OBJECTIVES: The integrated endoplasmic reticulum stress inhibitor (ISRIB) is a selective inhibitor of the protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway within endoplasmic reticulum stress (ERS) and can improve spatial and working memory in aged mice. Although ERS and oxidative stress are tightly interconnected, it remains unclear whether ISRIB alleviates cognitive impairment by restoring the balance between ERS and oxidative stress. This study aims to investigate the effects and mechanisms of ISRIB on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: Eight-week-old male ICR mice were randomly divided into 3 groups: Normal saline (NS) group, LPS group, and ISRIB+LPS group. NS and LPS groups received daily intraperitoneal injections of normal saline for 7 days; on day 7, LPS group mice received intraperitoneal LPS (0.83 mg/kg) to establish a cognitive impairment model. ISRIB+LPS group received ISRIB (0.25 mg/kg) intraperitoneally for 7 days, with LPS injected 30 minutes after ISRIB on day 7. Cognitive ability was evaluated by the novel place recognition test (NPRT). Real-time fluorogenic quantitative PCR (RT-qPCR) was used to detect changes in nitric oxide synthase (NOS), superoxide dismutase-1 (SOD-1), and catalase (CAT) gene expression in the hippocampus and prefrontal cortex. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG), were measured in hippocampal and prefrontal cortex tissues. RESULTS: Compared with the NS group, mice in LPS group showed a significant reduction in novel place recognition ratio, upregulation of hippocampal NOS-1 and NOS-2 mRNA, downregulation of SOD-1 and CAT mRNA, increased MDA and GSSG, decreased GSH, and reduced GSH/GSSG ratio (all P<0.05). Compared with the LPS group, mice in ISRIB+LPS group exhibited significantly improved novel place recognition, downregulated NOS-1 and NOS-2 mRNA, upregulated SOD-1 and CAT mRNA, decreased MDA and GSSG, increased GSH, and an elevated GSH/GSSG ratio in the hippocampus (all P<0.05). No significant changes were observed in the prefrontal cortex. CONCLUSIONS ISRIB improves LPS-induced cognitive impairment in mice by restoring the oxidative/antioxidant balance in the hippocampus.
Animals ; Lipopolysaccharides ; Male ; Mice, Inbred ICR ; Cognitive Dysfunction/drug therapy* ; Mice ; Oxidative Stress/drug effects* ; Endoplasmic Reticulum Stress/drug effects* ; Hippocampus/drug effects* ; Nitric Oxide Synthase Type II/genetics* ; Guanidines/pharmacology* ; eIF-2 Kinase/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Superoxide Dismutase/metabolism*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4⁺/CD8a⁺ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Objective To develop a whole course management information system for breast cancer and verify its effect in disease management of breast cancer patients.Methods An integrated service plan and system construction of"screening-diagnosis-treatment-rehabilitation"was developed,and then an information system was developed.The method of historical control was used to conveniently sample 260 cases of breast cancer patients diagnosed in a tertiary A hospital.130 cases diagnosed from May 1 to December 31,2022 were taken as a test group,and 130 cases diagnosed from May 1 to December 31,2021 were taken as a control group.The test group was managed by the whole course management information system,and the control group was managed by conventional disease management.The relevant indicators of the screening and diagnosis period of patients,the completion rate of treatment,the incidence of treatment related side effects and the cancer care satisfaction of the 2 groups were compared.Results There was a statistically significant difference in puncture waiting time,admission waiting time,and screening admission time between the 2 groups(P＜0.05),while there was no statistically significant difference in pathological waiting time(P＞0.05).The treatment completion rate of the test group was higher(P＜0.05).The incidence of lymphedema,chest obstruction and abnormal sensation of upper limbs,subcutaneous hydrops within 6 months after operation and bone marrow suppression,liver function damage,radiation dermatitis and radiation pneumonia in the test group were lower than those in the control group(P＜0.05).The cancer care satisfaction of the test group after surgery and 6 months after surgery were higher than those of the control group(P＜0.05).Conclusion The whole course management information system for breast cancer can optimize the diagnosis and treatment process,raise the diagnosis and treatment efficiency,ensure the treatment completion rate,reduce the treatment complications and improve the cancer care satisfaction.

Inflammatory injury of the intestine is often accompanied by symptoms such as damage to intestinal mucosa, increased intestinal permeability, and intestinal motility dysfunction. Inflammatory factors spread throughout the body via blood circulation, and can cause multi-organ failure. Pyroptosis is a newly discovered way of programmed cell death, which is mainly characterized by the formation of plasma membrane vesicles, cell swelling until the rupture of the cell membrane, and the release of cell contents, thereby activating a drastic inflammatory response and expanding the inflammatory response cascade. Pyroptosis is widely involved in the occurrence of diseases, and the underlying mechanisms for inflammation are still a hot spot of current research. The caspase-1 mediated canonical inflammasome pathway of pyroptosis and caspase-4/5/8/11-mediated non-canonical inflammasome pathway are closely related to the occurrence and development of intestinal inflammation. Therefore, investigation of the signaling pathways and molecular mechanisms of pyroptosis in intestinal injury in sepsis, inflammatory bowel diseases, infectious enteristic, and intestinal tumor is of great significance for the prevention and treatment of intestinal inflammatory injury.
Humans ; Pyroptosis ; Inflammasomes/metabolism* ; Apoptosis ; Caspase 1 ; Inflammation

Objective:To systematically evaluate the clinical efficacy of Wuling capsules in the treatment of insomnia.Methods:The randomized controlled trial (RCT) literature related to the treatment of insomnia with Wuling capsules was searched by computer through PubMed, EMbase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wanfang, and VIP databases. These RCT literature was searched by using "Wuling capsule and Insomnia" as keywords, and the search time frame was from the establishment of each database to January 2022. The literature was screened and relevant data were collected according to the designed nesting criteria (patients accepted conventional western medicines such as benzodiazepines or new non-benzodiazepines were used as control group, and patients accepted Wuling capsules alone or combined with conventional western medicines were used as study group; the outcome measures included total response rate, total scores of Pittsburgh Sleep Quality Index or Sleep Disorders Rating Scale), and Meta-analysis was performed on the extracted literature data using Revman 5.4 software.Results:A total of 17 pieces of RCT literature met the criteria were finally included, with a total of 1493 patients, including 749 patients into the study group and 744 patients into the control group. The overall efficiency of the study group was significantly higher than that of the control group (relative risk [ RR]=1.270, 95%CI: 1.200-1.340, P<0.05), and total scores of Pittsburgh Sleep Quality Index scale in study group were significantly lower than those in the control group (weighted mean difference [ WMD]=-2.070, 95%CI: -2.610--1.520, P<0.05), and the total scores of Sleep Disorder Rating Scale in study groups were significantly lower than those in the control group ( WMD=-4.180, 95%CI: -4.900--3.450, P<0.05). Conclusion:The efficacy of Wuling capsules alone or combined with conventional western medicines in treating insomnia is better than that of conventional western medicines, and can obviously improve the quality of sleep of patients.

Objective:To investigate the effect of different blood glucose and BMI levels on the outcome of closed biliary surgery in diabetic patients.Methods:Clinical data of 424 diabetes admitted to Shanxi Provincial People’s Hospital for closed biliary tract surgery from Jan. 2018 to Jun. 2019 were retrospectively analyzed. According to the fasting blood glucose and BMI levels, the subjects were divided into hyperglycemia and non-hyperglycemia groups and obesity and non-obesity subgroups. The differences of clinical data among different groups were compared and analyzed. Multiple regression analysis was used to analyze the factors of postoperative infection, length and cost of hospitalization.Results:①Compared with the non-hyperglycemia group, the hyperglycemia group had higher BMI, serum creatinine, blood urea nitrogen, blood glucose monitoring rate, glycated hemoglobin detection rate, postoperative infection rate, ICU occupancy rate, length and cost of hospitalization, and lower albumin level, all P<0.05.②The age, fasting blood glucose, serum creatinine, low density lipoprotein, length and cost of hospitalization in the hyperglycemic obese subgroup were all lower than those in the non-obese subgroup, all P<0.05; and the serum creatinine in the obese subgroup was higher than those in the non-obese subgroup ( P<0.05) . ③Logistic analysis revealed that hyperglycemia was an independent risk factor for postoperative infection. For every 1mmol/L increase in fasting blood glucose, the risk of postoperative infection increased by 1.158 times, and albumin was a protective factor for postoperative infection. ④Multiple linear regression analysis showed that hyperglycemia and hypoalbumin were the important factors affecting the length of hospital stay and the increase of hospital cost, all P<0.05. Conclusions:Hyperglycemia is an independent risk factor for postoperative infection and a risk factor for longer hospital stay and higher costs. Obesity is not associated with postoperative infection or longer hospital stay, except for increased serum. Patients with diabetes undergoing closed biliary system surgery need to improve the detection rate of glycated hemoglobin and blood glucose monitoring rate, manage blood glucose reasonably, and control body weight appropriately.

Objective:This article takes the practical experience of the construction of the cardiovascular disease clinical medicine research center in Nanjing First Hospital as an example to provide reference for institutions preparing to build a clinical research center.Methods:The center conducts top-level design based on clinical needs, and this study systematically elaborates the construction of the center from management mechanisms, research platforms, collaborative networks, team building and international cooperation.Results:The center has made remarkable progress in clinical research, scientific and technological innovation, transformation and promotion, standard formulation, and technology leading. On the basis of an international perspective, the level of regional diagnosis and treatment has been improved by optimizing the structure of subject talents, and focusing on the clinical needs of cardiovascular subspecialty.Conclusions:Taking the construction of the clinical medicine center as an opportunity, integrating superior resources, improving the level of disease diagnosis, treatment and service and enhancing international academic influence are effective measures to accelerate the development of health services and deepen medical reforms.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM. METHODS: Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM. RESULTS: The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75-0.91) in the training set and 0.79 (0.65-0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74-0.93) and 0.82 (0.66-0.98), respectively. CONCLUSIONS The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
Humans ; Amino Acids ; Cysteine ; Cardiomyopathy, Hypertrophic/diagnosis* ; Biomarkers ; Proline ; Arginine ; Ornithine ; Glycine ; Choline