This paper summarizes Professor LU Fang's clinical experience in treating systemic lupus erythematosus （SLE） based on the differentiation and treatment of heat-toxin and blood-stasis in the collaterals. SLE is generally characterized by deficiency in origin with excess in manifestation. The core pathogenesis is heat-toxin obstructing the collaterals. During the acute active stage， the predominant pattern is blazing heat-toxin causing blood stasis， while in the chronic remitting stage， the main pattern is toxic stasis blocking the collaterals with qi and yin deficiency. Clinical treatment follows the basic principle that treat with salty-cold herbs， when heat invades internally and that assist with acrid-dispersing herbs when stasis obstructs the collaterals. The self-formulated Yimian Decoction （抑免汤） serves as the base formula and is applied in stages. During the acute active stage， it is often combined with herbs for clearing heat and detoxifying， cooling blood and resolving stasis， and unblocking the collaterals. In the chronic remitting stage， it is often combined with herbs for activating blood circulation and unblocking the collaterals， as well as tonifying qi and nourishing yin.

Platelet is the key factor in hemostasis and coagulation,its potential in inflammatory response and immune response has been widely concerned in recent years.A growing number of studies indicate that tissue damage in inflammatory bowel disease is not only the result of dysregulated immune response,but also the active participation of various other cellular systems,and platelet might play an important role in intestinal mucosal inflammation and immunity.This article reviewed the abnormal changes and possible mechanisms of platelet in inflammatory bowel disease,and the prospects of platelet as a specific treatment target for inflammatory bowel disease.

Objective To observe the expression of A kinase interacting protein 1(AKIP1)in cervical cancer and analyze the correlation between AKIP1 and clinicopathological features and prognosis.Methods A total of 88 patients with cervical cancer admitted to the Second People's Hospital of Liaocheng from January 2016 to December 2018 were selected for the study.The expression of AKIP1 was detected by immunohistochemical staining,and its expression was judged to be negative or positive according to the score of staining results.The relationship between AKIP1 expression and clinicopathological features was analyzed by x2test;Kaplan-Meier curve was used to analyze the effect of AKIP1 on the prognosis of cervical cancer.Results Compared with the para-cancer tissues,the expression of AKIP1 was significantly increased in cervical cancer(P＜0.05);Patients with tumor diameter ≥4 cm,low differentiation,lymph node metastasis and FIGO stageⅡ-Ⅲ,the positive rate of AKIP1 was significantly higher than that of patients with tumor diameter＜4 cm,high differentiation,no lymph node metastasis and FIGO stage I,the difference is statistically significant(P＜0.05);Kaplan-Meier analysis showed that the survival rate of AKIP1 positive patients was significantly lower than that of AKIP1 negative patients(x2=5.162,P＜0.05).Conclusion The expression of AKIP1 is correlated with poor clinicopathologic features in patients with cervical cancer,and may be a biological marker affecting the prognosis of patients with cervical cancer.

Objective This study aimed to assess the clinical efficacy of Shenling Baizhu Granules in treating low anterior resection syndrome(LARS)in rectal cancer.Methods The study employed a randomized,double-blind,placebo-parallel controlled,single-center,validity-tested clinical trial design.December 2019 to June 2022,the Department of Gastrointestinal Surgery and Integrated Traditional Chinese and Western Medicine of Peking University First Hospital recruited 110 patients who had undergone low anterior resection(LAR)for rectal cancer and subsequently developed LARS.These patients,meeting the enrollment criteria,were randomly assigned into the treatment group(55)and the control group(55)using the double-blind method principle.The randomization table was generated by SAS 9.2 software employing the double-blind method.The treatment group received oral Shenling Baizhu Granules,while the control group received oral placebo granules.Both groups commenced treatment on the 10th day after-surgery for 30 consecutive days.Patients were evaluated using LARS score,traditional Chinese medicine(TCM)symptom grading,and XU Zhongfa score before treatment,on the 15th day of treatment,and on the 1st day after treatment cessation.Results Out of 110 patients,107 were included in the full analysis set for efficacy analysis:55 patients in the treatment group and 55 patients in the control group.One case in the treatment group was excluded(against protocol),and two cases in the control group were excluded(one lost to follow-up,one against protocol).Baseline data between the two groups were consistent,with no statistically significant difference.Before treatment,LARS scores for the treatment and control groups were 33.0(31.0,36.0)and 34.0(32.0,37.0)respectively.Patients with TCM symptom scores of grades 2 to 3 accounted for 92.73％and 90.57％in the treatment and control groups,respectively,with no statistically significant difference.After 30 days of treatment,LARS scores for the treatment and control groups were 21.0(19.8,23.0)and 26.0(22.0,28.0)respectively.The percentage of patients with TCM symptom scores of grades 2 to 3 decreased to 33.33％in the treatment group and 66.04％in the control group,with a statistically significant difference.Shenling Baizhu Granules showed rapid improvement in watery or loose stools in post-operative rectal cancer patients.After 30 days of treatment,Shenling Baizhu Granules significantly improved appetite,stool consistency,abdominal distension,abdominal pain,and eructation symptoms in postoperative rectal cancer patients.Before treatment,the XU Zhongfa scores for the treatment and control groups were 3.0(2.0,4.3)and 4.0(2.0,4.0)respectively,with no statistically significant difference.After 30 days of treatment,the XU Zhongfa scores for the treatment and control groups were 7.0(6.0,8.0)and 6.0(5.0,7.0)respectively,with the treatment group significantly higher than the control group(P＜0.01).Conclusion Shenling Baizhu Granules can effectively improve LARS symptoms in patients following LAR of rectal cancer within a short period of time.

Objective:To evaluate whether additional radical surgery is necessary following non-curative endoscopic resection of early colorectal cancer.Method:Clinicopathological data in 104 patients following non-curative endoscopic resection of early colorectal coucer at the Department of General Surgery, Peking University First Hospital between Jan 2011 and Dec 2021.Results:Lymph node metastasis and/or residual cancer was found in 23 patients (22%), including 12 cases of lymph node metastasis, 7 cases of residual cancer and 4 patients with both residual cancer and lymph node metastasis. Univariate analysis indicated that vascular infiltration, positive vertical margin, and female gender were risk factors for lymph node metastasis. Risk factors for residual cancer were tumors ≥2 cm in size, negative lift sign, infiltration depth of ≥1 000 μm, and positive horizontal and vertical margins. Multivariate Logistic regression analysis revealed that vascular invasion, positive vertical margins, and being female were independent risk factors for lymph node metastasis, while positive vertical margins was independent risk factor for residual cancer. Salvage surgery lasted for a median of 184 (156-233) minutes, with an estimated blood loss of 50 (20-100) ml and an average postoperative hospital stay of 9 (8-11) days. Seven cases of Clavein-Dindo Ⅱ or higher complications were observed, including pulmonary embolism in 1 case , anastomotic leakage in one, lymphatic fistula in one, bowel obstruction in 2 cases and urinary tract infection in 2 cases.Conclusion:Salvage surgery is mandatory for early endoscopic non-curative resection of colorectal cancer.

Objective:To evaluate the role of mitochondria-associated endoplasmic reticulum membranes (MAMs) regulated by protein tyrosine phosphatase interacting protein 51 (PTPIP51) in sevoflurane-induced necroptosis in hippocampal neurons of rats using the in vitro experiment.Methods:Primary cultured hippocampal neurons from fetal rats of Sprague-Dawley rats were inoculated in culture wells (100 μl/well ) or culture flasks (3 ml/bottle) at a density of 5×10 5 cells/ml at 7 days of culture and divided into 4 groups ( n=19 each) using a random number table method: control group (C group), sevoflurane group (Sev group), sevoflurane+ siRNA-PTPIP51 transfection group (Sev+ siPTPIP51 group), and sevoflurane+ nonsense siRNA transfection group (Sev+ siNC group). The neurons were placed in a culture incubator containing 2% sevoflurane and incubated at 37 ℃ for 5 h in Sev, Sev+ siPTPIP51 and Sev+ siNC groups. Then neurons were collected for determination of the cell survival rate (by MTT method), cytoplasmic calcium concentration ([Ca 2+ ] i) and necroptosis rate (by flow cytometry), expression of PTPIP51, receptor-interacting protein kinase 1 (RIPK1), RIPK3, and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) (by Western blot) and for microscopic examination of the partial length, endoplasmic reticulum circumference, and mitochondrial circumference of MAMs (with a transmission electron microscope). Results:Compared with group C, the activity of neurons was significantly decreased, the [Ca 2+ ] i and necroptosis rate were increased, the expression of PTPIP51, RIPK1, RIPK3 and p-MLKL was up-regulated, and the ratio of partial length of MAMs to endoplasmic reticulum perimeter and partial length of MAMs to mitochondrial perimeter were increased in group Sev ( P<0.05). Compared with group Sev, the activity of neurons was significantly increased, the [Ca 2+ ] i and necroptosis rate were decreased, the expression of PTPIP51, RIPK1, RIPK3 and p-MLKL was down-regulated, and the ratio of partial length of MAMs to endoplasmic reticulum perimeter and partial length of MAMs to mitochondrial perimeter were decreased in group Sev+ siPTPIP51 ( P<0.05), and no statistically significant changes were found in the above parameters in group Sev+ siNC ( P>0.05). Conclusions:Up-regulation of PTPIP51 expression mediates structural changes in MAMs and is involved in the process of sevoflurane-induced necroptosis in hippocampal neurons of rats.

Objective:To investigate the expression levels of miRNA-21 (miR-21) and miRNA-330 (miR-330) in serum exosomes of non-small cell lung cancer (NSCLC) patients with brain metastases, and the correlation of the two with the prognosis of patients.Methods:A prospective cohort study was conducted. A total of 125 NSCLC patients who were admitted to the Affiliated People's Hospital of Shandong First Medical University from March 2021 to September 2022 were prospectively selected, and the brain metastasis was determined by CT, contrast-enhanced magnetic resonance imaging of the head, or surgical pathology. The NSCLC patients were divided into the metastatic group (58 cases) and the non-metastatic group (67 cases) according to whether they had brain metastases, and 50 patients with benign lung diseases and 50 healthy subjects who underwent physical examination in the same period were selected as benign group and healthy control group respectively. Serum samples were collected from all subjects (including patients' pre-treatment samples), the exosomes were extracted, and real-time fluorescence quantitative polymerase chain reaction was used to determine the relative expression of miR-21 and miR-330 in exosomes at the transcriptional level, and electrochemiluminescence immunoassay was used to detect the levels of serum tumor markers [neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA)]. The levels of miR-21 and miR-330 in serum exosomes and serum tumor markers in the 4 groups were compared, and the correlation between miR-21 and miR-330 in serum exosomes of NSCLC patients with brain metastases before treatment and the correlation between miR-21, miR-330 and serum tumor markers were analyzed by Pearson method. Using brain metastases identified by CT, contrast-enhanced magnetic resonance imaging of the head or surgical pathology as the gold standard, the receiver operating characteristic (ROC) curves were drawn to determine the occurrence of brain metastases in NSCLC patients based on the levels of miR-21, miR-330 and their combination in the serum exosomes before treatment. NSCLC patients were divided into the poor prognosis group and the good prognosis group according to whether or not they died of tumor during the follow-up period, and the clinical characteristics and levels of miR-21 and miR-330 in serum exosomes before treatment were compared between the two groups. The independent influencing factors of death due to tumor in NSCLC patients were analyzed by multivariate logistic regression.Results:Among 125 NSCLC patients, 68 (54.4%) were male and 57 (45.6%) were female; the age was (63±5) years old, ranging from 49 to 82 years old; 89 patients (71.2%) were adenocarcinoma and 36 patients (28.8%) were squamous cell carcinoma. The transcriptional level relative expression of miR-21 in serum exosomes of healthy control group, benign group, non-metastatic group and metastatic group increased sequentially, the transcriptional level relative expression of miR-330 decreased sequentially, the protein concentrations of NSE, CEA and SCCA increased sequentially, and the differences between each two groups were statistically significant (all P<0.001). Pearson correlation analysis showed that in the serum exosomes of NSCLC patients with brain metastases before treatment, miR-21 was positively correlated with serum NSE, CEA and SCCA levels ( r values were 0.641, 0.785 and 0.612, respectively; P values were 0.015, 0.011 and 0.019, respectively), miR-330 in the serum exosomes before treatment was negatively correlated with serum NSE, CEA, and SCCA levels ( r values were -0.612, -0.689 and -0.587, respectively; P values were 0.016, 0.021 and 0.013, respectively), and miR-21 was positively correlated with miR-330 in the serum exosomes before treatment ( r = -0.529, P = 0.023). ROC curve analysis showed that the area under the curve of miR-21, miR-330 and their combination in serum exosomes before treatment for determining the occurrence of brain metastases in NSCLC patients were 0.861 (95% CI: 0.792-0.931), 0.894 (95% CI: 0.840-0.947) and 0.906 (95% CI: 0.849-0.963), and the differences were statistically significant (all P < 0.001). The optimal cut-off value of miR-21 relative expression was 1.625, and the corresponding sensitivity and specificity were 77.4% and 71.5%, respectively; the optimal cut-off value of miR-330 was 0.611, and the corresponding sensitivity and specificity were 81.1% and 74.9%, respectively; the sensitivity and specificity when the two were combined to reach the optimal cut-off value were 84.5% and 73.8%, respectively. NSCLC patients were followed up for a median time of 19 months (95% CI: 17-21 months), and 23 cases (18.4%) died due to the tumor during the follow-up period. The proportions of patients with age ≥60 years old, clinical stage Ⅲ-Ⅳ and brain metastases and the relative expression of miR-21 in serum exosomes before treatment in the poor prognosis group were higher than those in the good prognosis group, the relative expression of miR-330 in the serum exosomes before treatment was lower than that in the good prognosis group, and the differences were all statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that the high age (≥60 years old vs. <60 years old, OR = 3.750, 95% CI: 1.191-11.806, P = 0.024), late clinical stage (stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ, OR = 4.667, 95% CI: 1.303-16.716, P = 0.018), brain metastasis (with metastasis vs. non-metastasis, OR = 2.573, 95% CI: 1.008-6.611, P = 0.049), and elevated relative expression of miR-21 in serum exosomes before treatment ( OR = 2.585, 95% CI: 1.198-6.152, P = 0.008) were the independent risk factors for death due to tumor in NSCLC patients, and elevated relative expression of miR-330 in serum exosomes before treatment was an independent protective factor for death due to tumor ( OR = 0.821, 95% CI: 0.715-0.954, P < 0.001). Conclusions:miR-21 level is high and miR-330 level is low in serum exosomes of NSCLC patients with brain metastases before treatment, and there is a negative correlation between them, and they are closely related to various serum tumor markers of NSCLC patients with brain metastases and NSCLC patients' prognosis; the combination of the two may predict the occurrence status of brain metastases in NSCLC.

Objectives:To systematically evaluate the risk factors associated with postoperative epidural hematoma in patients undergoing cervical spinal surgery.Methods:PubMed,Embase,the Cochrane Library,Web of Science,CNKI,Wanfang databases,VIP databases and CBM were searched by computer for retro-spective or prospective studies on epidural hematoma in patients undergoing cervical spine surgery published since the inception of the databases to April 2023.Two reviewers screened the literatures according to the inclusion and exclusion criteria,and NOS scale was used to evaluate the quality of the literature included.The basic information of the study,including age,gender and body mass index(BMI),as well as the factors related to the occurrence of epidural hematoma after cervical spine surgery,such as surgical segment,whether combined with posterior longitudinal ligament ossification,operative time,diabetes,hypertension,smoking,use of non-steroidal anti-inflammatory drugs and laboratory related indicators were extracted.The risk of bias analysis of the included studies was performed using funnel plots,and meta-analysis was performed using RevMan 5.4 software.Results:A total of 12 literatures were included,and the NOS quality scores of the in-cluded literatures were all 6-8 points,of which,11 were of high quality and 1 was of medium quality.Meta-analysis showed that male[odds ratio(OR)=2.84,95％confidence interval(CI)(1.73,4.67),P＜0.0001],BMI＞24kg/m2[OR=8.50,95％CI(2.56,25.24),P=0.0005],multiple surgical segments(≥2)[OR=2.26,95％CI(1.42,3.594),P=0.0005],operative time＞2h[OR=1.46,95％CI(1.08,1.97),P=0.01],preoperative administration of non-steroidal anti-inflammatory drugs[OR=3.60,95％CI(1.00,12.99),P=0.05]were the risk factors for epidural hematoma after cervical spine surgery.The results of the funnel plot were used to test the publication bias of the surgical segment and intraoperative blood loss,which were the most influential factors in the literature,and the results showed that there was no publication bias in the surgical segment,while there was partial publication bias in the intraoperative blood loss.Conclusions:Male,BMI＞24kg/m2,multi-segment surgery(sur-gical segment ≥2),operative time＞2h,and preoperative administration of nonsteroidal anti-inflammatory drugs are the risk factors for SEH after cervical spine surgery.

Objective:By analyzing the clinical data of patients with primary duodenal adenocarcinoma (PDA), the risk factors affecting the postoperative prognosis of PDA patients were discussed.Methods:The clinical data of 191 patients diagnosed with PDA in Peking University First Hospital from Jan 2009 to Dec 2022 were collected. The survival rate was calculated and the survival curve was plotted by Kaplan-Meier method. Univariate analysis was performed by Log-Rank test, and multivariate analysis was performed by COX proportional hazards regression model to obtain independent risk factors.Results:The median age of onset in patients with PDA is 65 years old, and the most common symptoms are abdominal pain and abdominal distension. Prognostic analysis showed that the survival rates at 1, 3 and 5 years were 73.8%, 44.6%, and 23.0%. The analysis of Cox risk proportional regression model showed that preoperative CA19-9 level, depth of tumor invasion, degree of differentiation, TNM stage, and surgical mode were independent risk factors for the prognosis of PDA (all P<0.01). Conclusion:The overall incidence of PDA is low, but the prognosis is rather poor. Multvariable factors are associated with its prognosis and surgery is still the mainstay for hope of cure.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Animals ; Rabbits ; Atrial Fibrillation/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; NF-E2-Related Factor 2/pharmacology* ; Molecular Docking Simulation ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism* ; Inflammation/metabolism* ; Heme Oxygenase-1