Child ; Humans ; Mpox (monkeypox)/prevention & control* ; Disease Outbreaks

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.

The author analyzed the characteristics of phase Ⅰ clinical trials of macromolecular drugs,the characteristics of evaluation indicators of phase Ⅰ clinical trials of macromolecular drugs,such as safety evaluation,pharmacokinetic and pharmacodynamic evaluation,and efficacy evaluation.And the control points of subjects management,management of experimental macromolecule drugs,and identified and potential risk factors of macromolecule drugs in the implementation of risk management for phase Ⅰ clinical trials of macromolecule drugs were discussed in depth based on previous clinical trial research experience.Through discussion and analysis,the author suggests that each research center can formulate risk control strategies according to the actual situation,improve the efficiency of risk control,and facilitate the smooth implementation of clinical trials and improve the quality of clinical trials.

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.

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family. To our knowledge, this is the first report of a carbapenem-resistant L. adecarboxylata strain isolated from a healthy newborn. The L. adecarboxylata strain isolated in this study carried four plasmids that may serve as reservoirs for antibiotic resistance genes. Plasmids 2 and 4 did not harbor any antimicrobial resistance genes. Plasmid 3 is a novel plasmid containing three resistance genes. The bla _IMP gene harbored in the strain was most similar to bla _IMP-79 at the nucleotide level, with a similarity of 99.4% (737/741). This case highlights the importance of considering L. adecarboxylata as a potential cause of infections in children.
Infant, Newborn ; Child ; Humans ; Female ; Enterobacteriaceae Infections/microbiology* ; Enterobacteriaceae/genetics* ; Anti-Bacterial Agents/therapeutic use* ; Plasmids

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

Objective: To study the relationship between the onco-immunological and morphologic characteristics of lymphoepithelioma-like carcinoma (LELC) and peripheral blood lymphocyte subtypes and its clinical significance. Methods: The pathologic and clinical data of 117 LELC patients who were admitted to the Tumor Hospital of the University of Chinese Academy of Sciences from 2006 to 2018 were collected. The histological classification was based on previously reported morphological classification method. The onco-immunological and morphologic characteristics of the tumors such as lymphoid follicle formation and interstitial fibrous hyperplasia, patient's peripheral blood lymphocyte subtypes and prognosis data were collected. The relationship between various factors and their impact on prognosis were analyzed. Results: There were 117 patients, including 61 females and 56 males. The male to female ratio was 0.9∶1.0. The age of onset was 24-89 years (median 52 years). Primary sites included head and neck (68 cases), lungs (26 cases), stomach (15 cases), and others (eight cases). Morphologically, 54 cases were type Ⅰ, 62 cases were type Ⅱ, and one case could not be classified. The onco-immunological and morphologic features of the LELC tumors showed a continuous spectrum. Interstitial TILs were noted from focally to diffuse, and the interstitial fibrous tissues were from hardly visible to obvious sclerotic. Formation of lymphoid follicles was seen in 42 patients; obvious fibrosis was seen in 31 cases. Data of peripheral blood lymphocyte subtyping by flow cytometry were available in 73 cases. These data included CD3⁺total T cells, CD3⁺CD4⁺helper T cells, CD3⁺CD8⁺cytotoxic T cells, CD3^-CD56⁺natural killer (NK) cells, CD3^-CD19⁺B cells, CD4⁺CD45RA^-T helper induction subgroup, CD4⁺CD45RA⁺ T suppression induction subgroup, CD4⁺CD45RO⁺memory T cell subgroup, CD45RA⁺CD45RO⁺activated T cell subgroup, CD8⁺CD38⁺activated cytotoxic T cell, and CD25⁺lymphocytes and CD44⁺lymphocyte. The proportion of lymphocytes of each subtype was normal in most patients, but the proportion of CD44⁺lymphocytes in 61 cases (83.6%) was increased; the proportion of T cell suppression induced subgroups was decreased in 53 cases (72.6%). Correlation analysis found a significant correlation between clinical stage and NK cells (P=0.023); tumor histologic type and cytotoxic T cells were significantly positively correlated (P=0.012); while tumor cell morphologic differentiation was significantly related to total T cells (P=0.003) and NK cells (P=0.026); Formation of interstitial lymphoid follicles was positively correlated with memory T cell subsets (P=0.025); Tumor interstitial fibrosis was significantly positively correlated with T suppression-induced subpopulations (P=0.004), and was significantly negatively correlated with total T cells (P=0.023) and with the expression of CD44 adhesion molecules (P=0.003). Survival analysis found that lymphoid follicle formation was a favorable prognostic factor for LELC (P=0.001). Conclusions: The onco-immunological and morphologic features in LELC show a continuous spectrum; the tumor clinicopathological characteristics and onco-immunological morphology are closely related to peripheral blood T lymphocyte subtypes, and the formation of interstitial lymphoid follicles is a favorable prognostic factor for LELC.
Adult ; Aged ; Aged, 80 and over ; Carcinoma/metabolism* ; Female ; Fibrosis ; Flow Cytometry ; Humans ; Killer Cells, Natural/metabolism* ; Leukocyte Common Antigens/metabolism* ; Male ; Middle Aged ; Young Adult

ObjectiveTo explore the effect of Chaishao Liujuntang on Hedgehog signaling pathway in rats with chronic atrophic gastritis （CAG） of liver depression and spleen deficiency. MethodWistar rats were randomized into normal group and modeling group. CAG with the liver depression and spleen deficiency syndrome was induced in rats in the modeling group with a compound method. After modeling， they were classified into the model group， vitacoenzyme group， Chaishao Liujuntang group， GDC-0449 （blocker） group， and Chaishao Liujuntang + GDC-0449 group. Normal group and model group were given （ig） normal saline. Vitacoenzyme and Chaishao Liujuntang group received （ig） corresponding drugs at 240 mg·kg^-1·d^-1 and 5.1 g·kg^-1·d^-1， respectively， and GDC-0449 group was treated （ip） with GDC-0449 at 50 mg·kg^-1·d^-1. For the Chaishao Liujuntang + GDC-0449 group， rats received GDC-0449 （ip） at 50 mg·kg^-1·d^-1 and Chaishao Liujuntang （ig） at 5.1 g·kg^-1·d^-1. The administration lasted 4 weeks. The pathological morphology of rat gastric mucosa was observed based on hematoxylin-eosin （HE） staining. mRNA and protein expression of sonic hedgehog （Shh）， 12th transmembrane receptor Patched1 （Ptch1）， and glioma-associated oncogene homolog 1 （Gli1） in gastric mucosa tissues was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot. Content of serum interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with normal group， the model group demonstrated decrease in gland cells， glandular atrophy， large lumen volume， plasma cell infiltration， intestinal metaplasia， decrease in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa （P<0.01）， and rise of serum IL-1β and TNF-α content （P<0.01）. Compared with model group， vitacoenzyme group and Chaishao Liujuntang group showed ordered cells， alleviation of gland atrophy， and no obvious inflammatory infiltration， and GDC-0499 group and Chaishao Liujuntang + GDC-0449 showed no significant improvement. Significant rise in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa tissues of vitacoenzyme group and Chaishao Liujuntang group （P<0.01）， no significant difference in serum IL-1β content and significant decrease in TNF-α content in vitacoenzyme group （P<0.01）， significant reduction in content of serum IL-1β and TNF-α in Chaishao Liujuntang group （P<0.05， P<0.01） were observed compared with those in the model group. The mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa and the content of serum IL-1β and TNF-α were insignificantly different between the GDC-0449 group and Chaishao Liujuntang + GDC-0449 group. ConclusionChaishao Liujuntang can effectively improve the pathological state of gastric mucosa in CAG rats with liver depression and spleen deficiency， which may be related to the activation of Hedgehog signaling pathway and the decrease of IL-1β and TNF-α content.

ObjectiveTo explore the guidance value of “treatment of disease in accordance with three conditions” theory in the prevention and treatment of corona virus disease 2019（COVID-19） based on the differences of syndromes and traditional Chinese medicine（TCM） treatments in COVID-19 patients from Xingtai Hospital of Chinese Medicine of Hebei province and Ruili Hospital of Chinese Medicine and Dai Medicine of Yunnan province and discuss its significance in the prevention and treatment of the unexpected acute infectious diseases. MethodDemographics data and clinical characteristics of COVID-19 patients from the two hospitals were collected retrospectively and analyzed by SPSS 18.0. The information on formulas was obtained from the hospital information system （HIS） of the two hospitals and analyzed by the big data intelligent processing and knowledge service system of Guangdong Hospital of Chinese Medicine for frequency statistics and association rules analysis. Heat map-hierarchical clustering analysis was used to explore the correlation between clinical characteristics and formulas. ResultA total of 175 patients with COVID-19 were included in this study. The 70 patients in Xingtai，dominated by young and middle-aged males，had clinical symptoms of fever， abnormal sweating，and fatigue. The main pathogenesis is stagnant cold-dampness in the exterior and impaired yin by depressed heat， with manifest cold， dampness， and deficiency syndromes. The therapeutic methods highlight relieving exterior syndrome and resolving dampness， accompanied by draining depressed heat. The core Chinese medicines used are Poria，Armeniacae Semen Amarum，Gypsum Fibrosum，Citri Reticulatae Pericarpium，and Pogostemonis Herba. By contrast，the 105 patients in Ruili， dominated by young females， had atypical clinical symptoms， and most of them were asymptomatic patients or mild cases. The main pathogenesis is dampness obstructing the lung and the stomach， with obvious dampness and heat syndromes. The therapeutic methods are mainly invigorating the spleen， resolving dampness， and dispersing Qi with light drugs. The core Chinese medicines used are Poria，Atractylodis Macrocephalae Rhizoma，Glycyrrhizae Radix et Rhizoma，Coicis Semen，Platycodonis Radix，Lonicerae Japonicae Flos， and Pogostemonis Herba. ConclusionThe differences in clinical characteristics， TCM syndromes， and medication of COVID-19 patients from the two places may result from different regions，population characteristics， and the time point of the COVID-19 outbreak. The “treatment of disease in accordance with three conditions” theory can help to understand the internal correlation and guide the treatments.