OBJECTIVE: Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC). METHODS: A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology. RESULTS: Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes. CONCLUSION Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology* ; Animals ; MicroRNAs/genetics* ; Lipopolysaccharides ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Ferroptosis/drug effects* ; Mice ; Myocytes, Cardiac/metabolism* ; Signal Transduction/drug effects* ; Rats ; Male ; Mice, Inbred C57BL ; Cardiomyopathies/etiology* ; Cell Line ; Sepsis/complications*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:Analyzed the clinicopathological features of thymoma with alopecia areata, and discussed the pathogenesis and treatment methods.Methods:The clinicopathologic data of patients with thymoma who underwent surgery from August 1, 2015 to July 31, 2020 in Beijing Tongren Hospital, Capital Medical University were reviewed. Transversally analyzed the patients of thymoma with alopecia areata and longitudinally compared with the patients of thymoma without alopecia areata after 1﹕10 matched by propensity score matching.Results:A total of 252 patients of thymoma were enrolled, including 6 patients with alopecia areata, accounting for 2.38%. The anti-AchR antibody, CD4 + /CD8 + T inversion in serum and myasthenia gravis were present in the all 6 thymoma patients with alopecia areata, which were significantly higher than those in the group of thymoma without alopecia areata. Besides myasthenia gravis, the proportion of complicated with other autoimmune diseases in thymoma patients with alopecia areata was significantly higher than that of thymoma patients without alopecia areata[83.33%(5/6) vs. 20.00%(12/60), P=0.003]. After operation, 5 patients’ alopecia areata were improved in 6 thymoma patients with alopecia areata(83.33%, 5/6). Conclusion:The thymoma patients with alopecia areata always complicated with myasthenia gravis and other autoimmune diseases. The pathogenesis may be associated with autoimmune CD8 + T lymphocytes produced by thymoma. At present, surgery is still the most effective way to improve thymoma-associated alopecia areata.

Objective: To investigate the clinical significance of pathological diagnosis and genetic abnormalities detection of gastrointestinal stromal tumor (GIST) using endoscopic biopsy. Methods: Patients with GIST diagnosed by endoscopic biopsy (from January 1st, 2016 to August 1st, 2018, at Zhongshan Hospital, Fudan University) were included in this study. This retrospective study evaluated the histopathologic and immunohistochemical (IHC) features, genetic abnormalities of the tumors and the treatment and clinical course of the patients. Results: Totally 4 095 cases of GIST were collected, among which 67 patients (67/4 095, 1.6%) underwent endoscopic biopsy. Forty-eight patients (71.6%) were male and 19 (28.4%) were female, with a mean age of 61 years (range 31-90 years). Fifty-nine lesions were located in stomach and eight in duodenum. Of all the 67 cases, 47 were spindle type, 14 were epithelioid type, and 6 mixed type. IHC staining showed the positive rates were 100.0% (64/64) for DOG1, 98.4% (62/63) for CD117, 87.5% (56/64) for CD34, 3.6% (2/56) for S-100 protein, 12.1% (7/58) for α-SMA, 12.3% (7/57) for desmin and 4.0% (2/50) for CKpan. Morphologically, 34 cases were malignant; three cases (all epithelioid type) were originally misdiagnosed as poorly differentiated carcinoma; missed-diagnosis were found in four cases (spindle type) due to the insufficient diagnostic tumor cells. The genetic abnormality detection rate in the biopsy tissue was 38.8% (26/67),among them two patients were lost to follow up after biopsy, 33 patients received surgical resection, 16 cases underwent operation after neoadjuvant therapy and 16 patients with advanced disease underwent continuous imatinib therapy, with the genetic testing rate of 6.1% (2/33), 10/16 and 14/16, respectively. Conclusions: Endoscopic biopsy is a useful but rare method for the preoperative diagnosis of GIST. For majority of biopsy, accurate pathological diagnosis and auxiliary examination can be completed to guide clinical treatment. A thorough history in combination with endoscopic finding is essential to avoid misdiagnosis (epithelioid type) and missed diagnosis (spindle type) in suspicious cases. Genetic testing should be recommended in patients who will undergo targeted therapy after endoscopic biopsy, and it can provide valuable information and guidance for clinical treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Gastrointestinal Stromal Tumors/pathology* ; Retrospective Studies ; Clinical Relevance ; Imatinib Mesylate ; Biopsy ; S100 Proteins

Objective:To explore the prognostic risk factors of thymoma patients after resection, and establish a novel nomogram to predict progression free survival(PFS) of patients with thymoma.Methods:A retrospectively analysis was performed on clinicopathological datas of 267 cases of thymoma patients underwent thymoma resection in Beijing Tongren Hospital from January 2010 to December 2019. The univariate and multivariate Cox risk ratio models were used to analyze the related factors that might affect PFS, and the prediction nomogram of PFS after thymoma resection was established using the screened independent risk factors. Then the predictive ability of the model was evaluated. Results:The univariate analysis showed that age, type of surgery, completeness of resection, WHO histologic classification, TNM stage and postoperative adjuvant therapy were significantly correlated with PFS after thymoma resection( P<0.05). The multivariate analysis showed that only age and TNM stage were independent prognostic factors affecting PFS after thymoma resection( P<0.05). The concordance index( C- index) of the prediction model for the prognosis of thymoma patients established by this method was 0.866(95% CI: 0.809-0.923), which had remarkable predictive efficiency. Conclusion:The nomogram model is constructed and verified based on age and TNM stage, excluding the interference of other clinicopathological factors on prognosis assessment, and which is convenient for clinicians to quickly and individually evaluate the prognosis of patients after thymoma resection.

Ethnic medicine has a rich history of application. Because of the large number of ethnic groups, wide geographical distribution, and unique medical systems in China, the research on the human use experience(HUE) of ethnic medicine should combine the characteristics of ethnic medicine, be based on practical experience, and respect folk practice and tradition. The clinical positioning of ethnic medicine should consider three factors, i.e., population region, dominant diseases, and clinical demand. We should consider the development of traditional preparations that meet the needs of ethnic regions and encourage the development of new drugs that can be popularized and used nationwide for the dominant diseases of ethnic medicines. Attention should be paid to the problems such as a large number of customary articles or substitutes of ethnic medicinal materials, the phenomena of foreign bodies with the same name and different names for the same substance, the different standards of medicinal materials, and the poor processing standards. The name, processing method, source, medicinal parts, and dosage of ethnic medicinal materials or decoction pieces should be determined, and resources should be carefully evaluated to ensure the safety of medicinal resources and ecology. The preparation of ethnic medicine is mostly in the form of pills, powder, ointment, etc., with simple processing technology. The problems of low-quality stan-dards of some preparations, different prescriptions with the same name, and inconsistent processing technology should be overcome, and the process route and main process parameters should be clarified to lay the foundation for the subsequent empirical research on HUE. In the collection and analysis of the HUE data of ethnic medicine, the core guiding ideology of "patient-centered" should be established, and the experience data of patients should be collected. The problems of weak links existing in the inheritance of ethnic medicine should be solved, and flexible and diverse methods should be adopted. Meanwhile, on the premise of complying with the requirements of the principles of medical ethics, we should respect the religion, culture, and customs of ethnic areas to obtain the key HUE information of ethnic medicine. On the basis of the patient preference information and differences in regional disease epidemiology, population characteristics, and medical practice, whether the HUE conclusions of ethnic medicine can be extrapolated to patients outside the region is evaluated from the aspects of clinical benefits, risk tolerance, risk acceptance, etc. The HUE research on ethnic medicine is carried out in a clear way to guide the research and development of new ethnic medicines.
Humans ; Medicine, Chinese Traditional ; China ; Reference Standards ; Technology ; Drugs, Chinese Herbal/therapeutic use*

Humans ; Gemcitabine ; Neoplasms

Objective:To investigate the clinical efficacy of radical resection of pancreatic cancer after neoadjuvant conversion therapy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 23 patients who underwent radical resection of pancreatic cancer after neoadjuvant conversion therapy in Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from January 2019 to May 2022 were collected. There were 17 males and 6 females, aged 58(range, 33-73)years. After neoadjuvant conversion therapy, the three-dimensional (3D) visualization was used to evaluate and classify tumor vascular invasion, and surgical plan was planned and implemented. Observation indicators: (1) situations of neoadjuvant conversion therapy; (2) surgical situations; (3) postoperative histopathological examination; (4) postoperative recovery; (5) follow-up. Measurement data with normal distribution were represen-ted as Mean± SD, and measurement data with skewed distribution were represented as M(range) or M( Q1, Q3). Count data were described as absolute numbers. Results:(1) Situations of neoadjuvant conversion therapy. All 23 patients received the AG combination chemotherapy (albumin-paclitaxel+gemcitabine), including 14 patients combined with stereotactic body radiation therapy. Of the 23 patients, 22 cases achieved partial response, and 1 case showed stable disease. The CA19-9 of the 23 patients was 85.06(29.74,634.5)U/mL and 13.96(9.74,25.02)U/mL before and after neoadjuvant conversion therapy, respectively. (2) Surgical situations. According to the results of preoperative 3D visualization of tumor vascular invasion, 7 of the 23 patients were evaluated as arterial invasion, 8 cases were evaluated as venous invasion, 5 cases were evaluated as arterial and venous invasion, and there were 3 cases showing negative of vascular invasion. Of the 23 patients, 12 cases underwent pancreaticoduodenectomy, 4 cases underwent radical antegrade modular pancreatosplenectomy, 7 cases underwent total pancreaticoduodenectomy. For vascular reconstruction, there were 10 patients without vascular reconstruction, and there were 13 patients undergoing artificial vascular vein reconstruction. The operation time and volume of intraoperative blood loss of the 23 patients was (524±171)minutes and 1 000(400,1 600)mL, respectively. (3) Postoperative histopathological exami-nation. Results of postoperative histopathological examination in 23 patients showed that there were 2 cases with moderate-well differentiated tumor, 10 cases with moderate differentiated tumor, 7 cases with moderate-poorly differentiated tumor, 2 cases with poorly differentiated tumor, and 2 cases negative of tumor. The number of lymph node dissected in 23 patients was 16±7. There were 5 cases with lymph node metastasis and 18 cases without lymph node metastasis. There were 17 cases with nerve invasion and 6 cases without nerve invasion. All 23 patients were negative of vascular invasion. Of the 23 patients, there were 21 cases with R 0 resection and 2 cases with R 1 resection. For pathological TNM staging, there were 2 cases with 0 stage, 13 cases with Ⅰ stage, 7 cases with Ⅱ stage, and 1 case with Ⅳ stage. For postoperative pathological scoring, there were 2 cases achieved 0 point (complete pathological remission), 16 cases achieved 2 points (partial remission), and 5 cases achieved 3 points (no significant effect). (4) Postoperative recovery. The postoperative duration of hospital stay of 23 patients was 19(14,31)days. There were 17 of 23 patients underwent postoperative complications, including 11 cases with Clavien-Dindo Ⅱ stage complications, 3 cases with Clavien-Dindo Ⅲa stage complications, 1 case with Clavien-Dindo Ⅲb stage complication, 1 case with Clavien-Dindo Ⅳ stage complication, and 1 case with Clavien-Dindo Ⅴ stage complica-tion. (5) Follow-up. There were 22 patients underwent follow-up, with follow-up time as 12(9,23)months. There were 9 patients underwent postoperative recurrence and metastasis, with recurrence and metastasis time as 7.8(range, 6.0-12.0)months. During the follow-up, 15 of the 22 patients survived. Conclusion:Radical resection of pancreatic cancer after neoadjuvant conversion therapy is feasible.

Objective:To compare the efficacy of cervical decompression performed at different times in the treatment of incomplete cervical spinal cord injury.Methods:A multicenter retrospective cohort study was conducted to analyze the clinical data of 96 patients with incomplete cervical spinal cord injury admitted to six hospitals including Honghui Hospital affiliated to Xi'an Jiaotong University, etc, from May 2018 to May 2021. There were 36 females and 60 males, aged 28-42 years [(35.2±6.7)years]. The injured segments were at C 3 in 7 patients, C 4 in 15, C 5 in 20, C 6 in 23 and C 7 in 31. According to the American Spinal Injury Association (ASIA) scale, there were 59 patients with grade B, 27 grade C, and 10 grade D. A total of 36 patients underwent cervical decompression within 24 hours after injury (early group), 33 patients within 24-72 hours after injury (late group), and 27 patients within 4-14 days after injury (delayed group). The operation time, intraoperative blood loss, postoperative drainage, length of hospital stay, Cobb angle, height of intervertebral space and space occupation of the spinal canal before surgery and at postoperative 3 days, and ASIA score, ASIA motor score, ASIA light tactile score, ASIA acupuncture sensation score, visual analog scale (VAS) score, Japanese Orthopedic Association (JOA) score, neck dysfunction index (NDI) before surgery and at postoperative 3 months, 1 year and at the last follow-up and incidence of complications were compared among the three groups. Results:All the patients were followed up for 12-21 months [(16.4±4.2)months]. There was no significant difference in the operation time among the three groups (all P>0.05). The intraoperative blood loss and postoperative drainage volume in the early group were (312.5±5.2)ml and (165.3±45.8)ml, which were higher than those in the late group [(253.5±40.0)ml, (120.4±60.6)ml] and the delayed group [(267.3±36.8)ml and (130.4±38.6)ml] (all P<0.01). There was no significant difference between the late group and the delayed group (all P>0.05). The length of hospital stay in the early group was (5.2±1.6)days, which was shorter than that in the late group [(7.6±2.3)days] and the delayed group [(8.0±1.3)days] (all P<0.05), but there was no significant difference between the late group and the delayed group ( P>0.05). There was no significant difference in the Cobb angle, height of intervertebral space and space occupation of the spinal canal among the three groups before and at postoperative 3 days (all P>0.05). There was no significant difference in the ASIA score, ASIA motor score, ASIA light tactile score, ASIA acupuncture sensation score, VAS score, JOA score and NDI among the three groups before surgery (all P>0.05). At postoperative 3 months, 1 year and at the last follow-up, the ASIA grading of the early group was better than that of the late group and the delayed group ( P<0.05 or 0.01), but there was no statistically significant difference between the late group and the delayed group (all P>0.05). The ASIA motor scores of the early group were (56.4±4.5)points, (76.3±3.6)points and (85.4±6.5)points at postoperative 3 months, postoperative 1 year and the last follow-up, respectively, which were higher than those in the late group [(52.3±2.4)points, (60.3±8.6)points and (72.3±2.4)points] and the delayed group [(51.9±2.3)points, (62.8±4.6)points and (71.9±1.3)points]; the ASIA light tactile scores of the early group were (70.2±2.9)points, (72.6±4.3)points and (78.3±2.3)points, which were higher than those in the late group [(66.2±3.7)points, (68.3±1.6)points and (73.3±1.6)points] and the delayed group [(65.2±2.1)points, (67.8±1.9)points and (72.3±2.5)points]; acupuncture sensation scores of the early group were (71.9±3.1)points, (80.1±3.8)points and (89.1±7.6)points, which were higher than those in the late group [(67.4±2.7)points, (72.6±3.7)points and (77.9±1.8)points] and the delayed group [(68.3±2.2)points, (72.6±3.1)points and (77.2±1.9)points] (all P<0.05). VAS scores of the early group at postoperative 3 months, 1 year and at the last follow-up were (4.3±0.6)points, (2.4±0.3)points and (1.6±0.2)points, which were lower than those in the late group [(5.1±1.3)points, (4.1±0.6)points and (3.0±0.6)points] and the delayed group [(5.0±1.7)points, (4.0±0.8)points and (3.1±0.2)points]; JOA scores of the early group were (12.8±1.6)points, (14.4±2.6)points and (17.9±3.3)points, which were higher than those in the late group [(11.9±1.9)points, (13.3±1.6)points and (8.9±1.3)points] and the delayed group [(11.6±1.8)points, (13.2±1.4)points and (9.3±2.1)points]; NDI scores of the early group were 12.1±3.3, 10.1±2.1 and 7.3±1.4, which were lower than those in the late group (14.4±3.1, 12.3±1.6 and 8.9±1.3) and the delayed group (14.1±2.3, 12.9±1.9 and 9.5±2.1) (all P<0.05). There was no significant difference in all the above-mentioned scores at postoperative 3 months, 1 year and at the last follow-up between the late group and the delayed group (all P>0.05). The incidence of complications was 25.0% (9/36) in the early group, 27.3% (9/33) in the late group and 37.0% (10/27) in the delayed group (all P>0.05). Conclusion:Compared with within 24-72 hours and 4-14 days after injury, cervical decompression performed within 24 hours after injury for patients with incomplete cervical spinal cord injury can shorten the length of hospital stay, improve the function of the spinal cord nerves and relieve pain, with no increase of the incidence of complications.

Aim To explore the mechanism of the natural phenolic compound pterostilbene(PTE)in the protection of liver ischemic/reperfusion. Methods A total of 40 C57 mice were divided into control group,model group,drug delivery group and treatment group and a 70% liver ischemic/reperfusion(ischemic 60 min)model was established,then primary LSECs were isolated by perfusion and digestion. Hepatic structural disruption was observed by HE staining. The ultrastructure of hepatic sinus endothelial cells was observed by transmission electron microscopy(TEM). The structure of LSECs fenestrae was observed by scanning electron microscopy(SEM). The expression level of heme oxygenase 1(HO-1)in LSECs was detected by Western blot. Results HE staining showed that PTE protected against hepatic ischemic injury. TEM observed that PTE had a protective effect on hepatic sinus endothelial cells,and the number of LSECs fenestrae in the blank control group was larger and the number of fenestrae in the liver I/R model group was reduced. The number of LSECs fenestrae in the liver I/R model group treated with PTE increased compared with the untreated liver I/R model group. Western blot result showed that PTE was able to induce HO-1 expression in LSECs. Conclusions PTE alleviates oxidative damage of endothelial cells in mouse hepatic sinus by inducing HO-1expression,and protects the liver from ischemia/reperfusion injury.