ObjectiveTo investigate the material basis of the pathogenesis of cerebral ischemic injury with blood stasis and toxin syndrome and to explore the protective effects of Huayu Jiedu prescription （HYJDP） on neutrophil extracellular trap-related cell death （NETosis） in cerebral ischemic injury following acute cerebral infarction. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly divided into six groups （n=12 per group）： sham operation （Sham） group， blood stasis and toxin model （Model） group， low-， medium-， and high-dose HYJDP groups （HYJDP-L， HYJDP-M， and HYJDP-H； 9， 18， and 36 g·kg^-1， respectively）， and butylphthalide （NBP） group （0.06 g·kg^-1）. Except for the Sham group， rats in all other groups were subjected to carrageenan/dry yeast combined with a modified intraluminal filament method to establish a focal cerebral ischemia model of the middle cerebral artery with blood stasis and toxin syndrome. Neurological function was evaluated at 24 h after modeling using the Zea-Longa neurological deficit score. Cerebral infarction rate was assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Pathological morphology of brain tissue was observed using hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of interleukin-8 （IL-8）， myeloperoxidase-DNA complexes （MPO-DNA）， and citrullinated histone H3 （CitH3）. Protein expression of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （p-Akt）， mammalian target of rapamycin （p-mTOR）， sequestosome 1 （p62）， and CitH3 in brain tissue was detected by Western blot. Immunofluorescence （IF） was used to detect the expression of neutrophil-specific marker Ly6G， CitH3， and neuron-specific nuclear protein （NeuN） in brain tissue. ResultsCompared with the Sham group， neurological deficit scores and cerebral infarction rates in the model group were significantly increased （P<0.01 for both）. HE staining showed varying degrees of neuronal degeneration and necrosis， characterized by blurred neuronal structures， nuclear pyknosis and fragmentation， cytoplasmic dissolution into a vacuolated reticular pattern， and mild glial cell proliferation. ELISA results showed that serum levels of IL-8， MPO-DNA， and CitH3 were significantly increased （P<0.01）. Western blot analysis demonstrated decreased expression of p-PI3K， p-Akt， p-mTOR， and p62， while CitH3 expression was significantly increased （P<0.01）. IF results showed an increased number of NETs⁺ cells and a significant decrease in NeuN⁺ cells （P<0.01）. Compared with the Model group， neurological deficit scores in the HYJDP-H group were significantly decreased （P<0.05）， and cerebral infarction rates in the HYJDP-H and NBP groups were significantly reduced （P<0.01）. HE staining showed that brain tissue damage was markedly alleviated in the HYJDP-H group. ELISA results showed that levels of IL-8， MPO-DNA， and CitH3 were significantly decreased in the HYJDP-M， HYJDP-H， and NBP groups （P<0.01）. Western blot analysis showed that expression of p-PI3K， p-Akt， p-mTOR， and p62 was significantly increased in the HYJDP-H and NBP groups， while CitH3 expression was significantly reduced in all drug intervention groups （P<0.01）. IF results showed that the number of NETs⁺ cells was significantly decreased and the number of NeuN⁺ cells was significantly increased in all drug intervention groups （P<0.01）. ConclusionNETs may be the material basis of the pathogenesis of cerebral ischemic injury characterized by blood stasis and toxin. HYJDP can regulate the PI3K/Akt/mTOR signaling pathway， reduce the release of pro-inflammatory mediators and NETosis-related products， alleviate cerebral ischemic injury caused by autophagy-dependent NETosis， and thereby exert a neuroprotective effect.

[Objective] To analyze the infection status of hepatitis E virus (HEV) among blood donors in Zhengzhou, so as to provide data support for formulating local blood screening strategies. [Methods] Random samples from blood donors from January to December 2022 were tested for HEV RNA using PCR technology. Reactive samples were sequenced for gene analysis, and the donors were followed up. [Results] Among 21 311 samples, 3(0.14‰) were reactive for HEV RNA, all of whom were male. Genetic sequencing results revealed that one strong positive sample was genotype 4, while sequencing failed for the other two due to low viral load. A follow-up of 25 strong positive donors showed that ALT significantly increased on day 7 after donation, anti-HEV IgM and anti-HEV IgG turned positive. On day 21, ALT returned to normal, and on day 35, HEV RNA turned negative. Notably, anti-HEV IgM and anti-HEV IgG persisted until day 482. [Conclusion] There is HEV infection among blood donors in Zhengzhou, and it is necessary to expand the screening scope to comprehensively explore the prevalence and genotype distribution of HEV among blood donors.

Chronic liver diseases with common causes including viral infections， alcohol abuse， and autoimmune diseases. Alkaloids， as a class of plant-derived compounds， have shown significant potential in regulating chronic liver diseases. Recent studies have shown that alkaloids are able to exert a therapeutic effect on chronic liver diseases through multiple pathways. These compounds have a regulatory effect on key pathological processes such as liver fibrosis， inflammatory response， oxidative stress， and cell apoptosis， and they also regulate the metabolic homeostasis of hepatocytes by modulating multiple signaling pathways， thereby playing a role in regulating chronic liver diseases. This article reviews the role and mechanism of alkaloids in the treatment of chronic liver diseases， in order to provide new ideas and directions for the treatment of chronic liver diseases.

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

Objective To analyze the research trends and frontier of TCM regulation of NF-κB;To provide reference for related research.Methods Relevant literature about TCM regulation of NF-κB was retrieved from CNKI,VIP,Wanfang Data,CBM and Web of Science from January 1,2013 to December 31,2022.VOSviewer 1.6.19 and CiteSpace 6.2.R4 software were used for visualization analysis on authors,institutions and keywords.Results Totally 3 728 articles in Chinese and 995 in English were included,and the number of articles was on the rise.The Chinese and English articles involved 487 and 237 core authors,respectively,forming research teams represented by Yan Guanghai,Liu Jian,Wang Li,and Li Wei,Zhang Li,Zhang Yu,etc.There were 7 and 8 effective clusters in Chinese and English articles respectively.Keyword analysis showed that this research field mainly focused on diseases(inflammatory diseases,tumors,cardiovascular and cerebrovascular diseases,etc.),research methods(in vivo experiment,in vitro experiment)and intervention methods(acupuncture,TCM monomer,TCM compound,etc.).Conclusion TCM regulation of NF-κB mainly focuses on related diseases and intervention methods,and it is a research trend to find drug action targets and conduct experimental verification through network pharmacology and molecular docking technology.

Objective:To evaluate the effectiveness and safety of mesenchymal stem cells (MSCs) in the treatment of knee osteoarthritis (KOA).Methods:The databases PubMed, OVID, Web of Science, CNKI, Wanfang, were systematically searched from inception to May 2023 to collect randomized control trials(RCTs) of MSCs in the treatment of KOA. The literature was selected according to the inclusion and exclusion criteria, and relevant data was extracted. Meta-analysis was conducted using RevMan 5.4 software. Heterogeneity was assessed using the I2 statistic, with the fixed effects model applied when I2 was less than 50%, and the random effects model utilized otherwise. The combined effect size and 95% confidence interval ( CI) were calculated using the inverse-variance method. Sensitivity analysis and assessment of publication bias were performed using Stata 14.0 software. Results:A total of 29 RCTs involving 1 402 participants were included. The outcomes showed that at the 12 month follow-up, MSCs reduced pain [WOMAC pain: MD(95% CI)=-4.38(-7.22, -1.55), P<0.001; VAS: MD(95% CI)=-2.00(-2.67, -1.33), P<0.001 ]. And WOMAC stiffness[WOMAC stiffness:MD(95% CI)=-1.21(-2.32, -0.10), P<0.001]; moreover, MSCs reduced KOA severity and Restored joint function, [WOMAC: MD(95% CI)=-9.40(-15.87,-2.93), P<0.001; Lequesne: MD(95% CI)=-10.57(-15.89, -5.24), P<0.001 ].And the effect lasted for at least 4 years. MRI analysis showed no significant difference between the MSC group and the control group [MD(95% CI)=-6.68 (-18.45, 5.09), P=0.270]. Subgroup analysis showed that there was no significant difference in the effects of the tissue source and dosage of MSC on osteoarthritis pain and joint function. Using WOMRS for subgroup analysis, we found that adipose tissue was the best MSCs source for cartilage repair in osteoarthritis [MD (95% CI) =-30.94(-43.87, -18.01), P<0.001]. For the occurrence of adverse events, no study had reported the occurrence of serious adverse events. Most of the adverse events were self-limited pain and discomfort, such as transient joint swelling and back pain. Conclusion:Based on current evidence, MSCs may be a safety therapy that have a good effect for OA, and the time to maintain the curative effect is no less than 4 years. There is currently no reliable evidence to address the issue of which tissue source and injection cell dosage yield the best therapeutic effect. High-quality clinical trials are needed.

【Objective】 To investigate the clinical characteristics, long-term follow-up rate, level and control rate of low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) aged ≥75 years who underwent percutaneous coronary intervention (PCI) during hospitalization. 【Methods】 We selected ASCVD patients aged ≥75 years with PCI from January 2016 to December 2020 in The First Affiliated Hospital of Xi’an Jiaotong University, collected the baseline data of the patients and the follow-up of 1 month, 3 months, 6 months and 12 months after discharge by HIS system, and analyzed their LDL-C and control rate at each follow-up. 【Results】 A total of 1 129 patients were enrolled in this study, aged 78 (ranging from 75 to 89) years. Among them 72.1% were male; myocardial infarction was the main type of ASCVD (71.5% ); hypertension was the most common risk factor, accounting for 85.2% (717/842), followed by diabetes, 58.6% (493/842); 74.6% met the ultra-high risk criteria of the 2020 Chinese Expert Consensus on Lipid Management in Ultra-High Risk ASCVD Patients, and the LDL-C control rate was only 8.1% . The four routine follow-up rates of 1 129 elderly ASCVD patients were 49.5%, 24.1%, 17.1%, and 24.6%, respectively. The detection rates of LDL-C during follow-up were 26.3%, 5.3%, 10.4%, and 13.8%, respectively. LDL-C control rates in ultra-high risk ASCVD were 59.4%, 45.1%, 37.1%, and 17.6%, respectively, while LDL-C control rates in non-ultra-high risk ASCVD patients were 67.3%, 55.6%, 47.4%, and 44.0%, respectively. 【Conclusion】 The elderly patients with ASCVD-PCI were mainly ultra-high risk patients. The routine follow-up rate and the LDL-C compliance rate during follow-up were low and showed a downward trend.

We reported the clinical data of a neonate admitted to the Second Affiliated Hospital (Yuying Children's Hospital) of Wenzhou Medical University in November 2021 with autosomal recessive complete signal transducer and activator of transcription 1 ( STAT1) deficiency identified by whole exome sequencing. The baby boy received bacillus of calmette-guerin (BCG) vaccine 2 d after birth and presented with persistent high fever, increased white blood cell count and increased level of C-reactive protein (CRP) on 21 d after birth. Human cytomegalovirus (HCMV) was detected in both blood and bone marrow specimens. The patient improved after comprehensive treatment with antiviral agents, antibiotics and intravenous gammaglobulin. Oral anti-viral drugs were prescribed on discharge. However, the baby was rehospitalized due to a fever at 55 days. HCMV and Mycobacterium tuberculosis complex were detected in blood samples. The infant was transferred to the Children's Hospital of Fudan University due to persistent high fever even after active management and died after treatment withdrawal at 69 d after birth because of worsening infections and multiple organ failure. A homozygous mutation in the STAT1 gene was detected [c.1011_1012del, NM_007315: exon11: c.1011_1012del (p.V339Pfs*18)] and the child was diagnosed as autosomal recessive complete STAT1 deficiency. We concluded that the clinical manifestations of autosomal recessive complete STAT1 deficiency are bacterial infections caused by lethal low-pathogenic mycobacteria and life-threatening virus infections. Whole exome sequencing is of great value for early diagnosis and timely treatment. The prognosis of this disease is very poor, but the condition of the patients might be improved in a short period with early anti-tuberculosis and anti-viral treatment.

Objective:To summarize the clinical characteristics and genetic etiology of infants with D-bifunctional protein deficiency (DBPD).Methods:This study involved two DBPD newborns who were hospitalized in the Second Affiliated Hospital of Wenzhou Medical University in August 2020 and November 2020. Clinical data including manifestations, radiographic findings and genetic testing results were retrospectively analyzed. Relevant articles up to November 2022 were retrieved from various databases including CNKI, Wanfang, CQVIP, Online Mendelian Inheritance in Man and PubMed using the terms of "D-bifunctional protein deficiency" and " HSD17B4" in both Chinese and English. Clinical data of the cases diagnosed with DBPD by genetic testing within two years of age were collected. Clinical features and genetic etiology of the children with DBPD were summarized by descriptive statistical analysis. Results:Both neonates in this report presented with dyspnea, hypotonia, intractable epilepsy, poor response, absence of primitive reflexes, and craniofacial malformation. Whole-exome sequencing revealed that patient 1 carried heterozygous variations of c.972+1G>T and c.727T>A (p.W243R) in the HSD17B4 gene, which were inherited from his father and mother, respectively. A homozygous variation of c.1333+4A>G in the HSD17B4 gene was identified in patient 2. All these mutations were pathogenic. Thirteen papers (12 in English and one in Chinese) involving 19 patients from 16 pedigrees were retrieved. Altogether 21 patients (eight males and 13 females) were included, and among them, four from two pedigrees were born to consanguineous parents. There were 21 patients with hypotonia, 20 with epileptic seizures (17 presenting with epileptic seizures within 5 d after birth) and 12 with craniofacial deformities including high forehead, long philtrum and high palatine arches. Genetic tests showed that 13 patients carried compound heterozygous variations in the HSD17B4 gene and eight patients had homozygous variations. Twenty-six variations in the HSD17B4 gene were detected, including 16 missense mutations, seven splicing mutations, two nonsense mutations and one frameshift mutation. Conclusion:DBPD should be considered and genetic tests should be given when newborns have dystonia and intractable epilepsy complicated by appearance deformity.

OBJECTIVE: To investigate the short- and mid-term effectiveness of unicompartmental knee arthroplasty (UKA) for post-traumatic arthritis (PTA) of knee. METHODS: The clinical data of 30 patients with PTA of unilateral knee between March 2014 and September 2021 was retrospectively analyzed. There were 14 males and 16 females with an average of 64.5 years (range, 33-81 years). The average body mass index was 26.7 kg/m ² (range, 19.8-35.6 kg/m ²). The types of injuries that caused PTA included intra-articular fracture in 16 cases, extra-articular fracture in 8 cases, and soft tissue injury in 6 cases. The initial injuries were treated by conservative therapy in 12 cases and by surgical therapy in 18 cases. Ten cases were medial compartment osteoarthritis and 20 cases were lateral compartment osteoarthritis. According to Kellgren-Lawrence staging, there were 19 cases of grade Ⅲ and 11 cases of grade Ⅳ. The operative time, the length of hospital stay, complications, and subjective satisfaction were recorded. The Oxford Knee Function Score (OKS), Hospital for Special Surgery (HSS) score, and knee range of motion (ROM) were used to evaluate knee function. Weight-bearing X-ray films were taken to measure the femoro-tibial angle (FTA) and to assess alignment correction of the lower limb. RESULTS: The operative time ranged from 50 to 95 minutes (mean, 63.7 minutes), the length of hospital stay ranged from 3 to 8 days (mean, 6.9 days). Superficial infection occurred in 2 patients, while the remaining incisions healed by first intention. There was no deep vein thrombosis or neurovascular injury. All patients were followed up 17-109 months (median, 70 months). At last follow-up, OKS score, HSS score, and ROM in 30 cases significantly improved when compared with those before operation (P<0.05). Lower limb alignment was significantly corrected and there was significant difference in FTA of the varus and valgus knees between pre- and post-operation ( P<0.05). The patient satisfaction rate was 86.7% (26/30). Two cases developed contralateral osteoarthritis progression during follow-up. No bearing dislocation, prosthesis loosening or sinking occurred and none required further revision. CONCLUSION For patients with PTA of knee, UKA can obtain definite short- and mid-term effectiveness with high patient satisfaction.
Male ; Female ; Humans ; Arthroplasty, Replacement, Knee ; Retrospective Studies ; Knee Prosthesis ; Osteoarthritis, Knee/surgery* ; Treatment Outcome ; Knee Joint/surgery* ; Lower Extremity/surgery* ; Range of Motion, Articular