Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To analyze the clinical characteristics of IgG4-related disease (IgG4-RD),guide the selection of therapeutic drugs,and to explore the significance of potential tumor identification for IgG4-RD.Methods A total of 92 patients diagnosed with IgG4-RD and admitted to this hospital from January 1,2017 to December 31,2021were selected as the research subjects by using the Yidu Cloud system.The clinical data conducted the summary analysis. The clinical characteristics of IgG4-RD were summarized.Results The mean age of IgG4-RD was definitely diagnosed in the 92 patients was (58.1±11.3)years old,with 65 male ca-ses (70.7％) and 27 female cases (29.3％).The most commonly affected organ tissues were lymph nodes (37 cases,40.2％),pancreas (33 cases,35.9％) and salivary glands (31 cases,33.7％).In the patients woth the 92 patients,28 cases (30.4％) had involvement of a single organ tissue,while 32 cases (34.8％) had involvement of two or more organs.In the 92 patients,89 cases received steroid therapy,and 71 cases received immunosup-pressive therapy,in which 45 cases (63.4％) used cyclophosphamide.The initial treatment effective rate (72.7％ vs. 55.6％) and one-year non-recurrence rate (38.2％ vs. 20.0％) of the steroid combined immuno-suppressive therapy group were better than those of the single steroid group,but the differences were not sta-tistically significant (P>0.05).The proportion of the patients with tumor comorbidity and IgG4 level>40 g/L (18.2％) was significantly higher than that of the non-tumor comorbidity (1.2％),and the difference was statistically significant (P<0.05).However,there was no statistically significant difference in the proportion of patients with tumor comorbidity compared to the non-tumor comorbidity in other IgG4 level groups (P>0.05).Conclusion IgG4-RD is more common in middle-aged and elderly men,lymph nodes,pancreas and sal-ivary glands are commonly involved,and most patients have the double organs and multiple organs involve-ment. The combination use of hormone and immunosuppressant in treatment is recommended .The IgG4 lev-el>40 g/L in the patients with IgG4-RD may has the suggestive significance for complicating tumor.

Objective:To investigate whether silencing information regulator 1 (SIRT1) activation can relieve paclitaxel-induced neuropathic pain by inhibiting mitochondrial damage in dorsal root ganglion neurons.Methods:Forty-eight healthy male SD rats were randomly divided into solvent control group, paclitaxel group, paclitaxel+SIRT1 inhibitor group and paclitaxel+SIRT1 agonist group ( n=12). Neuropathic pain model in the later 3 groups was prepared by intraperitoneal injection of paclitaxel at 8 mg/kg on the 1 st, 4 th and 7 th d of experiment, respectively; rats in the paclitaxel+SIRT1 inhibitor group and paclitaxel+SIRT1 agonist group were respectively injected with SIRT1 inhibitor EX527 or agonist SRT1720 30 min before the first injection of paclitaxel. In addition, neuropathic pain model was established in 12 rats (model group) by the same method and SIRT1 expression in the dorsal root ganglion tissues was detected by Western blotting 1 d before experiment and on the 3 rd, 7 th and 14 th d of experiment, respectively. Von-Frey filament was used to detect the 50% paw withdrawal mechanical threshold (PWMT), and thermal radiation thermal pain detector was used to evaluate the paw withdraw thermal latency (PWTL) 1 d before experiment and on the 3 rd, 7 th and 14 th d of experiment. On the 7 th d of experiment, 6 rats in each group were sacrificed with excessive anesthesia after PWMT and PWTL detection; L 4-L 6 dorsal root ganglion tissues were rapidly isolated and primary neurons were cultured; Western blotting was used to detect SIRT1 expression in the dorsal root ganglion tissues, JC-1 mitochondrial membrane potential detection kit was used to detect mitochondrial membrane potential (ratio of orange-red fluorescence to green fluorescence), hydrogen peroxide (H 2O 2) detection kit was used to detect H 2O 2 concentration, and mitochondrial superoxide detection kit and mitochondrial green fluorescence probe kit were used to detect mitochondrial superoxide expression. Results:In the model group, SIRT1 expression in the dorsal root ganglion tissues one d before experiment was significantly decreased compared with that on the 3 rd, 7 th and 14 th d of the experiment ( P<0.05). On 3 rd, 7 th and 14 th d of experiment, compared with the solvent control group, the paclitaxel group had significantly decreased 50% PWMT ([6.37±2.27] g, [5.47±2.42] g and [5.34±1.74] g), and PWTL ([9.38±1.27] s, [9.70±1.97] s and [9.12±1.21] s, P<0.05); compared with the paclitaxel group, the paclitaxel+SIRT1 agonist group had significantly increased 50% PWMT ([13.86±3.72] g, [11.87±3.10] g and [12.39±2.94] g) and PWTL ([14.25±2.63] s, [13.29±2.94] s and [14.43±3.91] s), and the paclitaxel+SIRT1 inhibitor group had significantly decreased 50% PWMT [(2.20±1.43] g, [2.43±1.44] g and [2.21±1.56] g) and PWTL ([4.47±1.66] s, [3.65±1.80] s and [3.14±1.59] s, P<0.05). On the 7 th d of experiment, the paclitaxel group had significantly decreased SIRT1 protein expression (53.95±7.37) and ratio of orange-red fluorescence to green fluorescence (48.74±14.57), and significantly increased H 2O 2 concentration ([4.86±0.69] μmol/L) and mitochondrial superoxide expression (180.17±12.08) in the dorsal root ganglion tissues compared with the solvent control group ( P<0.05); compared with the paclitaxel group, the paclitaxel+SIRT1 agonist group had significantly increased SIRT1 expression (97.51±10.09) and ratio of orange-red fluorescence to green fluorescence (83.52±8.60) and decreased H 2O 2 concentration ([2.30±0.39] μmol/L) and mitochondrial superoxide expression (90.17±18.84) in the dorsal root ganglion tissues ( P<0.05); compared with the paclitaxel group, the paclitaxel+SIRT1 inhibitor group had significantly decreased SIRT1 expression (30.80±6.31) and ratio of orange-red fluorescence to green fluorescence (24.60±6.19) and increased H 2O 2 concentration ([10.67±1.85] μmol/L) and mitochondrial superoxide expression (294.52±26.94) in the dorsal root ganglion tissues ( P<0.05). Conclusion:SIRT1 activation can alleviate paclitaxel-induced neuropathic pain by inhibiting mitochondrial damage in dorsal root ganglion neurons.

Objective:Head and neck squamous cell carcinoma（HNSCC） is one of the common malignant tumours, and most of them are in locally advanced stages at the time of diagnosis due to the lack of early symptoms, and the prognosis of such patients is still poor. M6A modification is the most common form of RNA modification in eukaryotic organisms, with a wide range of biological functions, and the family of IGF2BPs modulates growth, metastasis, chemotherapy resistance, and other processes of cancer by binding to and stabilizing a wide range of target RNAs through recognition of the m6A locus. The aim of this paper is to review the role and related mechanisms of IGF2BPs in head and neck squamous carcinoma, and to provide new ideas for early diagnosis and precision treatment of HNSCC.
Humans ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Head and Neck Neoplasms/pathology* ; Carcinoma, Squamous Cell/pathology* ; RNA-Binding Proteins/genetics* ; Prognosis

Objective:To evaluate the effect of the improved team-based learning (TBL) teaching method in the undergraduate probation course of ophthalmology based on the goal of cultivating excellent doctors.Methods:The undergraduates of clinical medicine were randomly divided into experimental group and control group. The control group ( n=50) was given conventional ophthalmology probation teaching, while the experimental group ( n=50) was given ophthalmology probation teaching of improved TBL teaching method. The theoretical examination performance and skill assessment results of students in the two groups were compared, and the subjective evaluation of the students on the teaching was also compared. SPSS 23.0 was used to conduct t-test and Wilcoxon's rank sum test. Results:The theoretical examination performance of experimental group (29.68±4.52) was better than that of control group (27.84±4.33), with significant differences ( P<0.05); the skill assessment results of experimental group (32.88±5.05) were also better than those of the control group (30.88±6.99), with significant differences ( P<0.05); the subjective evaluation of teaching effect in each item of experimental group was better than that of control group ( P<0.05). Conclusion:The improved TBL teaching method can not only improve students' theoretical knowledge and experimental skills, but also improve students' self-study and teamwork ability, which will provide a feasible educational reform plan for achieving the goal of cultivating excellent doctors.

The common clinical subtypes of juvenile idiopathic arthritis (JIA) include systemic onset juvenile idiopathic arthritis (SOJIA), oligoarthritis/polyarthritis juvenile idiopathic arthritis and juvenile spondyloarthritis. Juvenile idiopathic arthritis has no specific diagnostic index, and needs to be differentiated from infectious diseases and malignant diseases. The onset of SOJIA is rapid, the disease progresses rapidly, and it is easy to be complicated with macrophage activation syndrome (MAS) which is life-threatening. The experience of pediatric rheumatologists in dealing with JIA is still insufficient, and the standardized diagnosis and treatment level of this disease needs to be further improved. Based on the experience and guidelines of diagnosis and treatment in China and abroad, we formulated this diagnosis and treatment standard, aiming at standardizing the diagnosis and treatment of the subtypes of JIA and MAS, so as to reduce the incidence of disability and serious complications and improve the prognosis.

The traditional view is that breast reconstruction is not an option for day surgery center. As a result, few hospitals in the world conduct this operation in day surgery center. Endoscopic breast reconstruction with liposuction and robot-assisted breast reconstruction are minimally invasive surgeries for breast cancer patients, but they cannot be carried out in the day surgery center due to long operation time. The novel endoscopic-assisted immediate implant-based breast reconstruction after nipple sparing mastectomy through a single axillary incision for breast cancer patients has been successfully conducted in the day surgery center in our hospital due to short operation time and small trauma. Standardized management of the complete process from the patient selection to follow-up after discharge brings rapid recovery and few complications. At the same time, the development of endoscopic surgery makes the breast almost scarless and improves aesthetic results. Therefore, the mode of endoscopic-assisted reconstruction in the day surgery center of our hospital is expected to be popularized in the whole country.

Objective    To explore the surgical technique and preliminary results of endoscopic nipple-sparing mastectomy (E-NSM) and immediate pre-pectoral implant-based breast reconstruction (BR) with titanium-coated polypropylene mesh (TiLoop Bra) via single axillary incision for breast cancer patients. Methods    The clinical data of 9 consecutive female patients who underwent E-NSM and immediate pre-pectoral implant-based BR with TiLoop Bra from  March to May 2021 were retrospectively analyzed. The mean age of patients was 40.6 (22-60) years. The operation time, early complications were collected, and the patients' social and mental health, breast satisfaction and chest function before and after the operation were assessed with the BREAST-Q questionnaire. Results    All the patients had unicentric tumor with a mean diameter of 2.4 (0.6-4.7) cm. The mean distance from the tumor to the nipple was 2.5 (2-4) cm. There were 2 patients with tumor stage 0 and 7 patients with stageⅠ. The mean operation time was 161.1 (125-201) min, the mean blood loss was 41.1 mL and the hospital stay time was 1.5 d. There were 5 patients in the day-care unit. All the patients were successfully followed up with a median follow-up time of 1 (1-2) month. One (11.1%) patient with depigmentation of the nipple-areola complex caused by mild ischemia. None of the patients had incision complications, subcutaneous emphysema, hematoma, infection, nipple-areola or skin flaps necrosis, implant loss. During the follow-up period, no local/regional recurrence or distant metastasis was found. Chest well-being was decreased in the first month after the surgery compared with preoperative status, and the difference was statistically significant (P=0.001). There was no statistical difference in the breast satisfaction or psychosocial function scores between pre- and post-operation (P>0.05). Conclusion    E-NSM and immediate pre-pectoral implant-based BR with TiLoop Bra via single axillary incision has minimal trauma, rapid postoperative recovery, short operation time, few early complications and good early cosmetic effect, and the short-term result is satisfactory.