an upward trend from 2018 to 2022. Advanced maternal age and gestational diabetes were identified as risk factors for birth defects. CHD is the leading type of birth defect in Fengxian District over the five-year period. To reduce the prevalence of birth defects, it is crucial to implement comprehensive prevention and treatment measures for CHD.

OBJECTIVE: To evaluate the effectiveness of functional perforator flaps utilizing the superficial circumflex iliac artery as a vascular pedicle, as well as chimeric iliac bone flaps, in the reconstruction of composite tissue defects in the hand and foot. METHODS: A retrospective review of the clinical data from 13 patients suffering from severe hand or foot injuries, treated between May 2019 and January 2025, was conducted. The cohort comprised 8 males and 5 females, with ages ranging from 31 to 67 years (mean, 48.5 years). The injuries caused by mechanical crush incidents (n=9) and traffic accidents (n=4). The distribution of injury sites included 8 cases involving the hand and 5 cases involving the foot. Preoperatively, all patients exhibited bone defects ranging from 2.0 to 6.5 cm and soft tissue defects ranging from 10 to 210 cm². Reconstruction was performed using functional perforator flaps based on the superficial circumflex iliac artery and chimeric iliac bone flaps. The size of iliac bone flaps ranged from 2.5 cm×1.0 cm×1.0 cm to 7.0 cm×2.0 cm×1.5 cm, while the size of the soft tissue flaps ranged from 4 cm×3 cm to 15 cm×8 cm. In 1 case with a significant hand defect, a posterior interosseous artery perforator flap measuring 10.0 cm×4.5 cm was utilized as an adjunct. Likewise, an anterolateral thigh perforator flap measuring 25 cm×7 cm was combined in 1 case involving a foot defect. All donor sites were primarily closed. Postoperative flap survival was monitored, and bone healing was evaluated through imaging examination. Functional outcomes were assessed based on the location of the defects: for hand injuries, grip strength, pinch strength, and flap two-point discrimination were measured; for foot injuries, the American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analogue scale (VAS) score, Maryland Foot Score, plantar pressure distribution and gait symmetry index (GSI) were evaluated. RESULTS: All flaps survived completely, with primary healing observed at both donor and recipient sites. All patients were followed up 6-18 months (mean, 12.2 months). No significant flap swelling or deformity was observed. Imaging examination showed a bone callus crossing rate of 92.3% (12/13) at 3 months after operation, and bone density recovered to more than 80% of the healthy side at 6 months. The time required for bone flap integration ranged from 2 to 6 months (mean, 3.2 months). One patient with a foot injury exhibited hypertrophic scarring at the donor site; however, no major complication, such as infection or bone nonunion, was noted. At 6 months after operation, grip strength in 8 patients involving the hand recovered to 75%-90% of the healthy side (mean, 83.2%), while pinch strength recovered to 70%-85% (mean, 80%). Flap two-point discrimination ranged from 8 to 12 mm, approaching the sensory capacity of the healthy side (5-8 mm). Among the 5 patients involving the foot, the AOFAS score at 8 months was 80.5±7.3, VAS score was 5.2±1.6. According to the Maryland Foot Score, 2 cases were rated as excellent and 3 as good. Gait analysis at 6 months after operation showed GSI above 90%, with plantar pressure distribution closely resembling that of the contralateral foot. CONCLUSION The use of functional perforator flaps based on the superficial circumflex iliac artery, combined with chimeric iliac bone flaps, provides a reliable vascular supply and effective functional restoration for the simultaneous repair of composite bone and soft tissue defects in the hand or foot. This technique represents a viable and effective reconstructive option for composite tissue defects in these anatomical regions.
Humans ; Male ; Middle Aged ; Female ; Perforator Flap/transplantation* ; Adult ; Plastic Surgery Procedures/methods* ; Hand Injuries/surgery* ; Aged ; Retrospective Studies ; Foot Injuries/surgery* ; Ilium/transplantation* ; Iliac Artery/surgery* ; Soft Tissue Injuries/surgery* ; Bone Transplantation/methods* ; Treatment Outcome

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Objective:To investigate the clinical effect of anterolateral thigh perforator flap (ALTPF) combined with transfer of fascia lata in reconstruction of complex tissue defects of hand and foot.Methods:From July 2021 to October 2023, 9 patients with complex tissue defects of hand and foot were treated with ALTPF combined with fascia lata in the Department of Orthopaedic Microsurgical Repair and Reconstruction of Fuyang People's Hospital Affiliated to Anhui Medical University. There were 2 males and 7 females with an average age of 28.1 (range, 4-65) years old. Three patients had extensor tendon defects in 6 digits of dorsal hands, 5 had extensor tendon defect in 10 toes of dorsal foot, 1 had a defect of anterior tibial tendon and 1 had Achilles tendon defect in posterior ankles. The sizes of soft tissue defect ranged from 8.0 cm×6.0 cm to 15.0 cm×10.0 cm, and the lengths of tendon defect ranged from 6.0 to 13.0 cm. Preoperative Doppler ultrasound was used to locate the distribution of perforating branches in the anterolateral thigh region. According to the characteristics of wound, ALTPFs and fascia lata were designed and harvested. Fascia lata with an appropriate size of 1.5 cm×8.0 cm-4.5 cm×15.0 cm were taken to bridge the defects of the tendon and the Achilles tendon. The wounds were reconstructed with flaps sized 9.0 cm×6.5 cm-18.0 cm×7.5 cm. Nine fascia lata donor sites and 8 flap donor sites were sutured directly. One donor site was treated with a skin graft of ipsilateral ilioinguinal region. The survival and complications of the flaps and donor sites were observed through outpatient follow-up visits, WeChat reviews and home visits, etc. The hand function was assessed according to the Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association, and the foot and ankle function was assessed according to the Mazur score standard of joint range of motion and motor function.Results:All patients were included in follow-up for 4-24 (mean, 13.4) months with complete clinical data being collected. All 9 ALTPFs survived and healed primarily. A linear scar left in donor sites in 8 patients, and mild lamellar scar at skin graft in 1 patient. Texture and colour of the flaps were similar to the surrounding tissue without secondary flap thinning surgery. Combined with postoperative rehabilitation training, satisfactory function recoveries were achieved. Hand function of 3 patients were evaluated according to Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association, 2 patients were excellent and 1 was good. Ankle and foot functions in 6 patients were evaluated according to the range of motion of ankle and foot and Mazur score standard for motor function, 4 patients were excellent and 2 were good.Conclusion:ALTPF combined with fascia lata transfer can reconstruct the complex tissue defects of hand and foot. Of which, 1 donor site can meet the requirements of 2 types of tissues reconstruction at the same time, and with minimal damage to the donor site as well as an precise reconstruction of the recipient site. It avoids staged surgery, shortens the treatment time and reduces the cost of treatment.

Objective: To explore the pathogenic genes in a Chinese family affected by nonsyndromic tooth agenesis so as to study the pathogenesis of oligodontia. Methods : Hospital ethical approval and informed consent of the patients and family members were obtained. Clinical data of the proband and close family members were collected, peripheral venous blood was collected, and DNA was extracted. Gene sequencing was performed through whole-exome sequencing, and then the screened pathogenic genes were verified by Sanger sequencing. The three-dimensional structure of the mutant proteins was analyzed and compared with the wild-type using bioinformatics tools. Results: The two patients with congenital majority tooth loss in this family were cousins, and there were no other patients with congenital majority tooth loss in the family. Besides congenital multiple tooth loss, the two patients had no obvious hair abnormalities, finger/toe abnormalities, sweating abnormalities or other abnormal manifestations of ectodermal tissue. We found a mutant gene that in this family by carrying out gene sequencing of the patients and their close family members. A novel EDA (ectodysplasin A) missense mutation c.983C>T (p. Pro328Leu) was identified, which changed the encoded amino acid from proline (Pro) to leucine (Leu). Analysis of the mutation site showed that the site was highly conserved, and three-dimensional structure modeling also found that it changed the structure of EDA. Conclusion A novel EDA missense variant (c.983C>T, p.Pro328Leu) was first identified in a Chinese family with nonsyndromic tooth agenesis, extending the mutation spectrum of the EDA gene.

Ethical review runs through the whole process of drug clinical trials, and is a critical step to ensure the rights and interests of subjects. This paper analyzed and discussed the role and positioning of ethical review in new drug clinical trials, cleared the principles of ethical review, identified the responsibilities of ethical review, and clarified the authority of ethical review approval documents. The ethical review should primarily focus on the ethics of the clinical trials, not replace other professional institutions to review the clinical trials’ legality and scientific nature. Ethical approval is only one of the necessary conditions for conducting clinical trials, not the only factor. It is recommended to strengthen the publicity and popularization of scientific and technological ethics awareness, improve the clinical trial approval mechanism, and optimize the phrasing of ethical review approval documents. It is warranted to further optimize the quality of ethical review, improve the construction of ethical review system, ultimately achieve the unity of promoting innovation and preventing risks, so as to effectively realize the benign interaction between high-quality development of scientific and technological innovation and high-level safety.

To explore the differentially expressed genes (DEGs) related to biosynthesis of active ingredients in wolfberry fruits of different varieties of Lycium barbarum L. and reveal the molecular mechanism of the differences of active ingredients, we utilized Illumina NovaSeq 6000 high-throughput sequencing technology to conduct transcriptome sequencing on the fruits of 'Ningqi No.1' and 'Ningqi No.7' during the green fruit stage, color turning stage and maturity stage. Subsequently, we compared the profiles of related gene expression in the fruits of the two varieties at different development stages. The results showed that a total of 811 818 178 clean reads were obtained, resulting in 121.76 Gb of valid data. There were 2 827, 2 552 and 2 311 DEGs obtained during the green fruit stage, color turning stage and maturity stage of 'Ningqi No. 1' and 'Ningqi No. 7', respectively, among which 2 153, 2 050 and 1 825 genes were annotated in six databases, including gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and clusters of orthologous groups of proteins (KOG). In GO database, 1 307, 865 and 624 DEGs of green fruit stage, color turning stage and maturity stage were found to be enriched in biological processes, cell components and molecular functions, respectively. In the KEGG database, the DEGs at three developmental stages were mainly concentrated in metabolic pathways, biosynthesis of secondary metabolites and plant-pathogen interaction. In KOG database, 1 775, 1 751 and 1 541 DEGs were annotated at three developmental stages, respectively. Searching the annotated genes against the PubMed database revealed 18, 26 and 24 DEGs related to the synthesis of active ingredients were mined at the green fruit stage, color turning stage and maturity stage, respectively. These genes are involved in carotenoid, flavonoid, terpenoid, alkaloid, vitamin metabolic pathways, etc. Seven DEGs were verified by RT-qPCR, which showed consistent results with transcriptome sequencing. This study provides preliminary evidences for the differences in the content of active ingredients in different Lycium barbarum L. varieties from the transcriptional level. These evidences may facilitate further exploring the key genes for active ingredients biosynthesis in Lycium barbarum L. and analyzing their expression regulation mechanism.
Flavonoids/metabolism* ; Fruit/genetics* ; Gene Expression Profiling/methods* ; Gene Expression Regulation, Plant ; Lycium/metabolism* ; Metabolic Networks and Pathways ; Transcriptome

Objective:To analyze the diagnostic value of cell-free plasma metagenomic next-generation sequencing (mNGS) pathogen identification for severe aplastic anemia (SAA) bloodstream infection.Methods:From February 2021 to February 2022, mNGS and conventional detection methods (blood culture, etc.) were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection, as well as the impact on clinical treatment benefits and clinical accuracy.Results:①Among the 33 samples evaluated by mNGS and conventional detection methods, 25 cases (75.76%) carried potential pathogenic microorganisms. A total of 72 pathogenic microorganisms were identified from all cases, of which 65 (90.28%) were detected only by mNGS. ②All 33 cases were evaluated for diagnostic consistency, of which 2 cases (6.06%) were Composite, 18 cases (54.55%) were mNGS only, 2 cases (6.06%) were Conventional method only, 1 case (3.03%) was both common compliances (mNGS/Conventional testing) , and 10 cases (30.3%) were completely non-conforming (None) . ③All 33 cases were evaluated for clinical treatment benefit. Among them, 8 cases (24.24%) received Initiation of targeted treatment, 1 case (3.03%) received Treatment de-escalation, 13 cases (39.39%) received Confirmation, and the remaining 11 cases (33.33%) received No clinical benefit. ④ The sensitivity of 80.77%, specificity of 70.00%, positive predictive value of 63.64%, negative predictive value of 84.85%, positive likelihood ratio of 2.692, and negative likelihood ratio of 0.275 distinguished mNGS from conventional detection methods (21/12 vs 5/28, P<0.001) . Conclusion:mNGS can not only contribute to accurately diagnosing bloodstream infection in patients with aplastic anemia, but can also help to guide accurate anti-infection treatment, and the clinical accuracy is high.

Background Non-occupational carbon monoxide (CO) poisoning is a public health problem that seriously affect people’s health and lives. Objective To describe the prevalence of non-occupational CO poisoning during 2007—2018 in Shanghai, analyze its epidemiological characteristics and potential influencing factors, and explore effective prevention and control measures. Methods Daily reported non-occupational CO poisoning cases and meteorological factors from 2007 to 2018 were collected in Shanghai, epidemiological characteristics were analyzed by descriptive epidemiology methods, and a distributed lag nonlinear model was used to assess the association between temperature and non-occupational CO poisoning. Results A total of 2264 non-occupational CO poisoning events and 3866 cases from 2007 to 2018 were reported in Shanghai, including 59 death cases. More than half of the poisoning cases were female (56.3%), and young adults accounted for more cases than any other age group (54.8%). The poisoning events mainly occurred in winter (from December to next February); however, cases reported in summer increased in recent years. The peak period of the events was from 20:00 to 24:00. Households (85.2%) and restaurants (8.0%) were the common places of non-occupational CO poisoning events, and the main cause was improper use of gas water heater (36.9%). A nonlinear curve was found between daily average temperature of current day and the occurrence of non-occupational CO poisoning. Temperature was negatively associated with the risk of non-occupational CO poisoning when the temperature was lower than 9.6 ℃, while a positive association was found during 9.7-26.0 ℃. Conclusion Winter is a high season for non-occupational CO poisoning in Shanghai, rising cases reported in summer is also worthy of attention. Supervision should be strengthened to ban sales of unqualified gas water heaters, and health education on CO poisoning prevention and control should be conducted through multiple channels, in order to reduce the incidence of CO poisoning.

With the implementation of the national biomedical innovation strategy, new requirements for ethical review of clinical trials have been put forward, and more attention has been paid to the ethical pre-review. Based on the current situation of clinical trials and ethical review of new drugs in China, this paper discussed the concept, advantages and necessity of ethical pre-review, sorted out the problems and challenges in the implementation of ethical pre-review at this stage, and put forward the following suggestions on how to better implement ethical pre-review in clinical trials under the pharmaceutical innovation strategy: the complete definition of "ethical pre-review" should be made clearly; ethical review should be carried out on the basis of necessary reference; the scope of application of ethical pre-review should be clarified; after the ethical pre-review, the statement of the approval document should be standardized and accurate.