OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Objective To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion(OLIF),and put forward preventive measures.Methods From October 2015 to December 2019,23 patients who under-went reoperation after OLIF in four spine surgery centers were retrospectively analyzed.There were 9 males and 14 females with an average age of(61.89±8.80)years old ranging from 44 to 81 years old.The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases,discogenie low back pain in 1 case,degenerative lumbar spondylolisthesis in 6 cases,lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases.Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation.There were 17 cases of single fusion segment,2 of 2 fusion segments,4 of 3 fusion segments.All the cases underwent reoperation within 3 months after the initial surgery.The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy,cage adjustment and neurolysis in 2 cases,arthroplasty and neuroly-sis under endoscope in 1 case,posterior laminectomy and neurolysis in 1 case,pedicle screw adjustment in 1 case,exploration and decompression under percutaneous endoscopic in 1 case,interbody fusion cage and pedicle screw revision in 1 case.Visu-al analogue scale(VAS)and Oswestry disability index(ODI)index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up.During the follow-up process,the phenomenon of fusion cage settlement or re-displacement,as well as the condition of intervertebral fusion,were observed.The changes in in-tervertebral space height before the first operation,after the first operation,before the second operation,3 to 5 days after the second operation,6 months after the second operation,and at the latest follow-up were measured and compared.Results There was no skin necrosis and infection.All patients were followed up from 12 to 48 months with an average of(28.1±7.3)months.Nerve root injury symptoms were relieved within 3 to 6 months.No cage transverse shifting and no dislodgement,loosening or breakage of the instrumentation was observed in any patient during the follow-up period.Though the intervertebral disc height was obviously increased at the first postoperative,there was a rapid loss in the early stage,and still partially lost after reopera-tion.The VAS for back pain recovered from(6.20±1.69)points preoperatively to(1.60±0.71)points postoperatively(P＜0.05).The ODI recovered from(40.60±7.01)％preoperatively to(9.14±2.66)％postoperatively(P＜0.05).Conclusion There is a risk of reoperation due to failure after OLIF surgery.The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone,intraoperative endplate injury,significant subsidence of the fusion cage after surgery,postoperative fusion cage displacement,nerve damage,etc.As long as it is discovered in a timely manner and handled properly,further surgery after OLIF surgery can achieve better clinical results,but prevention still needs to be strengthened.

Objective:To explore the clinical application and triage management value of using blood circulating cell-free DNA (cfDNA) (cysteine dioxygenase type 1 gene, CDO1, and Homeobox protein A9 gene, HOXA9) hypermethylation level to detect and diagnose ovarian cancer.Methods:A case-control study was conducted on patients who went for surgery at Chengdu Womens and Childrens Central Hospital from November 2022 to October 2023. Blood samples were collected before surgery for evaluation of cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA) score, and DNA methylation testing. The basic clinical information, biomarkers, and transvaginal ultrasound (TVS) information were collected simultaneously. Information from a total of 151 patients was collected, including 122 cases with benign pathology and 29 ovarian cancer cases. The pathologic diagnosis of ovarian tissue was defined as the gold standard. The multivariate logistic regression analysis was used to identify high-risk factors for ovarian cancer. The clinical efficacy of DNA methylation detection for ovarian cancer was analyzed using the area under curve (AUC).Results:The results showed that the age, menopausal status, CA125 and HE4 detection, ROMA score, positivity rate of CDO1 gene and HOXA9 gene single or combined testing in ovarian cancer patients were higher than those in the benign group and showed significant differences ( P<0.05). Among these detection protocols, the AUC of CDO1 and HOXA9 dual gene methylation testing for ovarian cancer was the highest at 0.936 (95% CI, 0.878-0.994), with 89.7% (95% CI 73.6%-96.4%) sensitivity and 97.5% (95% CI 93.0%-99.2%) specificity, respectively. The positive detection rate of CDO1 and HOXA9 dual gene methylation in early ovarian cancer FOGO I-II stage is 12/14 higher than other tests. Conclusion:Blood cfDNA methylation detection, a simple, non-invasive, and highly sensitive detection method, is superior to the current ovarian cancer testing in the risk assessment and early detection.

Objective:To construct a diabetes foot prediction model for adult patients with type 2 diabetes based on retrospective cohort study using data from a regional health data platform.Methods:Using Yinzhou Health Information Platform of Ningbo, adult patients with newly diagnosed type 2 diabetes from January 1, 2015 to December 31, 2022 were included in this study and divided randomly the train and test sets according to the ratio of 7∶3. LASSO regression model and bidirectional stepwise regression model were used to identify risk factors, and model comparisons were conducted with net reclassification index, integrated discrimination improvement and concordance index. Univariate and multivariate Cox proportional hazard regression models were constructed, and a nomogram plot was drawn. Area under the curve (AUC) was calculated as a discriminant evaluation indicator for model validation test its calibration ability, and calibration curves were drawn to test its calibration ability.Results:No significant difference existed between LASSO regression model and bidirectional stepwise regression model, but the better bidirectional stepwise regression model was selected as the final model. The risk factors included age of onset, gender, hemoglobin A1c, estimated glomerular filtration rate, taking angiotensin receptor blocker and smoking history. AUC values (95% CI) of risk outcome prediction at year 5 and 7 were 0.700 (0.650-0.749) and 0.715(0.668-0.762) for the train set and 0.738 (0.667-0.801) and 0.723 (0.663-0.783) for the test set, respectively. The calibration curves were close to the ideal curve, and the model discrimination and calibration powers were both good. Conclusions:This study established a convenient prediction model for diabetic foot and classified the risk levels. The model has strong interpretability, good discrimination power, and satisfactory calibration and can be used to predict the incidence of diabetes foot in adult patients with type 2 diabetes to provide a basis for self-assessment and clinical prediction of diabetic foot disease risk.

Objective:To develop a prediction model for the risk of diabetic retinopathy (DR) in patients with newly diagnosed type 2 diabetes mellitus (T2DM).Methods:Patients with new diagnosis of T2DM recorded in Yinzhou Regional Health Information Platform between January 1, 2015 and December 31, 2022 were included in the study. The predictor variables were selected by using Lasso-Cox proportional hazards regression model. Cox proportional hazards regression models were used to establish the prediction model for the risk of DR. Bootstrap method (500 resamples) was used for internal validation, and the performance of the model was assessed by C-index, the receiver operating characteristic curve and area under the curve (AUC), and calibration curve.Results:The predictor variables included in the final model were age of T2DM onset, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, estimated glomerular filtration rate, and history of lipid-lowering agent and angiotensin converting enzyme inhibitor uses. The C-index of the final model was 0.622, and the mean corrected C-index was 0.623 (95% CI: 0.607-0.634). The AUC values for predicting the risk of DR after 3, 5, and 7 years were 0.631, 0.620, and 0.624, respectively, with a high degree of overlap of the calibration curves with the ideal curves. Conclusion:In this study, a simple and practical risk prediction model for DR risk prediction was developed, which could be used as a reference for individualized DR screening and intervention in newly diagnosed T2DM patients.

Objective:To construct a risk prediction model for diabetes kidney disease (DKD).Methods:Patients newly diagnosed with type 2 diabetes mellitus (T2DM) between January 1, 2015, and December 31, 2022, were selected as study subjects from the Yinzhou Regional Health Information Platform in Ningbo City. The Lasso method was used to screen the risk factors, and the DKD risk prediction model was established using Cox proportional hazard regression models. Bootstrap 500 resampling was applied for internal validation.Results:The study included 49 706 subjects, with an median ( Q1, Q3) age of 60.00 (50.00, 68.00) years old, and 55% were male. A total of 4 405 subjects eventually developed DKD. Age at first diagnosis of T2DM, BMI, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, past medical history (hyperuricemia, rheumatic diseases), triglycerides, and estimated glomerular filtration rate were included in the final model. The final model's C-index was 0.653, with an average of 0.654 after Bootstrap correction. The final model's area under the receiver operating characteristic curve for predicting 4-year, 5-year, and 6-year was 0.657, 0.659, and 0.664, respectively. The calibration curve was closely aligned with the ideal curve. Conclusions:This study constructed a DKD risk prediction model for newly diagnosed T2DM patients based on real-world data that is simple, easy to use, and highly practical. It provides a reliable basis for screening high-risk groups for DKD.

Objective To investigate the effect and mechanism of proteasome inhibitor MG132 on memory impairment induced by chronic hypoxia in mice.Methods(1)A hypoxic model of the mouse midbrain dopaminergic neuron cell line MN9D was established using a hypoxia workstation.To observe the effects of hypoxia on the expression of TH,Ub-K48 and Ub-K63,MN9D cells were divided into normoxia group and hypoxia(12 h,24 h and 48 h)groups.To observe the effects of MG132 on the expression of the above-mentioned proteins,MN9D cells were divided into normoxia group,hypoxia group and hypoxia + MG132(25,50,100,200 μmol/L)group.(2)A mouse model of memory impairment was established using a hypobaric chamber.To observe the effects of hypobaric hypoxia on the expression of TH,Ub-K48 and Ub-K63 in the substantia nigra compacta(SNc)of mice,thirty C57BL/6 mice were randomly and equally divided into normoxia group and hypobaric hypoxia(3 d and 21 d)groups,10 in each group.To observe the effects of MG132 on spatial memory impairment induced by hypobaric hypoxia,twenty-four C57BL/6 mice were randomly and equally divided into normoxia group,hypobaric hypoxia 21 d group and hypobaric hypoxia 21 d+MG132 group,8 in each group.(3)The protein expression levels of TH,Ub-K48,and Ub-K63 in MN9D cells which were either subjected to different durations of hypoxia treatment or pre-treated with MG132 prior to hypoxia treatment were detected using Western blotting(WB).The novel object recognition test was used to detect the memory function of mice.Immunofluorescence was used to detect the proportion of positive immunoreactive area of TH response in the SNc region.The expression levels of TH,Ub-K48,and Ub-K63 in the SNc region were detected by WB.Results(1)Compared with normoxia group,MN9D cells in hypoxia 24 h group showed increasing expression of Ub-K48 and Ub-K63(P<0.05),and decreasing expression of TH(P<0.05),and MN9D cells in all hypoxia groups showed increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05).Compared with hypoxia group,MN9D cells showed decreasing expression of Ub-K48/TH and Ub-K63/TH in hypoxia + MG132 100 umol/L group and hypoxia + MG132 200 umol/L group(P<0.05).(2)Compared with the mice in normoxia group,mice in 3 d and 21 d hypobaric hypoxia groups showed decreasing expression of TH(P<0.001),and increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05)in the SNc region.Compared with normoxia group,the mice in 21 d hypobaric hypoxia group showed a lower new object recognition index(P<0.01),and the proportion of positive immunoreactive area of TH response in the SNc region(P<0.05).Compared with 21 d hypobaric hypoxia group,the mice in hypobaric hypoxia 21 d+MG132 group showed a higher new object recognition index(P<0.01).Conclusion The proteasome inhibitor MG132 could alleviate the memory impairment induced by chronic hypoxia in mice,and its mechanism may be related to the inhibition of Ub-K63 and Ub-K48,which in turn upregulates expression of TH in dopaminergic neurons.

The pathogenesis of Alzheimer's disease(AD)is complex and unclear.Existing drugs can only alleviate its symp-toms,and there is an urgent need to develop effective therapeutic drugs.As the representative drugs of tonic and enlightening medicine,ginseng and acorus calamus have pharmacological effects to improve memory,improve learning ability and reduce cognitive impairment,which are commonly used in Chinese med-icine for the treatment of dementia.The combination of ginseng and acorus calamus can further promote the active ingredients in-to brain to exert their medicinal effects,and delay the process of AD through anti-inflammatory,anti-oxidative stress,modulation of neuronal-synaptic plasticity and other multiple pathways,with multi-level,multi-system and multi-target action characteristics.This paper attempts to summarize the existing research results and lay the foundation for further exploring the synergistic mech-anism of action of ginseng-acorus calamus combination and the dose-effect relationship of the combination,so as to provide a sci-entific basis for the development of innovative Chinese medicines for the prevention and treatment of AD.

Objective To explore training programs for pharmacists in retail pharmacies to implement medication therapy management services for patients with chronic diseases.Methods Combined with national conditions in China,the expert consultation method was used to establish a training program for pharmacists in retail pharmacies on chronic disease medication therapy management in terms of curriculum setting,teaching mode,and teaching assessment,and to implement the training.Qualitative interviews were conducted to gain an in-depth understanding of pharmacists'evaluations and suggestions on the training program.Results The training curriculum covered practice skills of pharmaceutical care and pharmacotherapeutics.The teaching modes included online learning and Q&A,case writing,role-playing and standardized patient case practices,and teaching assessment was conducted through knowledge quizzes,objective structured clinical exams,practice tests and questionnaires.181 pharmacists attended and completed the training,and the score of their overall satisfaction with the training program was 4.7(out of a maximum score of 5.0).Through the training,pharmacists'knowledge and skill levels in medication therapy management as well as attitudes,confidence and perceptions of practice were significantly improved and demonstrated better pharmacy practice abilities.Most pharmacists expressed their learning needs for disease-based pharmacy service model and communication skills training with patients in qualitative interviews.Conclusion A training program suitable for retail pharmacists to improve the comprehensive ability of chronic disease medication therapy management has initially formed,and disease-based doctor-patient communication ability and pharmaceutical care process training should become the focus of learning in medication therapy management service ability of retail pharmacists.

Objective:To systematically integrate the disease experience of patients with systemic lupus erythematosus, and to provide evidence-based evidence for the formulation of health management programs based on the psychological experience of patients with systemic lupus erythematosus.Methods:Qualitative studies on psychological experience of patients with systemic lupus erythematosus were searched by computer in PubMed, Cochrane Library, CINAHL, Embase, Web of Science, ProQuest, CNKI, Wanfang Database, VIP and China Biology Medicine disc. The search period was from the establishment of the databases to July 2023. The quality of literature was evaluated using the Quality Evaluation Criteria (2020) of Evidence-Based Health Care Center of Joanna Briggs Institute, Australia, and the results of literature studies were integrated by Meta integration method.Results:A total of 13 articles were included, 48 research results were extracted and eight categories were summarized, ultimately forming three integrated results including "negative psychological experience", "increased disease demand" and "active regulation strategies".Conclusions:Medical staff should pay attention to the physical and mental feelings of patients with systemic lupus erythematosus during the disease process and provide targeted and effective intervention strategies in clinical practice to alleviate their negative emotions and improve their quality of life.