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 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.

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.

Objective: To investigate the safety and feasibility of performing right colectomy via a transvaginal approach. Methods: This was a retrospeltive cohort study. Data of 30 patients who had undergone transvaginal laparoscopic right colectomy (transvaginal group) and 23 women who had undergone laparoscopic right colectomy (laparoscopic group) from January 2019 to March 2022 in the Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital were collected retrospectively. The inclusion criteria for the transvaginal group were as follows: (1) post-menopausal woman; (2) transverse diameter of the tumor < 6 cm; and (3) diagnosis of benign polyps that were unresectable by endoscopy, mucinous tumors of the appendix, or confirmed right colon cancer not requiring D3 lymphadenectomy. The inclusion criteria for the laparoscopic group were as follows: (1) pathologically confirmed adenocarcinoma or high-grade intraepithelial neoplasia; (2) lesion located from the cecum to the right third of the transverse colon; and (3) clinically stage T1-4NanyM0. The exclusion criteria for the laparoscopic group were as follows: (1) distant metastasis discovered during surgical exploration; (2) multiple organ resection required or R0 resection not possible; or (3) conversion to open surgery required. Safety was evaluated on the basis of intra- and post-operative complications. Feasibility was assessed by postoperative recovery and quality of operative specimen. The body mass index was lower in the transvaginal than the laparoscopic group (22.0±3.1 kg/m² vs. 24.1±2.6 kg/m², t=2.617, P=0.012). Results: Among the 30 transvaginal laparoscopic right colectomies, 26 were pure transvaginal surgeries, three required laparoscopic assistance because of difficulties with anastomosis (n=2) or abdominal adhesions (n=1), and one required conversion to laparoscopic surgery because of vascular injury. Compared with the laparoscopic group, the transvaginal group had a longer surgery time (175.0 [147.5, 216.3] minutes vs. 120.0 [100.0, 120.0] minutes, U=63.000, P<0.001) and more blood loss (30.0 [10.0, 50.0] ml vs. 23.0 [10.0, 20.0] ml, U=208.000, P=0.011). The incidence of intraoperative complications (16.7% [5/30) vs. 0, P=0.061] was comparable between the two groups. In the transvaginal group, the sites of intraoperative injuries were bladder (n=3), ileocecal artery (n=1), and right uterine artery (n=1). The incidence of postoperative complications (20.0% [6/30] vs. 17.4% [4/23], χ²<0.001,P>0.999) was also comparable between the two groups. Clavien-Dindo grade III postoperative complications occurred in two patients in the transvaginal group (one patient had a pelvic hematoma that required embolization; the other had a vesico-vaginal fistula that required surgery). Postoperative visual analogue scale scores were significantly lower (P<0.001) in the transvaginal group. Times to first flatus, ambulation, and first intake and duration of postoperative hospital stay were comparable between the two groups (P>0.05). The proportion of specimens of moderate quality was 83.3% (25/30) in the transvaginal group and 100% (23/23) in the laparoscopic group; this difference is not significant (P=0.061). Among patients who underwent D2 lymph node dissection, the number of lymph nodes examined was comparable between the transvaginal (n=23) and laparoscopic groups (n=7) (18 [15, 27] vs. 20 [16, 29], U=69.500, P=0.589). Conclusion: Transvaginal right colon surgery is associated with less postoperative pain than laparoscopic surgery, but is not yet the preferred alternative because of the incidence of surgical complications.
Humans ; Female ; Retrospective Studies ; Cohort Studies ; Feasibility Studies ; Treatment Outcome ; Postoperative Complications/epidemiology* ; Laparoscopy ; Colectomy

Sintilimab is an anti-programmed cell death receptor-1 antibody. The phase III clinical trial ORIENT-12 confirmed the safety of sintilimab combined with pemetrexed/platinum in the treatment of advanced squamous non-small cell lung cancer. Skin reactions are the most commonly reported adverse events of immune checkpoint inhibitors and are rarely severe.We describe a case of toxic epidermal necrolysis related to sintilimab in an elderly oncologic patient. 3 weeks after immunotherapy, the patient developed an extensive rash and diffuse itching, rapidly evolving into macules, blisters, bullae and erosions. Causal evaluation was performed based on the algorithm of drug causality for epidermal necrolysis and national Food and Drug Administration qualitative analysis. The patient responded to high-dose glucocorticosteroid and supportive therapy, alongside with local wound care. If immune checkpoint inhibitors need to be extrapolated clinically, strictly following evidence-based research, promptly detecting and treating adverse reactions is crucial.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

OBJECTIVE: To evaluate the feasibility of S₂ alar iliac screw insertion in Chinese children using computerized three-dimension reconstruction and simulated screw placement technique, and to optimize the measurement of screw parameters. METHODS: A total of 83 pelvic CT data of children who underwent pelvic CT scan December 2018 to December 2020 were retrospectively analyzed, excluding fractures, deformities, and tumors. There were 44 boys and 39 girls, with an average age of (10.66±3.52) years, and were divided into 4 groups based on age (group A:5 to 7 years old;group B:8 to 10 years old;group C:11-13 years old;group D:14 to 16 years old). The original CT data obtained were imported into Mimics software, and the bony structure of the pelvis was reconstructed, and the maximum and minimum cranial angles of the screws were simulated in the three-dimensional view with the placement of 6.5 mm diameter S2 alar iliac screws. Subsequently, the coronal angle, sagittal angle, transverse angle, total length of the screw, length of the screw in the sacrum, width of the iliac, and distance of the entry point from the skin were measured in 3-Matic software at the maximum and minimum head tilt angles, respectively. The differences among the screw parameters of S₂ alar iliac screws in children of different ages and the differences between gender and side were compared and analyzed. RESULTS: In all 83 children, 6.5 mm diameter S₂ iliac screws could be placed. There was no significant difference between the side of each screw placement parameter. The 5 to 7 years old children had a significantly smaller screw coronal angle than other age groups, but in the screw sagittal angle, the difference was more mixed. The 5 to 7 years old children could obtain a larger angle at the maximum head tilt angle of the screw, but at the minimum cranial angle, the larger angle was obtained in the age group of 11 to 13 years old. There were no significant differences among the age groups. The coronal angle and sagittal angle under maximum cephalic angle and minimum cranial angle of 5 to 7 years old male were (40.91±2.91)° and (51.85±3.75)° respectively, which were significantly greater than in female. The coronal angle under minimum cranial angle was significantly greater in girls aged 8-10 years old than in boys. For the remaining screw placement angle parameters, there were no significant differences between gender. The differences in the minimum iliac width, the screw length, and the length of the sacral screws showed an increasing trend with age in all age groups. The distance from the screw entry point to the skin in boys were significantly smaller than that of girls. The minimum width of the iliac in boys at 14 to 16 years of age were significantly wider than that in girls at the same stage. In contrast, in girls aged 5 to 7 years and 11 to 13 years, the screw length was significantly longer than that of boys at the same stage. CONCLUSION The pelvis of children aged 5 to 16 years can safely accommodate the placement of 6.5 mm diameter S₂ alar iliac screws, but the bony structures of the pelvis are developing and growing in children, precise assessment is needed to plan a reasonable screw trajectory and select the appropriate screw length.
Humans ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Ilium/surgery* ; Retrospective Studies ; Feasibility Studies ; Bone Screws ; Pelvis ; Sacrum/surgery* ; Spinal Fusion/methods*

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.
Humans ; Nonprescription Drugs ; Shock, Septic/drug therapy* ; Sepsis/drug therapy* ; Endotoxins ; Anticoagulants/therapeutic use*

Objective: To analyze the influencing factors of healthy life expectancy (HLE). Methods: Seven Chinese and English databases were used for the retrieval of related literatures published by May 7, 2022 to identify influencing factors of HLE, including diseases and injuries and their risk factors. Based on the ecological model of health determinants, this study classifies the risk factors of diseases and injuries into five levels: personal characteristics, individual behavior and lifestyle, social network, living and working conditions, and macroscopic socio-economic, cultural and environmental conditions. Contents of research area, HLE indicators, research population, influencing factors, data sources and results were extracted. The frequencies of reported documents of different HLE indicators and influencing factors of different dimensions were visualized by using evidence map, and the empirical studies of four authoritative English medical journals and Chinese core medical journals were further compared and described. Results: A total of 90 studies were selected, in which 26 were conducted in China (28.9%). Fifty-three studies are about diseases and injuries in the first dimension, and all of them have studied non-communicable diseases, accounting for the highest proportion (58.9%). There were 77 studies about the analysis on the determinants of health at five levels by an ecological model, all the studies reported multi-level results. Among them, 53 studies reported personal characteristics (58.9%), 47 studies reported individual behavior and lifestyle (52.2%), 10 studies reported social networks (11.1%), 35 studies reported living and working environment (38.9%), 8 studies reported social economy, culture status and environment condition (8.9%). The literatures about HLE published by 4 authoritative English medical journals and 21 Chinese core medical journals in recent three years were selected. Non-communicable diseases and personal characteristics were the top two most commonly studied factors of HLE, and 11 (52.3%) and 12 (57.1%) studies reported these two kinds of factors respectively. The most important factor contributing to the global disability-adjusted life years of non-communicable diseases was individual behavior and lifestyle, which was the most changeable factor. Conclusions: In recent three years, studies involving influencing factors of HLE were mainly non-communicable diseases and personal characteristics. In the future, individual behavior, lifestyle and working environment should be strengthened.
Humans ; Noncommunicable Diseases ; Healthy Life Expectancy ; Life Style ; Asian People ; Risk Factors

ObjectiveTo investigate the nephroprotective and anti-inflammatory effects of Fufang Shelong capsules （FFSL） in rats with membranous nephropathy （MN）， and the role of the p38 mitogen-activated protein kinase （MAPK） signaling pathway. MethodMale SD rats of SPF grade were divided into a normal group and an experimental group. The MN model was induced by tail vein injection of cationized bovine serum albumin in the experimental group. After screening， the eligible model rats were included and divided into a positive control group （tripterygium glycosides tablets） and low-， medium-， and high-dose FFSL groups （0.375， 0.75， 1.5g·kg^-1）. The rats were treated correspondingly for eight weeks， and urine protein was detected during drug intervention. Renal function and inflammation-related indicators were detected after drug intervention. The changes in 24-hour urine total protein （24 h UP）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， creatinine （Cr）， blood urea nitrogen （BUN）， total protein （TP）， albumin （Alb）， and total cholesterol （TC） were detected. Flow cytometry was used to detect CD4⁺/CD8⁺ changes. Kidney tissues were collected to observe pathological changes under a light microscope and an electron microscope. The protein expression of p38 MAPK and phosphorylated p38 MAPK （p-p38 MAPK） in kidney tissues was detected by Western blot. ResultCompared with the normal group， the model group showed increased 24 h UP （P<0.01）， elevated serum Cr， BUN， TC， IL-6， IL-8， and TNF-α （P<0.05，P<0.01）， decreased serum Alb and TP levels （P<0.05，P<0.01）， increased CD4⁺/CD8⁺ in the peripheral blood （P<0.01）， and up-regulated protein expression of p38 MAPK and p-p38 MAPK in kidney tissues （P<0.05）. Additionally， in the model group， immune complex deposition and foot process fusion， accompanied by infiltration of inflammatory cells， were observed on the epithelial side of the basement membrane in the pathological kidney tissues. Compared with the model group， the groups with drug intervention showed declining 24 h UP levels at six weeks （P<0.05，P<0.01）， decreased serum Cr， BUN， TC， IL-6， IL-8， and TNF-α （P<0.05，P<0.01）， increased serum Alb and TP levels （P<0.05，P<0.01）， reduced CD4⁺/CD8⁺ in the peripheral blood （P<0.01）， improved renal pathological damage， and down-regulated p38 MAPK and p-p38 MAPK in kidney tissues （P<0.05，P<0.01）. ConclusionFFSL can decrease the expression of inflammatory factors， reduce proteinuria， delay kidney damage， and protect kidney function by inhibiting the expression of the p38 MAPK signaling pathway.