ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (A_e) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10^-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.

Objective To evaluate the efficacy of vitamin C intravenous injection in the treatment of patients with sepsis.Methods PubMed,Embase,Scopus,Cochrane Library,and Clinical Trial databases were retrieved,with a retrieval period from database establishment to December 2022.English literatures on randomized controlled trial(RCT)of vitamin C intravenous injection for the treatment of sepsis or septic shock were collected.Meta-analysis was conducted using RevMan 5.3 software and Stata 15.0 software after literature screening,extraction,and evalua-tion of the bias risk included in the studies by two researchers independently.Results A total of 16 RCT studies involving 3 301 patients were included in the analysis.In terms of main outcomes,the 28-day mortality of patients in the vitamin C treatment group was slightly lower than that of the control group,but the difference was not statis-tically significant(RR=0.86,95％CI[0.72-1.03],P=0.10;I2=44％,P=0.10).In terms of secondary out-comes,vitamin C intravenous injection can reduce the duration of vasoactive drug usage time(MD=-23.44,95％CI[-30.53--16.35],P＜0.01;I2=0,P=0.97),but has no significant effect on the 90-day mortality,inten-sive care unit mortality,hospital mortality,duration of mechanical ventilation,difference in estimated sequential organ failure assessment score at 72 hour,length of stay in ICU,and total length of hospital stay of patients(P＞0.05).Conclusion Intravenous vitamin C injection can significantly reduce vasoactive drug usage time,but the available evidence is insufficient to support that intravenous vitamin C can improve the prognosis of patients with sepsis or septic shock.More high-quality,multicenter randomized controlled trial is needed to provide more substantial evidence about the efficacy of vitamin C in treating sepsis or septic shock.

OBJECTIVE: To explore the effects of veno-venous extra corporeal carbon dioxide removal (V-V ECCO₂R) on local mechanical power and gas distribution in the lungs of patients with mild to moderate acute respiratory distress syndrome (ARDS) receiving non-invasive ventilation. METHODS: Retrospective research methods were conducted. Sixty patients with mild to moderate ARDS complicated with renal insufficiency who were transferred to the respiratory intensive care unit (RICU) through the 96195 platform critical care transport green channel from January 2018 to January 2020 at the collaborative hospitals of Henan Provincial People's Hospital were enrolled. According to different treatment methods, they were divided into a conventional treatment group and an ECCO₂R group, with 30 patients in each group. Both groups received standard treatments including primary disease treatment, airway management, and non-invasive ventilation. The conventional treatment group received bedside continuous renal replacement therapy (CRRT), and the ECCO₂R group received V-V ECCO₂R treatment. General information of patient such as gender, age, cause of disease, and acute physiology and chronic health evaluation II (APACHE II) were recorded; arterial blood gas analysis was performed before treatment and at 12 hours and 24 hours during treatment, recording arterial partial pressure of oxygen (PaO₂), arterial partial pressure of carbon dioxide (PaCO₂), and oxygenation index (PaO₂/FiO₂). Respiratory mechanics parameters [tidal volume, respiratory rate, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP)] were recorded, and the rapid shallow breathing index (RSBI) was calculated; electrical impedance tomography (EIT) was used to measure regional of interest (ROI) values in different lung areas at 12 hours and 24 hours of treatment, and the pulmonary mechanical energy was calculated. RESULTS: The arterial blood gas analysis indicators, respiratory mechanics parameters, and pulmonary mechanical energy of patients in the conventional treatment group and ECCO₂R group improved significantly after 24 hours of treatment compared to 12 hours of treatment (all P < 0.05). The levels of PaCO₂, RSBI, total mechanical power, and non-dependent zone mechanical power in the ECCO₂R group were significantly lower than those in the conventional treatment group at both 12 hours and 24 hours during the treatment [PaCO₂ (mmHg, 1 mmHg ≈ 0.133 kPa): 44.03±2.96 vs. 49.96±2.50 at 12 hours, 41.65±3.21 vs. 48.53±2.33 at 24 hours; RSBI (times×min^-1×L^-1): 88.67±4.05 vs. 92.35±4.03 at 12 hours, 77.66±4.64 vs. 90.98±4.21 at 24 hours; total mechanical power (mJ): 10.40±1.15 vs. 12.93±1.68 at 12 hours, 11.13±1.18 vs. 14.05±1.69 at 24 hours; non-dependent zone mechanical power (mJ): 7.15±0.84 vs. 7.98±0.75 at 12 hours, 7.77±0.93 vs. 9.13±1.10 at 24 hours], and MEP and MIP in the ECCO₂R group were significantly higher than those in the conventional treatment group at both 12 hours and 24 hours during the treatment [MEP (cmH₂O, 1 cmH₂O ≈ 0.098 kPa): 89.88±5.04 vs. 86.09±5.57 at 12 hours, 96.57±2.59 vs. 88.66±2.98 at 24 hours; MIP (cmH₂O): 47.64±2.82 vs. 41.93±2.44 at 12 hours, 60.11±6.53 vs. 43.63±2.80 at 24 hours], the differences were statistically significant (all P < 0.05). CONCLUSIONS V-V ECCO₂R combined with non-invasive ventilation can effectively reduce the regional tidal volume, mechanical power, and respiratory rate in the non-gravitational dependent zones of patients with mild to moderate ARDS, and improve respiratory distress and oxygenation status.
Humans ; Respiratory Distress Syndrome/physiopathology* ; Retrospective Studies ; Carbon Dioxide ; Blood Gas Analysis ; Lung/physiopathology* ; Intensive Care Units ; Male ; Female ; Noninvasive Ventilation/methods* ; Continuous Renal Replacement Therapy/methods* ; APACHE ; Middle Aged

Humans ; SARS-CoV-2 ; COVID-19 ; Antibodies ; Antibodies, Viral/therapeutic use* ; Antibodies, Neutralizing/therapeutic use*

Objective:To investigate the diagnostic method and value of echocardiography in screening right patent ductus arteriosus(PDA) of infants.Methods:This was a prospective study.Thirty-one infants with right PDA diagnosed by ultrasound and confirmed by prenatal ultrasonography, electronic computed tomography angiography, angiocardiography and/or surgery in Hebei Children′s Hospital from April 2014 to May 2022 were collected as research subjects, and the association of right ductus arteriosus with aortic arch anomalies and complex cardiac malformations were summarized. The diagnostic method and value of ultrasonic screening were summed up.Results:Of the 31 cases, 30 cases were correctly diagnosed by ultrasound and 1 case was misdiagnosed, who was a left aortic arch descending to the right, a crossover variation of the right and left pulmonary arteries, and a rightward displacement of the ductus arteriosus. Among these cases diagnosed correctly, 27 cases (including 24 cases with right aortic arch and 3 cases with left aortic arch) presented that ductus arteriosus was open and its ostium of pulmonary artery end was located in the proximal right pulmonary artery in views of parasternal short-axis view of great vessels at cardiac base with the combination of two dimensions and color Doppler flow imaging. Other 3 cases of right aortic arch were all single ventricle with transposition of the great artery. Due to the parallel relationship of the two great arteries, the standard parasternal short-axis view of great vessels could not be obtained, and the right ductus arteriosus was found in the high parasternal views.In all of the 27 cases with right aortic arch and right ductus arteriosus, high parasternal views showed that one end of the ductus arteriosus was connected to the right aortic arch isthmus and the other end was connected to the right pulmonary artery. In all of the 3 cases with left aortic arch and right ductus arteriosus, the high parasternal views showed that one end of the ductus arteriosus was connected to the right subclavian artery and the other end was connected to the right pulmonary artery. Among the 27 cases with right aortic arch, 16 cases were accompanied with mirror image branches, 9 cases of which had complex cardiac malformations; 10 cases were associated with aberrant left subclavian artery, 1 case of which had complex cardiac malformations; 1 case was with isolated left subclavian artery, and without complex cardiac malformations. All 3 cases of left aortic arch were accompanied with isolated right subclavian artery and none of them were associated with complex cardiac malformations. Clinical outcomes of 30 cases with right PDA: 14 cases underwent ductus arteriosus ligation due to thick ductus or other heart malformations. In other 16 cases, 4 cases were closed spontaneously, 9 cases had persistent small ductus arteriosus, and 3 cases were lost to follow-up.Conclusions:Right ductus arteriosus is mostly related to the right aortic arch, and those with mirror image branches are prone to complex cardiac malformations; cases of left aortic arch with right ductus arteriosus are tend to accompany isolated right subclavian artery. Ultrasound has an important application in the screening and diagnosis of right PDA.

Objective To design a portable neck muscle training device to improve muscle strength around the neck and neck stability in pilots to reduce the incidence of neck disorders.Methods A portable neck muscle training device for pilots was designed based on a self-developed adaptive admittance force tracking control algorithm,which was composed of a damping generator,a transmission system,a fixation clamping mechanism,a head-mounted terminal,a control system,a power supply,a communication bus and a mobile App realized with Android Studio integrated development environment.Results The training device developed could be used for training of neck flexion,extension and rotation,which increased pilots'neck and shoulder activity angle,cervical curvature and strength intensity of each muscle group.Conclusion The training device gains advantages in portability,real-time feedback and low cost,and can be used for targeted training of neck muscles.[Chinese Medical Equipment Journal,2023,44(11):21-26]

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Humans ; Child ; Primary Myelofibrosis/genetics* ; Prognosis ; Mutation

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

Phenylalanine ammonia lyase (PAL) can catalyze L-phenylalanine to produce trans-cinnamic acid, which is widely used in the fields of pharmacy, food and agriculture. In particular, phenylalanine ammonia lyase from Anabaena variabilis (AvPAL) is the only protein drug for the treatment of phenylketonuria. However, the poor activity and low stability limit the application in industry of AvPAL. In this study, the key amino acids of substrate-binding cavity in AvPAL were identified by screening the single site saturation mutagenesis library. Subsequently, the impact of replacing M222 with the additional 19 amino acids on activity was also evaluated by site-directed mutagenesis. It was found that the k_cat values of mutants M222L and M222V were 90% and 60% higher than that of AvPAL, and the k_cat/K_m was 1.4 and 1.5 times as that of AvPAL. Molecular docking results revealed that the higher activity of M222L and M222V may be due to the increase of hydrophobicity favorable for the substrate-binding cavity. This study is important for elucidating the structure-function relationship of AvPAL.