Objective To explore the expression levels of CD33⁺ myeloid-derived suppressor cell (MDSC)-mediated T lymphocyte function and related inflammatory factors secreted by T lymphocyte subsets in patients with cervical cancer, and to analyze their correlation with the treatment efficacy of ¹²⁵I particle implantation combined with arterial chemoembolization, as well as predictive value for treatment outcomes and interaction effects. Methods From January 1st, 2021 to January 1st, 2024, our hospital admitted 152 patients with advanced cervical cancer, who were confirmed by pathological examination. All patients received uterine artery chemoembolization combined with ¹²⁵I particle implantation. The predictive value of CD33⁺MDSC levels for clinical treatment response in cervical cancer was assessed using receiver operating characteristic (ROC) curve analysis. Multivariate logistic regression analysis was performed to evaluate both multiplicative and additive interactions between CD33⁺MDSC and T lymphocytes in predicting clinical treatment failure of cervical cancer. Kaplan Meier method was used to analyze the survival differences between cervical cancer patients with high and low CD33⁺MDSC expression levels. Results Compared with the effective group, patients in the ineffective group had decreased expression levels of CD3⁺ T lymphocyte, CD4⁺ T lymphocyte, interleukin 2 (IL-2) and interferon γ (IFN-γ), while showing increased expression levels of CD33⁺MDSC, CD8⁺ T lymphocyte, IL-4 and IL-6, along with increased tumor necrosis factor α (TNF-α) levels, larger maximum tumor diameters, and a higher incidence of lymph node metastasis. The expression levels of CD33⁺MDSCs demonstrated good predictive performance for treatment efficacy in cervical cancer patients. The high CD33⁺MDSC expression group had a significantly shorter overall survival (OS) than the low CD33⁺MDSC expression group (6.0±1.0 months vs. 12.0±1.2 months; t=33.280). The interaction analysis revealed that CD33⁺MDSCs and CD8⁺ T lymphocytes were highly expressed, while CD3⁺ and CD4⁺ T lymphocytes were lowly expressed, which was associated with an increased risk of clinical treatment failure in cervical cancer patients. Conclusion CD33⁺MDSCs can inhibit CD3⁺ and CD4⁺ T lymphocytes. It can upregulate the expression of CD8⁺ T lymphocytes, form an immunosuppressive microenvironment, and reduce the treatment response rate of ¹²⁵I particle implantation combined with arterial chemoembolization. CD33⁺MDSCs may serve as an independent biomarker for predicting the therapeutic efficacy and poor prognosis.
Humans ; Female ; Uterine Cervical Neoplasms/immunology* ; Middle Aged ; Chemoembolization, Therapeutic/methods* ; Sialic Acid Binding Ig-like Lectin 3/immunology* ; Adult ; T-Lymphocytes/immunology* ; Aged ; Treatment Outcome

Objective: To investigate the prevalence and influencing factors of latent tuberculosis infection (LTBI) among students close contacts diagnosed with pulmonary tuberculosis in Baoshan District, Shanghai, so as to provide the basis for the prevention and control of pulmonary tuberculosis among students. Methods: Pulmonary tuberculosis cases identified among students or teaching staff were selected as index cases through the Surveillance System of Chinese Disease Prevention and Control Information System, school reports, notification of Centers for Disease Control and Prevention from April 2021 to November 2023, and student close contacts in their schools were selected as research subjects. Demographic information, lifestyle and Mycobacterium tuberculosis test results were collected through questionnaires surveys and pulmonary tuberculosis screening. LTBI was defined as a positive Mycobacterium tuberculosis test result with the exclusion of active pulmonary tuberculosis. The influencing factors for LTBI among student close contacts were identified using a multivariable logistic regression model. Results: A total of 1 212 student close contacts were included, with 651 males and 561 females, resulting in a gender ratio of 1.16︰1. The mean age was (18.48±4.33) years. Among them, 32 cases were detected with LTBI, yielding a detection rate of 2.64%. Higher LTBI detection rates were observed among students who shared the same dormitory with pulmonary tuberculosis cases (9.26%), attended private schools (5.54%), lived on campus (3.54%), and obtained meals through take-out services (6.52%). Multivariable logistic regression analysis showed that sharing the same dormitory with pulmonary tuberculosis cases (OR=3.604, 95%CI: 1.256-10.338), attending a private school (OR=2.327, 95%CI: 1.083-5.003), and three meals a day through canteens (OR=9.561, 95%CI: 2.029-45.057) or through take-out services (OR=19.222, 95%CI: 3.528-104.732) were associated with a higher risk of LTBI. Conclusion The close contacts of students with pulmonary tuberculosis in Baoshan District are at risk of LTBI, which is mainly affected by the degree of contact with tuberculosis cases, the strength of school epidemic prevention and control, and students' eating habits.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population. Methods:This is a multi-center,randomized,double-blind,placebo-controlled phase Ⅲ clinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed. Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(all P<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05). Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.

Objective:Exploring the effect of recovery-oriented family psychoeducation on the level of social support and family resilience of patients with schizophrenia in remission stage, providing theoretical basis for clinical application.Methods:Using a randomized controlled trial method and convenience sampling method, 60 patients with schizophrenia in remission who visited the outpatient department of the Affiliated Mental Health Center of Shanghai Jiao Tong University School of Medicine from April 2020 to March 2022 were selected as the study subjects, and they were divided into experimental group and control group, with 30 patients in each group according to their residence places. The control group was given routine health education; the experimental group was given the rehabilitation oriented family psychoeducation, before intervention and 3 months after intervention, Social Support Rating Scale and Family Resilience Questionnaire were used to evaluate the intervention effect.Results:A total of 60 patients were included in the control group, including 13 males and 17 females, aged (27.0 ± 6.5)years.In the experimental group, there were 14 males and 16 females, aged (28.0 ± 5.6) years. After intervention, the scores of subjective support, objective support and social support utilization in Social Support Rating Scale of the experimental group were 14.33 ± 3.36, 8.43 ± 1.63 and 9.60 ± 2.49, respectively, the control group were 16.20 ± 3.83, 10.00 ± 2.59 and 8.33 ± 2.28, respectively, and the differences were statistically significant ( t=2.00, 2.80, -2.05, all P<0.05). After intervention, the total score of Family Resilience Questionnaire and the scores of perseverance, support and harmony were 78.77 ± 9.61, 24.90 ± 3.07, 15.10 ± 2.23 and 23.63 ± 3.04, respectively. Higher than the control group 72.67 ± 15.96, 23.43 ± 4.92, 14.03 ± 3.60, 21.13 ± 5.13, the differences were statistically significant ( t values were -2.29--1.37, all P<0.05). Conclusions:Recovery-oriented family psychoeducation can improve the level of social support and family resilience of schizophrenia patients in remission.

Objective:To explore the safety and effectiveness of laparoscopic local pancreatectomy in the treatment of cystic neoplasms of pancreatic head.Methods:Retrospective analysis was conducted of data on patients with pancreatic head cystic neoplasms who received laparoscopic surgery at the Department of Hepatobiliary Surgery, the Second Hospital of Hebei Medical University from February 2017 to October 2022. A total of 83 patients were enrolled, including 30 males and 53 females, aged (43.7±16.7) years old. All patients were divided into an observation group ( n=55) and a control group ( n=28) based on different surgical procedures. The observation group underwent laparoscopic local pancreatectomy (laparoscopic duodenum-preserving pancreatic head resection or laparoscopic enucleation), while the control group underwent laparoscopic pancreaticoduodenectomy (LPD). The age, gender, body mass index, postoperative hospital stay, proportion of discharged patients with drainage tubes, surgical time, intraoperative blood loss, intraoperative blood transfusion rate, and fistula were compared between two groups. Results:All patients successfully completed the surgery, and there were no cases of conversion to laparotomy or perioperative deaths. There was no statistically significant difference in age, male proportion, body mass index, postoperative hospital stay, and discharge rate with drainage tube between the two groups of patients (all P>0.05). The observation group had a surgical time of (194.4±114.0) min, intraoperative bleeding of 50 (50, 200) ml, and intraoperative blood transfusion rate of 5.5%(3/55), all of which were better than that of the control group, (380.0±71.6) min, 200 (100, 400) ml, and 32.1%(9/28), with statistical significance (all P<0.05). Among them, the B/C fistula rates in the laparoscopic local pancreatectomy group and LPD group were 12.7%(7/55) and 10.7%(3/28) ( P=0.790), respectively. Conclusion:Compared with traditional LPD, laparoscopic local pancreatectomy can shorten surgical time, reduce intraoperative bleeding, and lower intraoperative blood transfusion rate. And there is no significant disadvantage in the B or C grade fistula.

The blood-brain barrier (BBB) impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases (AAND). Meanwhile, circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity of neurological diseases in the accelerated aging population. Importantly, circadian rhythms disruption and gut microbiota dysbiosis are also known to induce the generation of toxic metabolites and pro-inflammatory cytokines, resulting in disruption of BBB integrity. Collectively, this provides a new perspective for exploring the relationship among circadian rhythms, gut microbes, and the BBB in aging-accompanied neurological diseases. In this review, we focus on recent advances in the interplay between circadian rhythm disturbances and gut microbiota dysbiosis, and their potential roles in the BBB disruption that occurs in AAND. Based on existing literature, we discuss and propose potential mechanisms underlying BBB damage induced by dysregulated circadian rhythms and gut microbiota, which would serve as the basis for developing potential interventions to protect the BBB in the aging population through targeting the BBB by exploiting its links with gut microbiota and circadian rhythms for treating AAND.

AIM: Diabetes mellitus affects the pharmacokinetics of cytochrome P450 3A4 / 5 (CYP3A4/5) substrates. We evaluated the relationship between haemoglobin A1c (HbA1c) levels and the pharmacokinetics of controlled-release tacrolimus. METHODS: This retrospective observational cohort study included kidney transplant recipients (>18 years) receiving controlled-release tacrolimus orally. CYP3A5 genotypes were categorized as expressers (*1/*1 or *1/*3) and non-expressers (*3/*3). Multiple linear regression analysis determined the predictors for trough concentration / dose-normalized by body weight (C/D) ratio of tacrolimus at 7 days, 6 months and 12 months after administration. Correlations between the C/D ratio and HbA1c levels at baseline, 6 and 12 months after tacrolimus initiation were evaluated with Bonferroni correction. RESULTS: Out of 42 patients (CYP3A5 expressers, n=56, and non-expressers, n= 83), the multiple linear regression analysis showed that the C/D ratio on Day 7 was marginally higher in CYP3A5 non-expressers than in CYP3A5 expressers. Factors affecting the elevation of tacrolimus C/ D ratio after 6 and 12 months of treatment were male sex and CYP3A5 non-expressers and increased HbA1c levels and CYP3A5 non-expressers, respectively. The C/D ratio and HbA1c levels after 12 months was positively correlated in CYP3A5 non-expressers (y=54.6x+194.6, R=0.63, P=0.004, Bonferroni correction). Furthermore, intra-individual changes in the C/D ratio and HbA1c levels from 6 to 12 months were nearly correlated (y=54.5x + 20.2, R=0.41, P=0.036, Bonferroni correction). CONCLUSION: HbA1c and CYP3A5 genotypes might be considered to understand the inter- and intra-individual variability in blood tacrolimus concentrations after 6 months post-kidney transplantation.

Objective:To investigate the application value of mixed reality technology in surgical conversation of laparoscopy radical resection of gastric cancer.Methods:The prospective randomized controlled study was conducted. There were 80 family members of patients with gastric cancer who were admitted to Nanfang Hospital of Southern Medical University from June 2021 to December 2022 being selected as subjects. All patients underwent laparoscopic radical resection of gastric cancer. Based on random number table, all subjects were allocated into the control group and the experiment group. Subjects in the control group performed routine surgical conversation and subjects in the experiment group performed surgical conversation based on mixed reality technology. Observation indicators: (1) baseline data of the subjects; (2) anxiety assessment of the subjects. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for inter-group comparison. Repeated measurement data were analyzed using the repeated ANOVA. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Wilcoxon rank sum test. Results:(1) Baseline data of the subjects. A total of 80 subjects were selected for eligibility, including 40 subjects in the control group and 40 subjects in the experi-ment group. There were 44 males and 36 females, aged (40±9)years. The gender (male, female), age, education background (primary school education, middle school education, high school education, junior college education, undergraduate education, postgraduate education) were 23, 17, (39±9)years, 1, 3, 9, 16, 9, 2 in subjects of the control group, versus 25, 15, (42±10)years, 0, 8, 6, 11, 14, 1 in subjects of the experiment group, showing no significant difference in the above indicators between the two groups ( χ2=0.20, t=?1.64, Z=?0.10, P>0.05). (2) Anxiety assessment of the subjects. The scores of self-rating Anxiety Scale (SAS) and Hospital Anxiety Scale (HADS) before surgical conversation, after surgical conversation, after surgery were 41±10 and 26±5, 49±11 and 32±3, 40±13 and 15±8 in subjects of the control group, versus 44±9 and 23±3, 66±16 and 28±6, 34±14 and 8±3 in subjects of the experiment group, showing significant differences in the above indicators between the two groups ( FSAS组间=8.83, FSAS时间=40.41, FSAS交互=12.21, FHADS组间=32.42, FHADS时间=321.28, FHADS交互=6.15, P<0.05). Conclusion:Compared with traditional surgical conversation, mixed reality technology based surgical conversation can relieve the postoperative conxiety of subjects.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*