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.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ² Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic ; Antiviral Agents/therapeutic use* ; DNA, Viral/therapeutic use* ; Retrospective Studies ; Mutation ; Drug Resistance, Viral/genetics* ; Lamivudine/therapeutic use*

Ferroptosis is a new type of cell death caused by abnormal accumulation of iron-dependent reactive oxygen species （ROS） and imbalance of redox with the participation of iron ions. In recent years， studies have found that ferroptosis is associated with various diseases and can especially regulate the development of tumors. Chinese medicine has unique advantages in tumor prevention and treatment. How to use ferroptosis theory to guide the prevention and treatment of cancer and other tumor diseases by Chinese medicine is a new research hotspot. This paper summarizes the proposal， action mechanism， and signaling pathway of ferroptosis， its application in tumor therapy， and the research on the activity of Chinese medicine based on ferroptosis. Results found that the occurrence of ferroptosis is related to iron metabolism， lipid ROS metabolism， and other signaling pathways and gene expressions. Ferroptosis can regulate tumor initiation and development， treatment， and tumor immunity， which provides strategies for tumor treatment and anti-tumor drug development. By analyzing the biological activity of Chinese medicine against ferroptosis， we found that Chinese medicines （Scutellariae Radix， Puerariae Lobatae Radix， Astragali Radix， Ginkgo， Epimedii Folium， Artemisiae Annuae Herba， and Salviae Miltiorrhizae Radix et Rhizoma）， Chinese herbal compounds （ Naotaifang， Si Junzitang， and Shenmai injection）， and Chinese medicine effective components （baicalein， dihydroartemisinin， puerarin， piperlongumine， luteolin， and quercetin） can exert antitumor and other biological activities by regulating ferroptosis. Therefore， Chinese medicine has great potential in preventing and controlling tumors and other diseases by regulating ferroptosis. This paper provides theoretical basis and research ideas for the in-depth study of ferroptosis theory and guides the prevention and treatment of tumor diseases by Chinese medicine.

Diabetes is a worldwide public health problem that seriously threats human health. Long-term metabolic disorders， as the main cause of multi-system complications and death in the later stage of diabetes， can cause multi-system damage， leading to chronic progressive lesions in the eyes， kidneys， nerves， heart， blood vessels and other tissues and organs， as well as functional decline and failure. The low risk of side effects and new treatment strategies remain an area to be explored in clinical treatment of diabetes. Salviae Miltiorrhizae Radix et Rhizoma （SM） is one of the commonly used herbs in traditional Chinese medicine （TCM）， with the main effect of activating blood circulation and removing blood stasis. In recent years， it has been found that SM shows good performance in lowering blood sugar and treating diabetes complications. Data mining information has also shown that the drugs of activating blood circulation and removing blood stasis are now common drugs in clinical treatment of diabetes， and SM has the highest use frequency， with significant curative effect. In addition， TCM is a kind of treatment with composite components and multiple targets， and so people are increasingly interested in its effective components and carry out extensive researches. This article summarized the experimental verification of SM extract and its components （tanshinone A， tanshinone B， tanshinone Ⅱ_A， tanshinone I， protocatechuic aldehyde， polysaccharide， and total polyphenol acid） in various diabetes models in improving glucolipid metabolism， improving heart function in patients with diabetes， alleviating the motor and sensory deficits caused by diabetes， preventing the occurence of the diabetic retinopathy， recovery of liver and kidney structure and function damage in diabetic patients， and helping to resist high sugar-induced atrophic cavitation potential. It may inhibit hyperglycemia-induced vascular injury with polyol pathway activation， reduce the formation of advanced glycation end products， inhibit protein kinase C pathway activation and hexosamine pathway activation， and alleviate oxidative stress caused by excessive production of peroxides in mitochondrial electron transport chain during hyperglycemia to play a role of treatment， and provide reference for clinical application.

OBJECTIVE: To assess the safety and efficacy of Neuroform EZ stent used in treatment of symptomatic complex severe intracranial atherosclerotic stenosis (ICAS). METHODS: Clinical data of 18 patients with symptomatic complex severe ICAS undergoing Neuroform EZ stent angioplasty from January 2016 to December 2017 were retrospectively analyzed. All the lesions of the patients in this group were considered as complex ICAS, i.e. with severe tortuous access, long (>10 mm) or occlusive or bifurcation lesions, with concurrent aneurysms near the stenotic lesion. The primary outcome was defined as any stroke (including ischemic or hemorrhagic) or deaths from any cause after stenting procedure within 30 days. The secondary outcome was defined as successful revascularization and occurrence of >50% in-stent restenosis during the follow-up period. RESULTS: All the 18 patients achieved technical success (100%) and mean stenosis rate was reduced from 85%±7% to 18%±6%. Of the 18 patients included, the 30-day stroke or death was 5.6% (1/18), which presented as basal ganglia region infarction in a patient with tandem lesions on the left vertebral artery. There was no hemorrhagic and death complications that occurred in the patients of this group. One concurrent aneurysm was embolized with micro coil (stent assisted) by stages after 1 month. In this group 12 patients were followed up with digital subtraction angiography (DSA) after hospital discharge. The follow-up period ranged from 8 months to 26 months [mean: (16±8) months]．During the follow-up period 2 patients in the 12 patients (2/12, 16.7%) developed in-stent restenosis (ISR) confirmed by DSA, and one of them was symptomatic restenosis and restored unobstructed blood flow after balloon angioplasty. CONCLUSION Neuroform EZ stent for the treatment of highly screened symptomatic complex severe ICAS is safe and effective. It has its advantages over traditional stent.
Cerebral Angiography ; Constriction, Pathologic ; Follow-Up Studies ; Humans ; Retrospective Studies ; Stents ; Treatment Outcome

Platelets are one of essential components of mammalian blood and play an important role in physiological and pathological reactions such as hemostasis, inflammatory response, thrombosis and rejection of organ transplantation. Platelet activation signal is the main physiological transmission mechanism that activates and induces platelets to play a physiological role, which has been the research focus in the field of physiological research in recent years. In this paper, we reviewed the new mechanisms of adhesion receptor-mediated calcium elevation, the new ideas of platelet activation mediated by pattern recognition receptors, and the new concept in platelet cGMP signaling and some other new researches.

OBJECTIVE To study the effects of Liuweidihuang Formula (LWDHF) on the ovariectomized ApoE-/-AS mice and the proliferation and migration of vascular smooth muscle cell (VSMCs) in vitro,and to elucidate the roles of estrogen receptor β (ERβ) and heat shock protein 27 (HSP27) phosphorylation in the context.METHODS The artery injury of ApoE /-mice was observed by HE staining and the phosphorylation of HSP27 in vessels was detected by immunohistochemistry.VSMC proliferation and cell cycle were examined by MTT assay and flow cytometry,respectively.VSMC migration was observed by wound-healing assay and F-actin staining.The levels of HSP27,pHSP27,cyclin D1,protein phosphatase 2 (PP2A) and ERβ were determined by Western blot analyses.Transfection with ERβ siRNA and ERα shRNA was carried out to investigate their roles in LWDHF effects,respectively.RESULTS LWDHF improved the arterial lesion,inhibited HSP27 phosphorylation,and increased the expression of PP2A and ERβ in ovariectomized ApoE / AS mice.In in vitro experiments,angiotensin Ⅱ (Ang Ⅱ) at 1 × 10-7 mol/L obviously induced VSMC proliferation and migration,increased the expression of cyclin D1 and cell number in the S phase,but these effects were significantly inhibited by LWDHF (12μg/mL).Further molecular examinations showed that LWDHF up-regulated PP2A expression through ERβ to inhibit HSP27 phosphorylation,contrib uting to inhibition of VSMC proliferation and migration.CONCLUSION LWDHF reduced menopause AS in vivo and inhibited proliferation and migration of VSMCs by regulating ERβ-inhibition of HSP27 phosphorylation in vitro.These discoveries provided novel molecular insights into LWDHF as potential therapy for AS.

Objective To study the incidence and risk factors ofdefecatory dysfunction in acute minorischemic strokepatientsandexplore the influence of the risk factors onprognosis.Methods Clinical data of 274 patients with acute minor ischemic strokewere reviewed and analyzed retrospectively.According to the presence of poststroke defecatorydysfunction,they were divided into defecatory dysfunction group and non-defecatory dysfunction group.The factors associated withdefecatory dysfunctionwere analyzed by univariate analysis and multivariatelogisticanalysis respectively,followed by investigating their effects on the prognosis.Results 74 patients of them with acute minor ischemic stroke had defecatory dysfunction.The univariate analysis indicated that4 factors including baseline NIHSS scorewere the risk factors.Multivariate logistic analysis showed that female,age,diabetes mellitus and baseline NIHSS score were independent risk factors for defecatory dysfunction.The scores of modified Rankin Scale (mRS) after 3 months in minor stroke patients with defecatory dysfunction wassignificantly higher(P ＜ 0.05).Baseline NIHSS score was a predictive factor for the prognosis of post-stroke defecatorydysfunctionpatients.Conclusions Defecatory dysfunction in acute minor stroke patients may increase the risk of poor prognosis.The female,elderlypatients as well those with diabetes mellitus and serious neurologicalfunction deficits are more likely to suffer post-stroke defecatory dysfunction.