Objective To summarize and analyze the clinical phenotypes,hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas(PCC/PGL)and related syndromes.Methods Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled,and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection,and Sanger sequencing was applied to verify the mutation of the probands and family members.Results There were 15 patients diagnosed with hereditary PCC/PGL,including 7 cases of von Hippel-Lindau(VHL)syndrome,3 cases of multiple endocrine neoplasia type 2(MEN2),and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A(c.500G＞A),VHL2B(c.239G＞T and c.444_457del),and VHL2C(c.293A＞G)according to their clinical manifestations.All probands received surgical treatment,and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G＞C,c.1832G＞A,and c.1901G＞A missense mutations,respectively,and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy,including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families,4 patients carried SDHB mutations(SDHB:c.343C＞T,c.541-2A＞G,c.575G＞A,c.268C＞T)and 1 patient carried an SDHD mutation(SDHD:c.337_340del).Sporadic retroperitoneal PGL were most common.Conclusion More than 1/3 of PCC/PGL patients carry germline gene mutations,showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up,and genetic counseling.

Ulcerative colitis(UC)is a chronic im-mune-mediated disease characterized by diffuse mucosal inflammation and clinical symptoms of ab-dominal pain,diarrhea,mucopurulent bloody stool and tenesmus.Due to its complex etiology,difficult treatment and poor prognosis,UC has been listed as one of the modern refractory diseases by the World Health Organization.MicroRNAs(microR-NAs)regulate various biological processes such as cell growth,differentiation,and development by regulating gene expression.Studies have shown that miRNA is involved in the pathogenesis of UC through various pathways such as intestinal muco-sal barrier homeostasis disorder,intestinal flora im-balance and excessive differentiation of immune cells,and is expected to become a new target for clinical treatment of UC.In order to better under-stand the role of miRNA in the pathogenesis of UC and provide new research directions for the treat-ment of UC,this article reviews the correlation be-tween miRNA and the pathogenesis of UC,the po-tential of miRNA as a biomarker of UC,and the treatment strategies of miRNA in UC in recent years.

Myelodysplastic syndrome(MDS)is a malignant clonal disease with high heterogeneity in cytogenetics and molecular genetics,and the risk of progression to acute myeloid leukemia(AML)is extremely high.Transforming growth factor-β(TGF-β)is closely related to the pathogenesis of MDS.It is a key executor of immune homeostasis and immune tolerance,and can inhibit the expansion and function of many components of immune system.TGF-β signaling pathway can regulate hematopoietic cells and immune cells in microenvironment,inhibit their normal biological functions,and thus accelerate the progression of MDS.This study reviews regulatory effects of TGF-β signaling pathway on MDS blood cells,T lymphocytes,natural killer cells and macrophages in recent years,and provides a new perspective for the pathogenesis and treatment of MDS.

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.
Mice ; Animals ; Microcephaly/genetics* ; Autistic Disorder/metabolism* ; Autism Spectrum Disorder/metabolism* ; Nerve Tissue Proteins/metabolism* ; Brain/metabolism* ; Mice, Knockout ; Cell Cycle Proteins/metabolism*

As the National Health Commission changes the management of novel corona virus infection, the situation and preventive policies for controlling the epidemic have also entered a new stage in China. Perioperative care strategies for orthopedic trauma such as designated isolation and nucleic acid test screening have also been adjusted in the new stage. Based on the perioperative work experiences in the new stage of epidemic from the frontline anti-epidemic staff of orthopedics in domestic hospitals and combined with the literature and relevant evidence-based medical data in perioperative care of orthopedic trauma patients under the current anti-epidemic policies at home and abroad, Chinese Orthopedic Association and Chinese Society of Traumatology organized relevant experts to formulate the Guideline for clinical perioperative care of orthopedic trauma patients in the new stage of novel corona virus infection ( version 2023). The guideline summarized 16 recommendations from the aspects of preoperative diagnosis and treatment, infection prevention, emergency operation and postoperative management to systematically standardize the perioperative clinical pathways, diagnosis and treatment processes of orthopedic trauma in the new stage of novel corona virus infection, so as to provide a guidance and reference for hospitals at all levels to carry out relevant work in current epidemic control policies.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

High-throughput sequencing has the characteristics of complex experimental procedures, multiple quality control nodes, and a high proportion of bioinformatics technology. It is difficult to uniformly management and reuse the related detection samples and data. In May 2023, a tertiary hospital launched the construction of a localized high-throughput sequencing management system. Based on the design principles of security, friendliness, compatibility, and scalability, the management system had established three core modules: standardized data collection integration, clinical high-throughput sequencing full process management, and scientific research services, as well as a large clinical high-throughput sequencing database of hospital. By connecting with big data storage devices, local and third-party high-throughput sequencing detection platforms, sample libraries, and user terminals, this system broke down the data barriers of high-throughput sequencing related systems and devices, and met the different application scenarios of physician users, technician users, management users, and scientific research users in the hospital. As of October 2023, the system had been integrated with two high-throughput sequencing manufacturer devices in a public network environment and hospital information systems in an internal network environment, improving data retrieval efficiency and achieving closed-loop management of high-throughput sequencing detection projects preliminary, which can provided references for promoting the standardized management of high-throughput sequencing projects in hospitals in China.

Objective:To explore the effect of different HER2 expression levels and gene amplification on the efficacy of immunotherapy in metastatic urothelial carcinoma (UC).Methods:The clinical data of 77 patients with metastatic UC who received immunotherapy from June 2017 to April 2021 after failure to the previous chemotherapy were analyzed retrospectively, including 49 males and 28 females with the median age of 62 years. The primary tumors located in bladder in 28 cases (36.4%), renal pelvis in 25 cases (32.5%) and ureter in 24 cases (31.2%). The common metastatic sites included: lymph nodes (n = 45, 58.4%), lung (n = 40, 51.9%), bone (n = 20, 26.0%) and liver (n = 16, 20.8%). 27 patients with bladder UC received surgery on the primary tumors including radical cystectomy (n = 18), partial cystectomy (n = 4) and transurethral resection (n = 5). 43 patients with renal pelvis or ureteral UC received surgery on the primary tumors including radical nephroureterectomy (n = 38), local resection (n = 3) and palliative resection (n = 2). Postoperative intravesical chemotherapy was performed in 15 cases, adjuvant radiotherapy was performed in 6 cases. 3 patients who emerged postoperative bladder recurrence received local radiotherapy. 7 patients received radiotherapy and 1 case received microwave ablation to their metastatic sites. All patients had received first-line chemotherapy and 30 patients (40.0%) had received at least second-line treatment including 70 cases (90.9%) with platinum containing chemotherapy. All 77 patients received anti-PD-1 treatment. 38 patients received sequential regimen after failed to the anti-PD-1 therapy, including antibody-drug conjugate (n = 17), chemotherapy (n = 18) and chemotherapy combined with anti-angiogenesis drugs (n = 12). Immunohistochemical (IHC) staining was used to detect the expression level of HER2 protein in the tumor tissues (74 cases from primary tumors and 3 cases from metastatic tumors) obtained from the initial diagnosis. For patients with HER2 IHC (+ + ), the copy number (CN) of HER2 gene was detected by next-generation sequencing (NGS). HER2 copy number amplification [CN (+ )] was defined as CN ≥ 4, and HER2 copy number non-amplification [CN(-)] was defined as CN < 4. HER2 IHC (0) was defined as HER2 negative, IHC (+ ) or IHC (+ + ) / CN (-)was defined as HER2 low expression, while IHC (+ + ) / CN(+ ) and IHC (+ + + ) were defined as HER2 high expression. Chi-square test or Fisher exact test were used to evaluate the correlation between HER2 expression and objective response rate (ORR) after anti-PD-1 treatment. Kaplan-Meier method and log-rank test were used to compare the differences of median progression free survival (PFS) and overall survival (OS) under different HER2 expression status.Results:All the 77 patients received a median of 11 (range: 2 - 45) doses of anti-PD-1 treatment with a median duration of treatment of 6.4 (range: 1.5 - 47.8) months and the ORR was 33.8% (26/77). The median follow-up time was 30.9 months. The overall median PFS time was 5.8 (95% CI: 3.0 - 8.6) months and the median OS time was 23.6 (95% CI: 8.5 - 38.7) months. HER2 IHC tests were performed in 77 patients. HER2 IHC levels of (0), (+ ), (+ + ) and (+ + + ) were found in 33 (42.9%), 19 (24.7%), 20 (26.0%) and 5 (6.5%) patients, respectively. HER2 copy number was detected in 20 patients with IHC (+ + ), while 1 CN(+ ) and 19 CN(-) were found. The ORR of HER2 negative, low expression and high expression patients were 42.4% (14/33) vs. 31.6% (12/38) vs. 0 (0/6) ( P = 0.08), respectively. The median PFS of the three groups were 11.0 months, 3.7 months and 1.8 months, respectively, with significant differences in overall and pairwise comparison( P=0.001). The median OS of patients with HER2 negative and low expression after anti-PD-1 treatment were 23.6 months and 22.7 months, respectively, while the median OS of patients with HER2 high expression had not been reached, with no significant difference in the overall comparison ( P=0.623). Conclusions:For patients with metastatic UC received anti-PD-1 treatment, the PFS of patients with high HER2 expression was significantly worse than that of patients with low or negative HER2 expression. HER2 expression may have potential value in predicting the efficacy of immunotherapy for metastatic UC who failed the previous chemotherapy, which needs further research.

In recent years, with the wide application of magnetic resonance imaging (MRI) equipment in clinical practice, the quality of the equipment causes adverse events, which put pressure on manufacturers, at the same time, it puts forward higher requirements for medical device supervisors. In order to help the medical device supervisors to clarify the key points of verification, this paper analyzes the main risk points in the production process of the product according to the medical device good manufacturing practice(GMP), and puts forward the suggestions for field verification, which has practical significance for the submission of verification efficiency.
Commerce ; Magnetic Resonance Imaging

Objective:To investigate the effects of Sacubitril/Valsartan on the recurrence of atrial fibrillation(AF), cardiac structure and function after catheter ablation(CA)of persistent AF.Methods:A total of 180 patients with persistent AF were randomly divided into the treatment group(n=90)and the control group(n=90)before undergoing CA.The control group was given routine perioperative medication according to the guidelines for AF management, and the treatment group was additionally given Sacubitril/Valsartan.Blood pressure, N-terminal pro-B-type natriuretic peptide(NT-proBNP), P-wave dispersion, left atrial dimension, left atrial volume index, mitral regurgitation area, left ventricular end-systolic volume index, end-diastolic volume index and left ventricular ejection fraction(LVEF)were measured at 3, 6 and 12 months after the procedure.Results:Blood pressure was lower in the treatment group than in the control group( P<0.05), but no hypotension or related symptoms occurred.The sinus rhythm maintenance rate was higher in the treatment group than in the control group at 3, 6 and 12 months during the follow-up(80.0%, 72.2%, 78.9% vs.70.0%, 75.6%, 68.9%, χ2=4.866, 6.667 and 4.091, P=0.027, 0.010 and 0.043, respectively). At 6 and 12 months during the follow-up, NT-proBNP, P-wave dispersion, left atrial diameter, left atrial volume index, mitral regurgitation area, left ventricular end-systolic volume index and end-diastolic volume index were lower(all P<0.05)and LVEF was higher( P<0.05)in the treatment group than in the control group. Conclusions:In patients with persistent AF after CA, Sacubitril/Valsartan has favorable effects in maintaining sinus rhythm, reversing cardiac remodeling and improving cardiac function.