OBJECTIVE To investigate the in vitro anti-inflammatory effects and mechanisms of oblongifolins A （OA） extracted from Garcinia oblongifolia. METHODS RAW264.7 cells were used as the research subject and divided into control group （0.5% DMSO）， lipopolysaccharide （LPS） group （1 μg/mL）， DEX group （10 µmol/L DEX+1 μg/mL LPS）， and low-， medium-， and high-concentration groups of OA （7.5， 15， 30 µmol/L OA+1 μg/mL LPS）. Except for the control group， the remaining groups were first stimulated with LPS for 1 hour and then mixed with drugs for 24 hours. The morphological changes of cells were observed in each group. The contents of nitric oxide （NO）， reactive oxygen species （ROS）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， IL-4 and IL-10 were detected in cells of each group； mRNA expression levels of TNF-α， IL-6 and IL-1β were measured. The expression of key proteins in the nuclear factor κB （NF-κB） and nuclear factor-erythroid 2-related factor 2 （Nrf2） signaling pathways in each group， as well as the nuclear translocation of NF-κB p65 and Nrf2 proteins in control group， LPS group and OA high-concentration group， were detected. RESULTS Compared to the LPS group， the number of spindle-shaped and irregular cells gradually decreased in OA groups， the contents of NO， ROS （except for OA low-concentration group）， TNF-α， IL-6 and IL-1β， the mRNA expressions of TNF-α， IL-6 （except for OA low-concentration group） and IL-1β as well as the protein expressions of phosphorylated NF-κB p65 （p-NF-κB p65）， p-IκBα， and Kelch-like ECH-associated protein 1 （Keap1） were decreased significantly （P＜0.05）. The contents of IL-4 and IL-10， protein expressions of IκBα， Nrf2 （except for OA low- and medium-concentration groups）， HO-1 （except for OA low-concentration group） and NQO1 were all increased significantly （P＜0.05）. OA of high concentration could inhibit NF-κB p65 protein nuclear translocation and promote Nrf2 protein nuclear translocation. CONCLUSIONS OA can suppress LPS-induced inflammation in RAW264.7 macrophages. The underlying molecular mechanism likely entails the inhibition of the NF-κB signaling pathway， the activation of the Nrf2 signaling pathway and the reduction of ROS and inflammatory factor release.

Objective To investigate the effect of oral fish oil on wound healing and related indexes in patients with diabetic foot ulcer(DFU).Methods A randomized,double-blind,placebo-controlled design was used to recruit 68 patients with DFU aged 18-80 years old in the hospital,and the baseline clinical data of the patients were collected.The patients were randomly divided into experimental group(32 cases,fish oil soft capsule,3 g/d)and control group(33 cases,corn oil soft capsule,3 g/d)by random number generated by Ex-cel,and the intervention lasted for 12 weeks.The primary endpoints included the proportion of complete wound healing and healing area≥50%.The secondary endpoints included wound area,healing time,inflamma-tion index,glucose metabolism index,nutrition related index and wound reinfection.Additionally,the influen-cing factors of wound healing were analyzed.Results After intervention,the proportion of complete wound healing and healing area≥50%in the experimental group was significantly higher than that in the control group(P=0.007,0.039).In the subjects with complete wound healing,the mean healing time in the experi-mental group was shorter than that in the control group,but the difference was not statistically significant(P=0.132).The reduction area of wound area in the experimental group was significantly larger than that in the control group(P=0.045).The decrease of interleukin(IL)-6 and IL-8 in the experimental group was significantly higher than that in the control group(P<0.05).There was no significant difference in the reduc-tion of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),neutrophil-to-lymphocyte ratio(NLR),glycated hemoglobin A1c(HbA1c)and platelet-to-lymphocyte ratio(PLR)between the two groups(P>0.05).The improvement of prealbumin(PA)in the experimental group was higher than that in the control group,but the difference was not statistically significant(P>0.05).Multivariate logistic regression analysis showed that oral fish oil intervention(OR=6.771,95%CI:1.787-25.652),HbA1c(OR=4.149,95%CI:1.026-16.770)and ulcer type(OR=4.319,95%CI:1.026-18.173)were the influencing factors of wound healing(P<0.05).Conclusion Oral fish oil promotes wound healing in patients with DFU,which may be re-lated to improving the level of chronic inflammation in the body.

Objective:To summarize the best evidence for the application of massage in the management of meibomian gland dysfunction (MGD) -related dry eye.Methods:A systematic search was conducted in databases and websites including UpToDate, BMJ Best Clinical Practice, Joanna Briggs Institute Evidence-Based Healthcare Center database, National Guideline Clearinghouse, Medlive, PubMed, China National Knowledge Infrastructure, and WanFang data. The search covered literature on massage for MGD-related dry eye, including clinical decisions, best practices, evidence summaries, guidelines, expert consensus, systematic reviews, and randomized controlled trials. The search period extended to December 2023. Two researchers independently evaluated the quality of the literature and extracted and summarized the evidence.Results:A total of nine articles were included: three guidelines, four expert consensus papers, and two systematic reviews. Twenty-five pieces of best evidence were summarized from six aspects: massage practitioners, massage methods and indications, massage instruments and devices, massage duration and frequency, combination therapy, and the safety and efficacy of massage.Conclusions:This study summarizes the best evidence for applying massage in MGD-related dry eye. It is recommended that healthcare professionals apply this evidence in combination with clinical context and patient preferences.

Objective:To explore the changes of large-scale functional brain networks and network topological properties in patients with major depressive disorder (MDD) whose diagnosis had not changed after 5 years of follow-up.Methods:Totally 521 cases of hospitalized MDD patients were recruited from January 2012 to August 2018, and another 204 cases of gender- and age-matched healthy controls were recruited. All participants completed resting-state functional magnetic resonance scanning and clinical assessment. Their diagnosis were reviewed 5 years after discharge.A total of 258 participants whose diagnosis had not changed were counted into the MDD group for analysis. The differences in large-scale brain network connectivity between the two groups were analyzed by constructing a whole-brain functional network, on the basis of which the altered topological properties of the sensorimotor network (SMN), visual network (VN) and default mode network (DMN) were further analyzed between the two groups.The SPSS 24.0 software was used for data analysis and the independent sample t-test and χ2 test were used for the data comparison of the two groups. Results:Compared with the healthy controls, the MDD group had significantly decreased network clustering, mainly involving the SMN, VN and DMN (edge P<0.001, cluster P<0.05). The MDD group had decreased functional connectivity(FC) strength within the SMN, VN and DMN networks, the FC strength between the SMN and VN networks, between the frontoparietal network (FPN) and the DAN networks were decreased(all P<0.05, FDR corrected). Graph-theory analysis showed that local efficiency, clustering coefficient, and normalized shortest path length were decreased in the MDD group, node efficiency was decreased in the left ventral medial prefrontal cortex and the middle of the bilateral insula, node centrality was decreased in the middle of the bilateral insula and occipital lobe, and the betweenness was decreased in the middle of the right insula (all P<0.05, FDR corrected). Conclusion:MDD exhibits abnormal network functional connectivity, disruption of network topological properties, diminished optimal information processing, and to some extent reflects the severity of depressive symptoms. The decreased ability of information transfer flow in the insula plays an important role for the functional abnormality of the network.

Objective To explore the predictive value of serum homo sapiens microRNA(hsa-miR)-30c-5p expression in patients with type 2 diabetes mellitus(T2DM)for microvascular complications.Methods A total of 205 T2DM patients admitted to Bazhong Central Hospital from May 2021 to September 2022 were selected as the diabetes group,and the diabetes group was further divided into diabetes with combined group(n=124)and non combined group(n=81)according to the microvascular complications of the patients.In addition,205 healthy people who underwent physical examination during the same period were selected as the control group.The expression of hsa-miR-30c-5p in serum was detected by reverse transcription-polymerase chain reaction(RT-PCR)and compared.The factors affecting microvascular complications were analyzed using multivariate logistic regression analysis,and receiver operating characteristic(ROC)curves were plotted to predict the value of serum hsa-miR-30c-5p expression in predicting microvascular complications in T2DM patients.Results The expression of serum hsa-miR-30c-5p in the combined group(0.58±0.06)and the non-combined group(0.72±0.08)were lower than that in the control group(0.89±0.21),and the differences were significant(t=16.038,7.079,all P=0.001).The combined group was lower than the non-combined group,and the difference was significant(t=14.289,P=0.001).The course of diabetes[(OR(95％CI):3.873(2.976～4.770)],uric acid[(OR(95％CI):2.125(1.211～3.040)]and glycosylated hemoglobin[(OR(95％CI):2.680(1.745～3.616)]were independent risk factors for microvascular complications in T2DM patients(all P＜0.05),while the time within the target range of glucose[(OR(95％CI):0.491(0.135～0.846)]and serum hsa-miR-30c-5p[(OR(95％CI):0.532(2.976～4.770)]were protective factors for microvascular complications in T2DM patients(all P＜0.05).The sensitivity,specificity and area under the curve(95％CI)of serum hsa-mir-30c-5p expression in predicting microvascular complications in T2DM patients were 81.45％,85.19％and 0.802(0.741～0.854),respectively.Conclusion The expression of serum hsa-miR-30c-5p in patients with T2DM is abnormally reduced,and serum hsa-miR-30c-5p is a protective factor for microvascular complications in patients with T2DM.It may have a certain predictive value for microvascular complications in patients with T2DM.

Objective To explore the health-related quality of life(HRQOL)among patients with multidrug-resistant and rifampin-resistant pulmonary tuberculosis(MDR/RR-PTB)and analyze its influencing factors.Methods Data was collected from 50 MDR/RR-PTB patients registered for treatment management in the"Tuberculosis Management Information System"in Bazhong City from 2021 to 2024 as resistance group.Fifty pulmonary tuberculosis patients sensitive to anti-tuberculosis drug treatment registered in the system during the same period were selected as control group.A cross-sectional survey method was employed using the quality of life instruments for chronic disease pulmonary tuberculosis(QLICD-PT)to measure and compare the HRQOL between two groups.Multiple linear regression analysis was used to analyze factors affecting the HRQOL of MDR/RR-PTB patients.Results Except for physiological function,there were statistically significant difference between MDR/RR-PTB group and control group in terms of total quality of life score,psychological function,social function,and specific modules(P＜0.05).Univariate analysis showed that there were statistically significant differences in the total quality of life scores among patients with different genders,medical insurance statuses,monthly family income situations,presence or absence of comorbidities,lymphocyte count,albumin,C-reactive protein,and body mass index(P＜0.05).Multiple linear regression analysis revealed that(P＜0.05)there was significant difference for the partial regression coefficient tests of patient's medical insurance and monthly family income situations(P＜0.05).Conclusion The HRQOL of MDR/RR-PTB patients is lower than that of pulmonary tuberculosis patients sensitive to anti-tuberculosis drugs.The patient's health insurance and monthly family income are potential factors affecting the HRQOL of MDR/RR-PTB patients.

Background/Aims: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. Methods: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options. Results: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018–1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048– 1.357). On the other hand, CFHR1 (0.621, 0.497–0.776) and CFHR2 (0.824, 0.703–0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707–0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036–1.314). Additionally, C1S (0.111, 0.018–0.672), C7 (1.631, 1.190–2.236), and CFHR2 (1.279, 1.059–1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network. Conclusions Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.

Objective:To explore the differences in clinicopathological features, survival status and prognostic influencing factors of breast cancer patients with different molecular subtypes, and to provide bases for the prevention and treatment of breast cancer.Methods:The clinicopathological data of new-onset female breast cancer patients hospitalized in Shanxi Province Cancer Hospital from January 2015 to December 2016 were retrospectively analyzed, and patients were followed up. The clinicopathological features of patients with different molecular subtypes were compared. The follow-up was performed until June 30, 2021. Kaplan-Meier method was used to analyze the survival of patients, and Cox proportional hazards model was used to analyze the factors affecting overall survival (OS) of patients with different molecular subtypes.Results:There were 272 (14.9%), 1 005 (55.2%), 277 (15.2%) and 268 (14.7%) patients with subtypes of Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative breast cancer (TNBC), respectively. The differences in the distribution of patients with age at diagnosis, age at menarche, menopausal status, age at menopause, pathological type, longest tumor diameter, T staging, N staging, histological grading, and TNM staging were statistically significant among the four groups (all P < 0.05). At a median follow-up of 60 months, the 5-year OS rates of Luminal A, Luminal B, HER2 overexpression and TNBC subtypes were 93.8%, 89.2%, 77.6% and 78.0%, respectively, and the difference was statistically significant ( χ2 = 58.76, P < 0.001). M staging was an independent influencing factor for OS in patients with Luminal A breast cancer ( HR = 16.789, 95% CI 4.972-56.690, P < 0.001); T staging ( HR = 2.721, 95% CI 1.715-4.319), N staging ( HR = 4.460, 95% CI 2.399-8.291) and M staging ( HR = 3.364, 95% CI 1.988-6.670) were independent influencing factors for OS in patients with Luminal B breast cancer (all P < 0.001); N staging ( HR = 4.428, 95% CI 1.836-10.677) and M staging ( HR = 13.489, 95% CI 6.043-30.107) were independent influencing factors for OS of patients with HER2 overexpression breast cancer (both P < 0.01); T staging ( HR = 3.052, 95% CI 1.575-5.915), N staging ( HR = 2.492, 95% CI 1.298-4.785) and M staging ( HR = 33.012, 95% CI 8.606-126.637) were independent influencing factors for OS of patients with TNBC (all P < 0.01). Conclusions:The clinicopathological features and prognostic influencing factors of breast cancer patients with different molecular subtypes are different, and the prognosis of HER2 overexpression and TNBC patients is poor. Clinicians should provide individualized treatment and follow-up programs for patients with different molecular subtypes of breast cancer.

The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

Objective:To evaluate the effect of teacher simulate standardized patient (TSSP) consultation training in pediatric practical teaching.Methods:A total of 120 interns from the five-year clinical medicine major of Batch 2015 were randomly divided into experimental group and control group. In the experimental group, 60 interns were trained by TSSP for consultation after admission. After the training, the clinical parents of the children were consulted and the children were physically examined under the guidance of teachers. In the control group, 60 interns were trained according to the same requirements, but TSSP consultation training was not included. At the end of the practice, the performance, operation skills and medical record writing ability of the interns were compared, and the satisfaction of the experimental group was investigated. SPSS 25.0 software was used for t test and chi-square test. Results:The medical record writing results of the experimental group were (96.15±3.00) points, significantly higher than that of the control group [(81.02±3.29) points], and the differences were statistically significant ( t = 26.38; P < 0.001). In the mini-clinical evaluation exercise (Mini-CEX), the scores of medical history collection, communication skills, humanistic care and physical examination were significantly higher than those of the control group ( t= 15.41, 17.67, 15.39 respectively; all P < 0.001). The experimental group had high satisfaction with the teaching method of TSSP consultation training. Conclusion:TSSP consultation training improves the intern medical record writing ability, doctor-patient communication ability, clinical operation ability, stimulates the learning interest of interns, trains the trainee doctors humanistic consciousness, integrates into the ideological and political education, effectively ensures the quality of practical teaching of pediatrics, and obtains recognition from intern, which is worth promoting.