Autophagy is a fundamental biological metabolic process involved in immune defense, material metabolism, and homeostasis and closely linked to immune regulation. Systemic lupus erythematosus (SLE) is a widespread connective tissue disorder primarily resulting from immune system imbalance. Due to the immune system's failure to recognize its own substances, it generates autoantibodies that can affect various tissues and organs, leading to diverse clinical manifestations. The pathogenesis and treatment of SLE are currently under extensive investigation. In normal metabolic processes, autophagy engages in both innate and adaptive immunity, regulates the immune response, and is crucial for maintaining normal immune function and the body's internal homeostasis. Research has indicated that SLE patients exhibit immune dysfunction and altered autophagy levels. Modulating autophagy expression can influence immune system functionality and alleviate SLE symptoms. Additionally, autophagy aids in the innate immune response and adaptive immunity by clearing metabolites and regulating the life cycle of immune cells. Studies suggest that drugs targeting autophagy can positively influence the progression of SLE. This article reviews advancements in research regarding the impact of autophagy on the pathogenesis of SLE through the regulation of immune system functions.
Lupus Erythematosus, Systemic/pathology* ; Autophagy/immunology* ; Humans ; Animals ; Immunity, Innate ; Adaptive Immunity ; Disease Progression ; Immune System/immunology*

OBJECTIVES: To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism. METHODS: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay. RESULTS: MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera. CONCLUSIONS YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals ; MicroRNAs/genetics* ; Podocytes/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Autophagy/drug effects* ; Rats, Wistar ; Protein Kinases/metabolism* ; Rats ; Forkhead Box Protein O1 ; Mice ; Mitochondria/drug effects* ; Ubiquitin-Protein Ligases/metabolism* ; Glucose ; Diabetic Nephropathies ; Male ; Membrane Proteins/metabolism* ; Intracellular Signaling Peptides and Proteins

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Objective:To determine the risk factors for permanent nerve damage (PND) after aortic arch surgery in patients with acute type A aortic dissection (AAAD).Methods:This was a retrospective case-control study. The medical records from patients of both sexes with AAAD, aged > 18 yr, of American Society of Anesthesiologists Physical Status classification IV, who underwent aortic arch surgery in the Second Hospital of Hebei Medical University from December 2018 to December 2023, were collected. The patients were divided into non-PND group and PND group according to whether PND occurred after operation. The preoperative data of patients were collected, including age, gender, body mass index; comorbidities (hypertension, coronary heart disease, diabetes mellitus), history of smoking, history of stroke, and history of cardiovascular surgeries; syncope at onset, preoperative low SpO 2, preoperative low systolic blood pressure, and preoperative low diastolic blood pressure. The intraoperative data included surgical procedure (total aortic arch replacement or half aortic arch replacement), selective antegrade cerebral perfusion during operation, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, post-parallel time, moderate hypothermia circulatory arrest time, nasopharyngeal temperature and rectal temperature during circulatory arrest, and BIS value during circulatory arrest; blood pressure during cardiopulmonary bypass and after restoration of heart beat; the incidence of dysfunction after recovery of heart beat and difficulty in hemostasis after termination of CPB. The aforementioned indicators were analyzed for difference, and the indicators with P<0.05 were included in the multivariate logistic regression analysis. Results:A total of 292 patients were ultimately included, among which 73 developed postoperative PND, resulting in an incidence of 25.0%. The results of multivariate logistic regression analysis showed that age ≥62 yr ( OR=3.783, 95% confidence interval [ CI] 1.513-10.346, P=0.006), preoperative hypertension ( OR=2.230, 95% CI 1.118-4.715, P=0.028), syncope at onset ( OR=3.001, 95% CI 1.343-6.710, P=0.007), BIS value > 14 during circulatory arrest ( OR=2.439, 95% CI 1.249-4.755, P=0.009) and difficult hemostasis after termination of CPB ( OR=3.465, 95% CI 1.758-6.882, P<0.001) were risk factors for PND after surgery. Conclusions:Age ≥ 62 yr, history of hypertension, syncope at onset, BIS value greater than 14 during circulatory arrest and difficulty in hemostasis after termination of CPB are risk factors for PND after aortic arch surgery in patients with AAAD.

OBJECTIVE To construct a comprehensive evaluation index system for anti-lung cancer drugs， and to provide a basis for drug selection and rational clinical use. METHODS Based on the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs （2021 edition for trial use）， a preliminary evaluation index system framework and an index preselection pool were initially formulated through literature analysis. The evaluation indices were then selected and modified by using the Delphi method. The weights of each index were determined through expert scoring and relevant calculations， thereby establishing a comprehensive evaluation index system for anti-lung cancer drugs. Referred to Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions， scoring detailed rules for clinical comprehensive evaluation indexes of anti-lung cancer drugs were formulated. The constructed comprehensive evaluation index system and scoring detailed rules were applied to conduct empirical evaluation of the anti-lung cancer drug pembrolizumab. RESULTS The constructed comprehensive evaluation index system for anti-lung cancer drugs included 6 primary indicators and 15 secondary indicators. The weights of the primary indicators were as follows： safety （18）， efficacy （38）， economy （15）， innovation （9）， suitability （10）， and accessibility （10）. The scoring detailed rules for the comprehensive evaluation index system for anti-lung cancer drugs had been preliminarily established. The results of empirical evaluation showed that the comprehensive evaluation score （61 points） of pembrolizumab combined with chemotherapy regimen was higher than that of the monotherapy chemotherapy regimen （56 points）. The former demonstrated superior efficacy， innovation and suitability compared to the latter， while the latter exhibited better safety and economy. CONCLUSIONS The constructed comprehensive evaluation index system for anti-lung cancer drugs has the potential for generalizability and practical application， providing a reference basis for rational clinical drug use.

Objective:To investigate the clinical characteristics and prognosis of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies.Methods:A total of 216 non-acquired immunodeficiency syndrome (AIDS) related cryptococcal meningitis cases with positive cultures of Cryptococcus, hospitalized at Huashan Hospital, Fudan University during January 2014 and December 2021, were retrospectively included. The serum anti-GM-CSF autoantibodies were detected by enzyme linked immunosorbent assay, and the clinical characteristics and prognosis were compared between patients with and without anti-GM-CSF autoantibodies. Statistical comparisons were mainly performed using the chi-square test or Fisher′s exact test. Cox proportional-hazards model was used to analyze the risk factors associated with prognosis. Results:Among 216 enrolled patients, 23 patients were positive of anti-GM-CSF autoantibodies, with a positive rate of 10.6%. Among 23 patients, seven cases were infected with Cryptococcus gattii, and 16 cases were infected with Cryptococcus neoformans. In the group with positive anti-GM-CSF autoantibodies, 30.4%(7/23) of the patients were infected with Cryptococcus gattii, which was higher than that of 1.6%(3/193) in the group with negative anti-GM-CSF autoantibodies, and the difference was statistically significant ( χ2=38.82, P<0.001). In the group with positive anti-GM-CSF autoantibodies, 30.0% (6/20) had mass lesions with a diameter greater than three centimeters in the lungs, and the one-year all-cause mortality rate was 50.0% (10/20), which were both higher than those of 3.4%(5/145) and 16.1% (29/180) in the negative group, respectively. The differences were both statistically significant (both Fisher′s exact test, P<0.01). Age≥60 years (hazard ratio ( HR)=4.146, P=0.002), predisposing factors ( HR=3.160, P=0.021), epilepsy ( HR=6.129, P=0.002), positive anti-GM-CSF autoantibodies ( HR=2.675, P=0.034), white blood cell count of cerebrospinal fluid (CSF)<100 ×10 6/L ( HR=2.736, P=0.039), the titers of cryptococcal capsular polysaccharide antigen of CSF≥1∶1 280 ( HR=4.361, P=0.009) were independent risk factors for one-year all-cause mortality in patients with cryptococcal meningitis. Conclusions:In non-AIDS related cryptococcal meningitis patients, the positive rate of serum anti-GM-CSF autoantibodies is as high as 10.6%. Patients with anti-GM-CSF autoantibodies could be infected with both Cryptococcus neoformans and Cryptococcus gattii, and they have higher proportion of lung mass lesions than patients with negative anti-GM-CSF autoantibodies. The one-year survival rate decreases significantly in patients with anti-GM-CSF autoantibodies, which is an independent risk factor for the prognosis of cryptococcal meningitis.

Objective:To develop a constant temperature disinfection device and evaluate its clinical effect in perineal disinfection after delivery.Methods:A total of 300 cases of puerpera who met the inclusion and exclusion criteria were selected from Heping Hospital Affiliated to Changzhi Medical College from November to December 2020. The study was designed as a randomized control study. Subjects were randomly divided by random digit table into the control group and the experimental group of 150 cases respectively. The former used conventional methods for perineal disinfection after delivery. The latter performed perineal disinfection assisted by a thermostatic disinfection device. The temperature comfort of perineal disinfection and the perineal wound healing of perineal tear or lateral incision were compared between two groups.Results:The score of temperature comfort feeling of puerpera in the control group and the experimental group was 3 (1.5) and 5 (0), respectively. The maternal temperature comfort feeling score in the experimental group was higher, and the difference between the two groups was statistically significant ( Z=-13.78, P<0.05). There was no grade C healing of perineal wounds in the two groups. The composition ratios of grade A and grade B healing of perineal wounds in the control group were 89.61% (69/77) and 10.39% (8/77), and those in the experimental group were 93.75% (90/96) and 6.25% (6/96). The healing of perineal wound in the latter group was better, but the difference between the two groups was not statistically significant ( Z=0.99, P>0.05). Conclusions:The constant temperature disinfection device meets the clinical nursing needs, enhances the comfort experience of puerpera, and has certain effect on promoting the healing of perineal wound after delivery.

The parahippocampal gyrus-orbitofrontal cortex (PHG-OFC) circuit in humans is homologous to the postrhinal cortex (POR)-ventral lateral orbitofrontal cortex (vlOFC) circuit in rodents. Both are associated with visuospatial malfunctions in Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. In this study, we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice, and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging (MRI) in patients on the AD spectrum. We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice. Moreover, MRI measurements of the PHG-OFC circuit had an accuracy of 77.33% for the classification of amnestic mild cognitive impairment converters versus non-converters. Thus, the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD, thereby providing a potential predictor for AD progression and a promising interventional approach for AD.

Objective:To investigate the prevalence and genotype distribution of high-risk human papillomavirus (HR-HPV) and the correlation between cervical lesions and analyze the risk factors for HR-HPV infection.Methods:In June 2018, a population-based study for cervical cancer screening in Tuoli county of Xinjiang Uygur Autonomous Region was conducted. A total of 2 000 Kazak women aged 25-64 years were included in the study. Three cervical exfoliated cells samples were collected from them for careHPV, PCR HPV, p16 INK4a, and liquid-based cytology (LBC) tests. Women with any positive test were referred for colposcopy with biopsies taken at abnormal sites. Histo-pathological diagnoses were used as the gold standard. Results:The overall prevalence of HPV was 14.55%, among which the infection rate of HR-HPV was 12.90%, which was even higher in the 50-54 years age group. The most prevalent genotypes of HR-HPV were HPV16 (2.80%), HPV51(2.35%), HPV52 (1.70%), HPV56 (1.50%), and HPV39 (1.20%). The most common HPV infection was a single infection (71.48%). In the age group of 50-54 years, the multiple infection rates were higher, with the majority of double infection (69.88%), and HPV42 and 56 were the most common co-infection types. HPV16 (31.82%), HPV51 (27.27%) and HPV18 (13.64%) were higher in cervical intraepithelial neplasia grade 1, HPV16 (57.14%) was higher in cervical intraepithelial neplasia grade 2, and HPV16 (55.56%) and HPV18 (33.33%) were higher in cervical intraepithelial neplasia grade 3 or worse. Results from the multivariate logistic regression analysis showed that higher education, menopause, and syphilis infection increased the HPV infection.Conclusions:The most common prevalence genotypes of HR-HPV among Kazak women were HPV16, HPV51, and HPV52. The infection rate of HR-HPV among Kazak women was correlated with education level, menopausal status, and syphilis infection. Measures should be taken targeting high-risk factors. This result suggests that STD patients and women aged 50 and above should be encouraged for screening.