ObjectiveTo investigate the role and mechanism of Go-Ichi-Ni-San complex subunit 1 （GINS1） in the progression of hepatocellular carcinoma （HCC） and the development of chemotherapy resistance. MethodsThe tumor database GEPIA2 was used to analyze the differential expression of GINS1 between HCC patients and healthy individuals， and pathological tissue samples were collected from 40 HCC patients who were admitted to The Affiliated Tumor Hospital of Xinjiang Medical University and the First Affiliated Hospital of Xinjiang Medical University from May 2017 to January 2021. Immunohistochemical staining was used to measure the difference in the expression of GINS1 between HCC tissue and corresponding adjacent tissue， and the correlation between the expression level of GINS1 and the clinical TNM stage of HCC was analyzed. Western blot was also used to measure the difference in the expression of GINS1 between HCC Huh7/Hep3B/Li-7/MHCC97H cell lines and normal human QSG7701 hepatocytes. The method of lentivirus transfection was used to establish the MHCC97H cell line with stable GINS1 knockdown and its negative control cell line. CCK-8 assay and colony formation assay were used to measure cell proliferative capacity； scratch assay was used to measure cell migration ability； Transwell assay was used to measure cell invasion ability； cells were treated with oxaliplatin to measure their sensitivity to chemotherapy drugs. Nude mice were used to establish a tumor-bearing model and observe the effect of GINS1 knockdown on the growth of HCC in vivo. Western Blot was used to measure the expression levels of the proteins associated with the Notch pathway and the JAK/STAT pathway. The cells were treated with the Notch receptor agonist Jagged-1 to analyze the association between GINS1 and the Notch/JAK/STAT pathway. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe expression of GINS1 was upregulated in HCC patients， HCC tissue， and HCC cell lines （all P<0.05）， and the expression level of GINS1 was positively correlated with the clinical TNM stage of HCC （r=0.822， P=0.011）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in proliferation， migration， and invasion activities （all P<0.01） and a significantly enhanced sensitivity to oxaliplatin （P<0.01）. Compared with the nude mice in the control group， GINS1 knockdown caused significant inhibition of tumor weight and volume in vivo in nude mice （all P<0.001）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in the expression levels of Notch1， Notch3， p-JAK2， and p-STAT3 （all P<0.05）， while there were no significant differences in the overall expression levels of JAK2 and STAT3 （P>0.05）. After Jagged-1 treatment， the GINS1-knockdown MHCC97H cells showed significant increases in proliferation， migration， and invasion activities and a significant reduction in sensitivity to oxaliplatin， as well as significant increases in the levels of p-JAK2 and p-STAT3 （all P<0.05）. ConclusionGINS1 is upregulated in HCC and can promote HCC progression and chemotherapy resistance through the Notch/JAK2/STAT3 pathway.

Background Indoor air quality directly affects people's health, especially the impact of chemical pollutants in residential indoor air on children and the elderly is more significant. Objective To understand the pollution status of common chemical pollutants in residential indoor air in Shijiazhuang, evaluate the health risks of chemical pollutants to school-age children and the elderly, and provide reference for controlling indoor pollution in residential environment. Methods Using stratified random sampling, a total of 60 households were selected from 2 urban areas and 1 surrounding rural area in Shijiazhuang City, specifically in July 2023 (non-heating season) and December 2023 (heating season), respectively. Relevant data was collected through on-site sampling [including CO, CO₂, PM₁₀, PM_2.5, NO₂, SO₂, O₃, ammonia, formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOC), trichloroethylene, and tetrachloroethylene] and survey questionnaires. The pollutant concentrations were evaluated following the Standards for indoor air quality of GB/T 18883-2022, and the inhalation exposure risks of the target population were assessed based on the health risk assessment method. Results In the indoor air of the urban and rural residence in Shijiazhuang City, except for CO, NO₂, SO₂, toluene, and xylene, which did not exceed the standard limits, other pollutants showed varying degrees of exceedance. The non-qualified rates of PM₁₀, PM_2.5, and CO₂ in the urban areas were higher than those in the rural areas (P < 0.05). The seasonal difference analysis showed that the non-qualified rates of PM_2.5, PM₁₀, CO₂, trichloroethylene, and tetrachloroethylene in the urban areas were higher in the heating season than in the non-heating season (P<0.05); the non-qualified rates of ammonia and formaldehyde in the rural areas increased significantly in the non-heating season(P<0.05). The health risk assessment indicated that the maximum hazard quotient (HQ) of tetrachloroethylene for the elderly exceeded 1, while the HQ values for ammonia, formaldehyde, benzene, toluene, xylene, and trichloroethylene remained below 1 for either children or the elderly. For carcinogenic risks, the median carcinogenic risk (CR) of formaldehyde for school-aged children or the elderly fell within the range of 10⁻⁶-10⁻⁴, whereas the median CR values for benzene, trichloroethylene, and tetrachloroethylene were all below 10⁻⁶. Conclusion The primary indoor air pollutants exceeding the national standard limits in residential areas of Shijiazhuang City include CO₂, PM₁₀, TVOC, PM_2.5, formaldehyde, ammonia, trichloroethylene, and tetrachloroethylene. The levels of these pollutants exhibit significant urban-rural and seasonal variations. Special attention should be paid to the non-carcinogenic risk of tetrachloroethylene to the elderly and the carcinogenic risks of formaldehyde to school-age children and the elderly.

OBJECTIVE To construct the drug utilization evaluation criteria for Dezocine injection， so as to provide reference for the rational drug use in medical institutions. METHODS On the basis of evidence methodology， relevant guidelines/expert consensus， systematic reviews/meta-analysis were consulted； the evaluation criteria framework for Dezocine injection was established after screening evidence. Delphi method was employed， whereby 28 clinicians and clinical pharmacists from secondary and above-level medical institutions across eight provinces， including Tianjin， Beijing and Shandong， were selected to participate in two rounds of questionnaire surveys. The final indicators were determined based on the experts’ enthusiasm coefficient， authority coefficient， and degree of coordination. RESULTS The effective recovery rate of questionnaire was 100% in the first round and 92.86% in the second round； expert authority coefficient was 0.82 in the first round and 0.81 in the second round； the coordination degree of experts in the first round was 0.29， and in the second round was 0.31 （P＜0.001）. Drug utilization evaluation standard system for Dezocine injection was formed finally， including three dimensions of medication indications， medication process and medication results， with a total of 11 first-level indicators （such as indications， usage and dosage） and 33 second-level indicators （such as labor analgesia and the management of severe pain following major or moderate surgeries combined with other analgesic drugs）. The average importance scores for each indicator ranged from 4.08 to 5.00 points， with an overall average score of 4.61 points and coefficient of variation ranging from 0 to 0.19. CONCLUSIONS The drug utilization evaluation criteria for Dezocine injection established based on evidence-based methodology and Delphi method is authoritative and scientific， which provides a reference for subsequent evaluation of the rationality of clinical medication.

Hepatitis C virus infection is a global public health issue， and the emergence of direct-acting antiviral agents has brought revolutionary breakthroughs in the treatment of hepatitis C patients. Although direct-acting antiviral agents have a marked therapeutic effect in adult patients， there are still many challenges in the treatment of special populations such as pregnant women， infants， young children， and adolescents. This article reviews the current status of antiviral therapy for these special populations with hepatitis C and the problems that need to be solved， in order to provide reference and guidance for clinical workers.

Objective To systematically evaluate the efficacy of Xixian Tongshuan Capsules/Pills in the treatment of acute ischemic stroke(AIS).Methods Literature about Xixian Tongshuan Preparation combined with conventional Western medicine for the treatment of AIS was retrieved from CNKI,SinoMed,VIP,Wanfang Data,PubMed,Medline,Embase,Cochrane Library and Web of Science from establishment of the databases to February 28,2023.Meta-analysis was conducted for the studies that could be quantitatively analyzed.The effective rate and response indicators were combined.Results A total of 7 articles were included for Meta-analysis.Results showed that there was statistical difference in the effective rate(RR=0.34,95%CI[0.23,0.51],P<0.01),NIHSS score(MD=-2.90,95%CI[-3.74,-2.06],P<0.01),BI score(MD=-10.08,95%CI[-13.47,-6.68],P<0.01),FIB(MD=-1.18,95%CI[-1.59,-0.77],P<0.01)of Xixian Tongshuan Preparation combined with conventional Western medicine for the treatment of AIS.There was no statistical difference in IL-6(MD=-15.4,95%CI[-33.3,2.49],P=0.09).There was no statistical difference in the effects of different dosage forms and treatment courses on the effective rate and NIHSS score.Conclusion The combination of Xixian Tongshuan Capsules/Pills could better improve the NIHSS and BI scores of patients with AIS,recovery the neurological function,and reduce the risk of blood hypercoagulability by reducing FIB content,with good safety.

Objective:To investigate the efficacy of double S-shaped elastic stable intramedullary nailing in the treatment of paediatric fractures of the distal tibia diaphyseal metaphyseal junction.Methods:From January 2018 to January 2022, a total of 25 children with fracture of the distal tibia diaphyseal metaphyseal junction were treated at Department of Pediatric Orthopedics, The Second Affiliated Hospital of Inner Mongolia Medical University. All of them were treated with closed reduction and double S-shaped elastic stable intramedullary nailing. There were 16 males and 9 females with an average age of (10.4±3.3) years, and 14 left sides and 11 right sides. The operation time, imaging results and complications were recorded after operation. At the last follow-up, the American Orthopaedic Foot & Ankle Society (AOFAS) scoring was used to evaluate the efficacy.Results:Closed reduction succeeded in all patients. The operation time was (55.6±23.7) min. Follow-up lasted (20.5±4.7) months for this cohort. Bony union was achieved in all patients after (11.5±2.7) weeks. No postoperative complications occurred in the patients, like infection, loss of reduction, disparity in length of lower limbs, delayed union or non-union. The AOFAS scoring at the last follow-up yielded 23 excellent and 2 good cases, and an excellent and good rate of 100% (25/25).Conclusion:In the treatment of paediatric fractures of the distal tibia diaphyseal metaphyseal junction, double S-shaped elastic stable intramedullary nailing is a safe, effective and feasible option.

Objective:To investigate the safety and efficacy of balloon pulmonary angioplasty (BPA) for residual pulmonary hypertension (PH) of chronic thromboembolic pulmonary hypertension(CTEPH) after pulmonary endarterectomy (PEA).Methods:Patients diagnosed as PH after PEA in China-Japan Friendship Hospital from Oct 2016 to Jun 2022 were included. The indication for BPA was decided on the basis of a consensus of the multi-disciplinary team for all patients with CTEPH. Before treatment, the patient′s exercise tolerance and pulmonary artery flow parameters were evaluated. A comparative analysis of various parameters before BPA treatment and at the last BPA was conducted. 6-min walk distance (6MWD) was analyzed using the paired Wilcoxon test; N-terminal pro-brain natriuretic peptide (NT-proBNP), mixed venous oxygen saturation, mean pulmonary arterial pressure (mPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were compared using the paired-samples t-test. WHO functional class was compared using McNemar′s test. Results:Twenty patients with a total of 130 vessels underwent 46 sessions of BPA treatment. The postoperative 6-minute walk distance (6MWD) [447 (415, 485) m] showed a significant improvement compared to the preoperative baseline [389 (335, 470) m] ( Z=6.52, P<0.05), Postoperative mixed venous oxygen saturation (72.0%±1.9%) showed a significant improvement compared to the preoperative levels (64.0%±2.7%) ( t=2.14, P<0.05).Postoperatively, plasma NT-proBNP [(351.9±129.9) pg/ml], mPAP [(24.2±1.9) mmHg], and PVR [(3.0±1.4) WU] significantly decreased compared to preoperative levels [(982.5±426.2) pg/ml, (33±2.1) mmHg, (8.0±1.6) WU)] ( t=3.38, 1.22, 2.10, P<0.05 for all). Postoperatively, there was a significant improvement in WHO functional class (Ⅰ，Ⅱ，Ⅲ，Ⅳ: 14, 4, 2, 0 cases) compared to preoperative status (Ⅰ，Ⅱ，Ⅲ，Ⅳ: 0, 13, 5, 2 cases) ( χ2=20.17, P<0.05). Four cases of pulmonary artery dissection and one episode of hemoptysis occurred postoperatively, with no other complications reported. Conclusions:BPA can significantly improve exercise tolerance and hemodynamic parameters for residual PH after PEA. BPA is a relatively safe and effective treatment for residual PH after PEA.

Cerebrospinal fluid morphology examination is an important method of diagnosing central nervous system diseases, but manual microscopy has shortcomings such as low efficiency, long staff training period, and poor homogeneity of test results. In recent years, the application of artificial intelligence in the medical field has developed rapidly, providing new technical means for cerebrospinal fluid morphology examination. In the future, AI-assisted morphological examination of cerebrospinal fluid will not only realize digitalization and networking, but also improve the level and efficiency of intelligent diagnosis of cerebrospinal fluid morphology, which has a broad application prospect in the intelligent assisted diagnosis of cerebrospinal fluid.

Objective:To analyze the quality of surgical specimens of rectal cancer in the Chinese transanal total mesorectal excision (taTME) registry collaborative (CTRC) database.Methods:The retrospective and descriptive study was conducted. Based on the concept of real-world research, the clinicopathological data of 1 761 patients with rectal cancer in the CTRC database who underwent taTME in 40 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15, 2017 to December 31, 2022 were collected. There were 1 212 males and 549 females, aged 62(range, 53-68)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations. Measurement data with skewed distri-bution were represented as M(range). Count data were described as absolute numbers. Results:(1) Preoperative examinations. Of the 1 761 patients, 1 324 patients underwent preoperative pelvic magnetic resonance imaging examination, and the results showed that 4 cases as clinical T0 stage, 30 cases as clinical T1 stage, 250 cases as clinical T2 stage, 828 cases as clinical T3 stage, 141 cases as clinical T4 stage, 11 cases as clinical Tx stage, 60 cases missing clinical T staging data, 490 cases as clinical N0 stage, 373 cases as clinical N1 stage, 311 cases as clinical N2 stage, 86 cases as clinical Nx stage, 64 cases missing clinical N staging data, 156 cases with mesorectal fascia invasion, 223 cases with extraintestinal blood vessels invasion. The distance from lower margin of tumor to anal margin of 1 324 patients was 50(range, 40-60)mm. (2) Neoadjuvant therapy. Of the 1 761 patients, 873 patients underwent neoadjuvant therapy, including 17 cases receiving radiotherapy alone, 155 cases receiving chemotherapy alone, 43 cases receiving short-course simultaneous chemoradiotherapy, 26 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 1 case receiving contact radiotherapy, 277 cases receiving long-course simultaneous chemoradiotherapy, 9 cases receiving other treatments, and 345 cases missing neoadjuvant therapy data. (3) Postoperative examinations. Of the 1 761 patients, 1 584 cases achieved R 0 resection, 23 cases achieved R 1 resection, 1 case achieved R 2 resection, and there were 153 cases missing surgical margin data. The tumor diameter, number of lymph nodes harvest and positive rate of intravascular tumor thrombus were 30(range, 20-45)cm, 13(range, 10-17) and 20.794%(330/1 587) in 1 761 patients. There were 1 647 patients with circumferential margin records, which showed positive in 51 cases, and the minimum distance from deep part of tumor to circumferential margin was 5(rang, 3-13)mm in 1 647 patients. There were 547 cases with distal margin records, which showed positive in 4 cases, and the distance from lower margin of tumor to distal margin was 20(10-25)mm in 547 cases. There were 1 698 patients with specimen integrity records, which showed intact specimen in 1 436 cases, fair specimen in 233 cases, poor specimen in 8 cases, unevaluated specimen in 21 cases, and there were 20 cases with rectal tube perforation. Of the 1 761 patients, cases as pathological T0 stage, Tis stage, T1 stage, T2 stage, T3 stage, T4 stage was 103, 23, 145, 515, 712, 179, respectively, and there were 4 cases of pathology that could not be evaluated and 80 cases missing pathological T staging data. Of the 1 761 patients, cases as pathological N0 stage, N1a stage, N1b stage, N1c stage, N2a stage, N2b stage was 1 117, 189, 133, 66, 109, 68, respectively, and there were 79 cases missing pathological N staging data. Of the 1 761 patients, there were 79 cases with distant metastasis, 1 591 cases without distant metastasis, and 91 cases without data of tumor metastasis. Of the 873 patients undergoing neoadjuvant therapy, there were 405 patients with tumor regression grade records including 105 cases as grade 1, 142 cases as grade 2, 91 cases as grade 3, 43 cases as grade 4, 24 cases as grade 5. Conclusions:In China, the quality of surgical specimens of taTME for rectal cancer is good with low positive rate of resection margin. It is recommended that using a formatted postoperative pathological report for good quality control of pathological report of surgical specimen.

BACKGROUND: Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity. METHODS: First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells. RESULTS: A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC. CONCLUSIONS A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.
Humans ; Mice ; Animals ; Psilocybin/metabolism* ; Fear ; Extinction, Psychological ; Brain-Derived Neurotrophic Factor/metabolism* ; Bromodeoxyuridine/pharmacology* ; Hippocampus/metabolism* ; Neuronal Plasticity ; TOR Serine-Threonine Kinases/metabolism*