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 study the effects of Zigui yichong formula on premature ovarian insufficiency （POI） in mice through glycolysis metabolic pathway. METHODS Eighty SPF C57BL/6N female mice were divided into normal group， model group， Zigui yichong formula group （14.175 g/kg）， Zigui yichong formula+2-deoxy-D-arabino-hexose （2-DG） group （Zigui yichong formula 14.175 g/kg + glycolysis inhibitor 2-DG 100 mg/kg）， with 20 mice in each group. Except for the normal group， POI model mice were induced by intraperitoneal administration of cyclophosphamide in the other groups. After the model was successfully established， each group was given corresponding drugs. HE staining was employed to observe the pathomorphological changes in ovarian tissue and to count follicles at all developmental stages； radioimmunoassay was conducted to measure the serum levels of estradiol （E2）， anti-Müllerian hormone （AMH）， and follicle-stimulating hormone （FSH）； TUNEL assay was employed to detect apoptosis in ovarian granulosa cells of mice； the activities of hexokinase （HK）， pyruvate kinase （PK） and lactate dehydrogenase （LDH） were detected by colorimetry； Western blot and real-time fluorescence quantitative PCR were employed to analyze the protein and mRNA expressions of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-3， HK2， pyruvate kinase M2 （PKM2）， and lactate dehydrogenase A （LDHA）. RESULTS Compared with model group， the number of primordial follicles， growing follicles， antral follicles and granulosa cells were increased significantly（P＜0.05）， and granulosa cells arranged neatly， but the number of atretic follicles and granulosa cells apoptosis were decreased significantly in Zigui yichong formula group （P＜0.05）； the serum levels of E2 and AMH， the activities of HK， PK and LDH， protein and mRNA expressions of Bcl-2， HK2， PKM2 and LDHA were increased significantly （P＜0.05）； the serum levels of FSH， the protein and mRNA expressions of Bax and caspase-3， Bax/Bcl-2 ratio were decreased significantly （P＜0.05）. 2-DG could reverse the improvement effects of Zigui yichong formula on the above indexes of POI model mice. CONCLUSIONS Zigui yichong formula may inhibit the apoptosis of ovarian granulosa cells， reduce follicle atresia and improve ovarian reserve function by promoting glycolysis levels in POI model mice.

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 construct a model for predicting early recurrence of hepatocellular carcinoma (HCC) patients after radiofrequency ablation by different machine learning models based on multimodal MRI and clinical indicators, and to evaluate the predictive efficacy of the model.Methods:The data of patients with HCC who underwent radiofrequency ablation in Fourth Medical Center of Chinese PLA General Hospital and the First Medical Center of Chinese PLA General Hospital from January 2015 to December 2021 were retrospectively analyzed. A total of 169 patients with HCC were enrolled, including 152 males and 17 females, aged (57.2±9.2) years. The training set ( n=135) and the test set ( n=34) were randomly divided according to 8∶2. There were 49 cases recurrence in training set and 12 cases recurrence in test set. Based on the training set, the clinical influencing factors of early recurrence in patients with HCC after radiofrequency ablation were screened by univariated and multivariate logistic analysis, and the imaging features were sequentially screened by variance threshold method, select K-best and LASSO regression. Support vector machine (SVM), logistic regression and random forest (RFOREST) were used to construct the prediction models of early postoperative recurrence with simple imagomics alone or combined clinical features, respectively, and the receiver operating characteristic (ROC) curve was used to evaluate the prediction efficiency of the models. Results:Multivariate logistic regression analysis showed that preoperative alpha-fetoprotein >20 μg/L, platelet count >140×10 9 and tumor location were the influential factors for early recurrence of HCC patients after radiofrequency ablation (all P<0.05). Through variance threshold analysis, select K-best and LASSO regression, 16 optimal image omics features were selected. SVM, logistic regression and RFOREST were used to construct a simple imaging omics model for predicting early recurrence of HCC patients after radiofrequency ablation. The areas under ROC curve of the test set were 0.826, 0.830 and 0.826, respectively. And the areas under ROC curve of the constructed imagomics combined clinical model of test set were 0.830, 0.830 and 0.909, respectively. The area under ROC curve of RFOREST in the test set was better than that of SVM and logistic regression ( Z=2.19, 3.98, P=0.008, 0.008). Conclusion:The combined model constructed by SVM, logistic regression and RFOREST based on clinical indicators and image omics features is effective in predicting the early recurrence of patients with HCC after radiofrequency ablation, and the model constructed by RFOREST is the best.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.
Humans ; COVID-19 ; Sleep Initiation and Maintenance Disorders ; Crisis Intervention ; Psychosocial Intervention ; SARS-CoV-2 ; Mental Health ; Depression/epidemiology* ; Health Personnel/psychology* ; Anxiety/etiology*

This paper aimed at studying the effects of hyaluronic acid (HA) with different molecular weights on the transdermal absorption and retention of reduced glutathione (GSH) in the isolated skin of SD rats. Franz diffusion cell method was used to investigate the effects with different molecular weights HA on the in vitro transdermal penetration of GSH and the storage in different layers of the skin. AutoDock molecular docking was used to study the interaction between GSH and HA. Attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR) and H&E section staining were used to characterize the changes and effects of lipids and proteins in the rat stratum corneum after HA acts on the skin. The results of in vitro transdermal experiments showed that HA with different molecular weights had a significant impact on the amount of GSH passing through the skin, that as the molecular weight of HA increased, the effect of preventing GSH from passing through the skin became stronger, that in terms of skin storage, HA with different molecular weights could increase the storage of GSH in the stratum corneum, and that HA with a molecular weight below 7K could also significantly increase the storage of GSH in the dermis. The molecular docking results showed that HA and GSH had a relatively strong interaction, which could form intermolecular hydrogen bonds; and the results of ATR-FTIR and H&E staining showed that HA could interact with lipids and keratins in the stratum corneum of the skin. Such interaction can increase the permeability of the stratum corneum of the drug, however, as a water-soluble GSH, it may be involved in the formation of intermolecular hydrogen bonds with HA. In the structure of HA hydrogel, the amount of GSH drug passing through the intact skin is reduced; but at the same time, this interaction also provides a reservoir for the formation of GSH, thus increasing its storage in the skin. Through comparison of the storage capacity of GSH in the stratum corneum and dermis of the isolated skin due to the increase of HA with different molecular weights, it has been found that the storage capacity of HA with low relative molecular weight is the best.

OBJECTIVE: To provide genetic testing and prenatal diagnosis for a woman with Sheldon-Hall syndrome. METHODS: The woman was subjected to targeted capture and next-generation sequencing for variant of genes associated with skeletal disorders. And the result was verified in her parents and fetus. RESULTS: The woman was found to harbor a c.188G>A variant of the TNNT3 gene, which was also found in her affected mother and the fetus. Her grandmother and grandmother's brother had similar manifestations, which was in line with an autosomal dominant inheritance. The same variant was not found in her father. CONCLUSION The c.188G>A variant of the TNNT3 gene probably underlay the distal joint contracture in this pedigree, based on which prenatal diagnosis was attained.

Objective:To investigate the optic nerve subarachnoid space area (ONSSA) in patients with normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG) and its correlation with related factors.Methods:Fifty-three patients with NTG (Group A) and 46 patients with POAG (Group B) were selected from January 2016 to May 2019 in Gaozhou Traditional Chinese Medicine Hospital of Guangdong Province. None of them received any treatment. Another 40 patients with health examination (Group C) were selected. Body mass index, blood pressure, 24-hour intraocular pressure, visual field damage, visual axis length and central corneal thickness were measured in each group. Two-dimensional ultrasound was performed to analyze the difference of ONSSA in the retrobulbar 3 to 7 mm range in each group, and the correlation between ONSSA and clinical related factors was analyzed.Results:The ONSSA in group A was significantly smaller than that in group B and group C: (5.07 ± 0.83) mm 2 vs. (6.19 ± 0.90) and (6.57 ± 1.43) mm 2, the differences were statistically significant ( t = 5.219 and 6.107, P < 0.05). ONSSA in group A was positively correlated with the mean intraocular pressure and maximum intraocular pressure of 24 hours ( r = 0.658 and 0.479, P < 0.05), while ONSSA in group B and C was not correlated with the mean intraocular pressure and maximum intraocular pressure of 24 hours ( P > 0.05). ONSSA was not correlated with age, body mass index, mean arterial pressure, central corneal thickness, visual field damage and visual axis length ( P > 0.05). Conclusions:ONSSA of NTG patients is lower than that of POAG patients and healthy people, and the ONSSA of NTG patients is correlated with the mean intraocular pressure and maximum intraocular of 24 hours.