Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

Objective:To investigate the clinical value of targeted sequencing panel in the detection of genetic variation in neonates in neonatal intensive care unit (NICU).Methods:All neonates (≤28 d of age) admitted in the NICU (case group) and 200 full-term healthy neonates born with no obvious phenotypic abnormalities of Huzhou Maternity and Child Health Care Hospital were enrolled in this prospective study from November 2022 to January 2023. Based on a list of preventable and treatable rare diseases as well as newly screened diseases in China, a targeted sequencing panel suitable for Chinese newborns was designed to target the pathogenic genes and mutation sites associated with 601 genes and 542 diseases. Dried blood spot specimens were prepared and analyzed by the targeted sequencing panel. Pathogenic sites detected by the panel sequencing were verified using Sanger sequencing. The genetic testing results were analyzed according to the clinical features of the neonates. According to the number of primary clinical diagnosis index (including premature infants, neonatal hyperbilirubinemia, hemorrhagic diseases, neonatal infections, ventricular septal defect/patent ductus arteriosus, and others), these patients were divided into four groups with 1, 2, 3, and ≥4 diagnosis index, respectively. Chi-square test and linear correlation Chi-square test were used for statistical analysis. Results:There were 173 patients in the case group and 30.6% (53/173) of them carried pathogenic variants, including 52 positive for pathogenic genes and one with chromosome copy number variant. The positive rate of pathogenic genes was significantly higher in the case group than in the control group [30.1% (52/173) vs. 15.0% (30/200), χ 2=12.26, P<0.001]. Fourteen pathogenic genes were detected in the case group, including FLG, UGT1A1, G6PD, MYH7, AR, ABCC2, ACADS, CYP21A2, GJB2, MEFV, PAH, PKHD1, SCN4A, and HBA. In the case group, the detection rate of pathogenic variants in jaundiced neonates was higher than that in non-jaundiced neonates [35.2% (44/125) vs. 18.8% (9/48), χ 2=4.42, P=0.036]. However, there were no statistically significant differences in the detection rates of pathogenic variants between male and female infants, infants born to mothers of advanced maternal age or not, infants born to mothers with or without gestational diabetes mellitus, premature and term infants, or infants with or without hemorrhagic disorders, neonatal infections, or ventricular septal defects/patent ductus arteriosus in the case group (all P>0.05). The detection rate of pathogenic variants showed a linear increase in infants with 1, 2, 3, and ≥4 diagnosis index [21.1% (8/38), 25.4% (15/59), 38.2% (13/34), and 40.5% (17/42); linear correlation χ 2=4.84, P=0.028]. In the case group, seven genes with a high detection rate of genetic variation (including positive pathogenic genes and carriers) were UGT1A1 [had the highest detection rate, 24.9% (43/173)], GJB2, FLG, DUOX2, ABCA4, G6PD, and MUT. Seven loci with higher mutation frequency were c.211G>A(p.Gly71Arg), c.1091C>T(p.Pro364Leu), c.-41_-40dupTA, and c.686C>A(p.Pro229Gln) in the UGT1A1 gene, c.109G>A(p.Val37Ile) in the GJB2 gene, and c.12064A>T(p.Lys4022Ter) and c.3321del(p.Gly1109GlufsTer13) in the FLG gene. Conclusion:This panel sequencing can provide effective genetic testing for neonates in NICU, especially in children with complex clinical diagnosis.

Objective:To analyze the types and distribution of pathogenic variants for neonatal genetic diseases in Huzhou, Zhejiang Province.Methods:One thousand neonates (48 ~ 42 h after birth) born to Huzhou region were selected as the study subjects. Dry blood spot samples were collected from the newborns, and targeted capture high-throughput sequencing was carried out for pathogenic genes underlying 542 inherited diseases. Candidate variants were verified by Sanger sequencing.Results:Among the 1 000 newborns, the male to female ratio was 1.02 : 1.00. No pathogenic variants were detected in 253 cases, whilst 747 cases were found to carry at least one pathogenic variant, which yielded a carrier rate of 74.7%. The most frequently involved pathogenic gene was FLG, followed by GJB2, UGT1A1, USH2A and DUOX2. The variants were classified as homozygous, compound heterozygous, and hemizygous variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), 213 neonates were verified to have carried pathogenic and/or likely pathogenic variants, with a positive rate of 21.3%. The most commonly involved genes had included UGT1A1, FLG, GJB2, MEFV and G6PD. Conclusion:Newborn screening based on high-throughput sequencing technology can expand the scope of screening and improve the positive predictive value. Genetic counseling based on the results can improve the patients′ medical care and reduce neonatal mortality and childhood morbidity, while provide assistance to family members′ health management and reproductive decisions.

Objective:To investigate the status quo of anticoagulant therapy for patients with non-valvular atrial fibrillation (NVAF) in Beijing community health centers and to analyze the affecting factors.Methods:From September to December 2020, 164 patients with NVAF in five community health service centers in Xicheng District of Beijing were selected for a face-to-face questionnaire survey. The questionnaire included basic information of patients, complications, CHA 2DS 2-VASc score, HAS-BLED score and oral anticoagulant therapy, et al. SPSS 23.0 software was used to analyze the status of anticoagulant therapy in patients with different risk stratification of stroke, and chi-square was used to analyze the factors affecting anticoagulant therapy in high-risk patients with stroke. Results:In 161 NVAF patients with indication, 86 received anticoagulation therapy (53.4%), and the utilization rates of rivaroxaban, dabigatran and warfarin were 64.0% (55/86), 26.7% (23/86) and 9.3% (8/86), respectively. In 140 patients (85.4%, 140/164) at high risk of stroke (CHA 2DS 2-VASc score ≥2 points in males or ≥3 points in females), 30.0% (42/140) had never received anticoagulant therapy, and 29.3% (41/140) was treated with antiplatelet therapy, 17.1% (24/140) did not use any antithrombotic medication. Univariate analysis showed that gender, age, symptoms at first diagnosis and complications were not significantly associated with the application of anticoagulant therapy in NVAF patients at high-risk of stoke ( P>0.05). The qualitative study showed that the reasons for not receiving anticoagulant therapy were spontaneous cardioversion or recovery of sinus rhythm after ablation (15 cases), adverse drug reactions (7 cases), self-withdrawal of drugs (10 cases), concern about bleeding (3 cases) and so on. Conclusion:A large proportion of NVAF patients in the community are at high risk of stroke, while the overall rate of anticoagulant treatment is relatively low. Clinician in the community should actively initiate anticoagulant therapy for patients with AF and strengthen the continuous management and compliance management of anticoagulant therapy.

Objective:To investigate the knowledge status and health education needs of patients with atrial fibrillation in the community.Methods:From September to December 2020, 277 patients with atrial fibrillation from 5 community health service centers in Xicheng District of Beijing were selected using typical sampling method for online questionnaire survey. The questionnaire mainly contained basic information of patients, the knowledge of atrial fibrillation and the health education needs. Factors affecting patients′ knowledge level and health education needs were analyzed.Results:The overall awareness rate of disease-related knowledge in 277 patients with atrial fibrillation was 67.1% (1 860/2 770), and in aspects of antithrombotic effect of aspirin [12.3% (34/277)], the benefits and risks of anticoagulation therapy [52.7% (146/277)] and atrial fibrillation discontinuation [55.2% (153/277)], the awareness rates were relatively low. Compared with patients in the age group of 66-79 years and ≥80 years old, those aged ≤65 years had higher awareness rates in knowledge of purpose of anticoagulantion therapy [89.7% (70/78)] and adverse reactions of anticoagulation drugs [89.7% (70/78)] (χ2=6.72, 8.77; P<0.05), but the awareness rate of the benefits and harms of anticoagulation therapy [43.6% (34/78)] was lower (χ2=6.11, P<0.05). The top three health education needs of patients were the impact of atrial fibrillation on the body (3.66±1.77), the method of treating atrial fibrillation (3.65±1.13) and the prognosis with different treatments (3.62±1.15). Further analysis showed that in patients with disease duration ≤5 years, the education needs for the purpose of anticoagulation therapy (3.60±1.17), exercise methods (3.62±1.12), dietary taboos (3.63±1.16), and how to communicate with family and friends(3.33±1.29) were higher than those with a disease duration of more than 5 years ( t=2.03, 2.88, 2.05, 2.07; P<0.05). Doctors [98.6% (273/277)], nurses [40.8% (113/277)] and health education lectures [36.8% (102/277)] were the main sources for patients to acquire knowledge about atrial fibrillation. Most patients had the strongest motivation to obtain health education at the time of disease diagnosis [70.0% (194/277)]. Conclusions:There is insufficient understanding of the disease in patients with atrial fibrillation in the community, and the needs for patients to get health education are high. It is necessary to pay more attention to the early health education in patients with younger age and shorter course of disease.

Objective:To evaluate the prognostic efficacy of the Chinese Group on the Study of Severe Hepatitis B (COSSH) acute-on-chronic liver failure (ACLF) II score (COSSH ACLF IIs) and associated risk stratification in predicting short-term prognosis of patients with hepatitis B virus-related ACLF (HBV-ACLF).Methods:Clinical data of 224 patients with HBV-ACLF admitted to the First Affiliated Hospital of Wannan Medical College and the First Hospital of Quanzhou, Fujian Medical University from January 2018 to December 2021 were retrospectively analyzed. The patients were divided into survival group ( n=171) and fatal group ( n=53) according to 28-day survival status. The values of the COSSH ACLF IIs, the Chronic Liver Failure-Consortium (CLIF-C) ACLF score (CLIF-C ACLFs), the CLIF-C organ failure score (CLIF-C OFs), the Model of End-stage Liver Disease (MELD) score (MELDs), the MELD-sodium score (MELD-Nas), and the Child-Turcotte-Pugh score (CTPs) for 28-day mortality prediction were compared using the area under the receiver operating characteristic curve (AUC). The patients were divided into groups according to COSSH ACLF classification and COSSH ACLF IIs risk stratification, respectively. The differences in 28-day mortality between groups were compared by Kaplan-Meir method, and the consistency of the two ACLF classification systems was compared by Kappa consistency test. Results:The AUC, sensitivity, and specificity of the COSSH ACLF IIs in 28-day mortality prediction were 0.885, 0.981 and 0.731, respectively. For predicting 28-day mortality, the COSSH ACLF IIs achieved a higher AUC than the CLIF-C OFs, the MELDs, the MELD-Nas, and the CTPs ( P<0.01), while there was no significant difference in AUC between the COSSH ACLF IIs and the CLIF-C ACLFs ( Z=1.696, P=0.090). The cumulative 28-day mortality rates significantly increased with the ascending of COSSH ACLF grade and risk strata of the COSSH ACLF IIs (11.7%, 43.5% and 93.3%, P<0.001; 14.2%, 41.0% and 81.3%, P<0.001). The two ACLF grading systems showed a consistency in severity stratification of HBV-ACLF patients (Kappa=0.478, P<0.001). Conclusion:The COSSH ACLF IIs shows an excellent prognostic performance in predicting short-term mortality of HBV-ACLF patients. Using the new risk stratification scale can simplify the severity stratification of HBV-ACLF patients.

Objective:To investigate the change of the detection rate of colorectal cancer (CRC), colorectal adenoma and advanced adenoma in adults under colonoscopy in Shihezi in the past ten years.Methods:Data of patients who completed colonoscopy in the First Affiliated Hospital of Shihezi University School of Medicine from January 1, 2010 to December 31, 2019 were investigated. The medical records were collected by consulting the electronic medical record system, including the age and sex of patients and the location, quantity, size and pathological type of lesions. The detection rates, including the overall detection rate in the past 10 years, those in the first 5 years (from 2010 to 2014) and the second 5 years (from 2015 to 2019) of colorectal adenomas, advanced colorectal adenomas and CRC, were studied.Results:A total of 50 645 cases were included, 14 931 cases were excluded by the exclusion criteria, and finally a total of 35 714 cases were included in the data analysis. The 10-year overall detection rates of colorectal adenoma, advanced colorectal adenoma and CRC were 17.65% (6 302/35 714), 4.45% (1 589/35 714) and 3.71% (1 324/35 714), respectively. The overall detection rates of colorectal adenoma and advanced colorectal adenoma in the second 5 years were higher respectively than those in the first 5 years [20.33% (4 565/22 457) VS 13.10% (1 737/13 257), 4.69% (1 053/22 457) VS 4.04% (536/13 257)]. The overall detection rate of CRC in the second 5 years [3.30% (741/22 457)] was lower than that in the first 5 years [4.40% (583/13 257)].Conclusion:Compared with 2010 to 2014, the detection rate of colorectal adenoma in Shihezi area in 2015 to 2019 increased significantly, the detection rate of advanced colorectal adenoma increased slightly, and the detection rate of CRC decreased slightly. Therefore, the detection and resection of colorectal adenoma by colonoscopy may be important in reducing the incidence of CRC.

Objective:To observe the recovery of exercise tolerance among stroke survivors using the cardiopulmonary exercise test (CPET) and analyze the factors influencing it.Methods:A total of 81 stroke survivors hospitalized in the Department of Rehabilitation Medicine of our hospital in year 2018 and 2019 were selected. The general clinical data of all patients were collected retrospectively and combined with the data from CPET to establish a data set. Version 25.0 of the SPSS software was used for multiple linear regressions analysis, with the peak oxygen uptake as the dependent variable, and the age, Brunnstrom stage, peak power, peak heart rate, peak respiratory exchange ratio, peak breathing reserve, peak ventilation per minute, the slope of the VE-VCO 2 curve (ΔVE/ΔVCO 2) and peak end tidal partial pressure of carbon dioxide as independent variables. Results:Stroke survivors at Brunnstrom stage III Ⅲ, Ⅳ and Ⅴ or higher decreased sequentially with their age, but their peak oxygen uptake increased gradually. The multiple linear regression model constructed by " stepwise method" showed that the fitted multiple linear regression equation was statistically significant ( F=100.228, P<0.001). Moreover, the average peak power, peak heart rate, peak ventilation per minute and the slope of the VE-VCO 2 curve were all found to be significant independent predictors of peak oxygen uptake in these stroke survivors. Conclusions:Skeletal muscle power, cardiac function, pulmonary ventilation and ventilation efficiency are useful independent predictors of the exercise tolerance of stroke survivors.

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

Objective To investigate any protective effect of low-intensity pulsed ultrasound (LIPUS) and pioglitazone on chondrocytes in osteoarthritic patients using the pathway from peroxisome proliferator-activated γreceptor (PPARγ) to nuclear factor kappa B (NF-κB) to inducible nitric oxide synthase (iNOS).Methods Normal chondrocytes of 24 healthy adult New Zealand white rabbits were extracted and divided into a normal group,a lipopolysaccharide (LPS) group,a LIPUS group (LPS+LIPUS) and a pioglitazone group (LPS+pioglitazone),each of 6 using a random number table.Each group was given the intervention their names implies.The levels of tumor necrosis factor-α (TNF-α),leptin (LEP) and nitric oxide (NO) in the chondrocytes were detected using enzyme-linked immune sorbent assays.The expression of type Ⅱ collagen (COL2) in the chondrocytes of each groups was detected using immunocytochemistry and fluorescent staining.The mRNA and protein expressions of PPARγ,NF-κB and iNOS were detected using reverse transcription polymerase chain reactions and western blotting respectively.Results Compared with the LPS group,the average level of TNF-α,LEP and NO in the LIPUS and pioglitazone groups was significantly lower,with the levels in the pioglitazone group significantly lower than in the LIPUS group.Compared with the LPS group,COL2 expression in the LIPUS group was significantly greater.The mRNA and protein expressions of PPARγ in the chondrocytes in the LIPUS and pioglitazone groups were significantly higher than those in the LPS group.Compared with the LPS group,the mRNA and protein expressions of NF-κB and iNOS in the pioglitazone and LIPUS groups were significantly lower,with the pioglitazone group's levels significantly below those of the LIPUS group.Conclusion LIPUS and pioglitazone may promote anti-inflammatory action and COL2 synthesis in chondrocytes through the PPARγ/ NF-κB/iNOS pathway and play a protective role,at least in rabbits.