The regulatory mechanism of physiological sleep-wake / 中国药理学通报

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

Rudimentary horn pregnancy: clinical analysis of 12 cases and literature review / 中华妇产科杂志

Objective: To investigate the clinical characteristics, treatments and fertility recovery of rudimentary horn pregnancy (RHP). Methods: The clinical data of 12 cases with RHP diagnosed and treated in Peking University Third Hospital from January 1, 2010 to December 31, 2022 were retrospectively analyzed. Clinical informations, diagnosis and treatments of RHP and the pregnancy status after surgery were analyzed. Results: The median age of 12 RHP patients was 29 years (range: 24-37 years). Eight cases of pregnancy in residual horn of uterus occurred in type Ⅰ residual horn of uterus, 4 cases occurred in type Ⅱ residual horn of uterus; among which 5 cases were misdiagnosed by ultrasound before surgery. All patients underwent excision of residual horn of uterus and affected salpingectomy. After surgery, 9 patients expected future pregnancy, and 3 cases of natural pregnancy, 2 cases of successful pregnancy through assisted reproductive technology. Four pregnancies resulted in live birth with cesarean section, and 1 case resulted in spontaneous abortion during the first trimester of pregnancy. No uterine rupture or ectopic pregnancy occurred in subsequent pregnancies. Conclusions: Ultrasonography could aid early diagnosis of RHP while misdiagnosis occurred in certain cases. Thus, a comprehensive judgment and decision ought to be made based on medical history, physical examination and assisted examination. Surgical exploration is necessary for diagnosis and treatment of RHP. For infertile patients, assisted reproductive technology should be applied when necessary. Caution to prevent the occurrence of pregnancy complications such as uterine rupture, and application of cesarean section to terminate pregnancy are recommended.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine： Threatened Abortion / 中国实验方剂学杂志

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Synthesis and antibacterial activity evaluation of octapeptin derivatives / 药学学报

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

Right-to-Left Displacement of an Airgun Lead Bullet after Transorbital Entry into the Skull Complicated by Posttraumatic Epilepsy : A Case Report

Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.

Efficacy of hepatic arterial infusion chemotherapy and its multimodality therapeutic regimens in treatment of patients with advanced hepatocellular carcinoma and related prognostic factors / 临床肝胆病杂志

Objective To investigate the efficacy of continuous hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen and its multimodality therapeutic regimen in the treatment of patients with advanced hepatocellular carcinoma, as well as the influencing factors for prognosis. Methods A retrospective analysis was performed for the clinical data of 66 patients with advanced hepatocellular carcinoma who received continuous HAIC with FOLFOX regimen in Nanfang Hospital, Southern Medical University, from September 2018 to November 2021. The patients were observed in terms of objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) after treatment, and treatment-related adverse reactions were recorded. For the patients with portal vein tumor thrombus, the effect of the treatment on portal vein tumor thrombus was assessed. The Kaplan-Meier method was used for survival analysis, and the Cox regression analysis was used to investigate the influencing factors for prognosis. Results According to the RECIST1.1 criteria, FOLFOX-HAIC and its multimodality therapeutic regimen achieved an ORR of 33.3% (22/66) and a DCR of 86.4% (57/66) in the treatment of 66 patients with advanced hepatocellular carcinoma, with an mPFS time of 8.2 months and an mOS time of 22.1 months. Among the 39 patients with portal vein tumor thrombus, 2 achieved complete remission, 8 achieved partial remission, 24 achieved stable disease, and 5 had disease progression, with an ORR of 25.6% (10/39) and a DCR of 87.2% (34/39). The main adverse reactions included gastrointestinal reactions (16.7%, 11/66), pyrexia (12.1%, 8/66), liver area pain (10.6%, 7/66), bone marrow suppression (3.0%, 2/66), and contrast agent allergy (3.0%, 2/66), and there were no grade > Ⅳ toxic or side effects or deaths caused by such complications. The Cox regression analysis showed that extrahepatic metastasis (hazard ratio [ HR ]=2.668, 95% confidence interval [ CI ]: 1.357-5.245, P < 0.05) and prothrombin time (PT) ( HR =1.282, 95% CI : 1.080-1.630, P < 0.05) were independent risk factors for PFS, and aspartate aminotransferase level ( HR =1.008, 95% CI : 1.002-1.013, P < 0.05) and PT ( HR =1.303, 95% CI : 1.046-1.630, P < 0.05) were independent risk factors for OS. Conclusion FOLFOX-HAIC and its multimodality therapeutic regimen has a certain clinical effect with controllable adverse reactions in the treatment of advanced hepatocellular carcinoma.

Effect and mechanism of gerbeloid J from Gerbera piloselloides (L.) Cass. on cycle and apoptosis of breast cancer cells / 药学学报

Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.

UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood / 中国中药杂志

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Cholesterol paradox in the community-living old adults: is higher better? / 老年心脏病学杂志（英文版）

OBJECTIVE@#To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.@*METHODS@#A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators.@*RESULTS@#A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death.@*CONCLUSIONS@#In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Effect and mechanism of Puerariae Lobatae Radix in alleviating insulin resistance in T2DM db/db mice based on intestinal flora / 中国中药杂志

This study aimed to examine the effect and underlying mechanism of Puerariae Lobatae Radix on insulin resistance in db/db mice with type 2 diabetes mellitus(T2DM) based on the analysis of intestinal flora. Fifty db/db mice were randomly divided into a model group(M group), a metformin group(YX group), a high-dose Puerariae Lobatae Radix group(YGG group), a medium-dose Puerariae Lobatae Radix group(YGZ group), and a low-dose Puerariae Lobatae Radix group(YGD group). Another 10 db/m mice were assigned to the normal group(K group). After continuous administration for eight weeks, body weight and blood sugar of mice were measured. Enzyme linked immunosorbent assay(ELISA) was used to detect glycosylated serum protein(GSP) and fasting serum insulin(FINS), and insulin resistance index(HOMA-IR) was calculated. The histopathological changes in the pancreas were observed by HE staining. Tumor necrosis factor(TNF)-α expression in the pancreas was detected using immunohistochemistry. The structural changes in fecal intestinal flora in the K, M, and YGZ groups were detected by 16S rRNA. Western blot was used to detect the expression of farnesoid X receptor(FXR) and takeda G protein-coupled receptor 5(TGR5) in the ileum, cholesterol 7α-hydroxylase(CYP7A1) and sterol 27α-hydroxylase(CYP27A1) in the liver, and G protein-coupled receptors 41(GPR41) and 43(GPR43) in the colon. Compared with the K group, the M group showed increased body weight, blood sugar, serum GSP, fasting blood glucose(FBG), and FINS, increased HOMA-IR, inflammatory infiltration of islet cells, necrosis and degeneration of massive acinar cells, unclear boundary between islet cells and acinar cells, disturbed intestinal flora, and down-regulated FXR, TGR5, CYP7A1, CYP27A1, GPR41, and GPR43. Compared with the M group, the YX, YGG, YGZ, and YGD groups showed decreased body weight, blood sugar, serum GSP, FBG, and FINS, islet cells with intact and clumpy morphology and clear boundary, necrosis of a few acinar cells, and more visible islet cells. The intestinal flora in the YGZ group changed from phylum to genus levels, and the relative abundance of intestinal flora affecting the metabolites of intestinal flora increased. The protein expression of FXR, TGR5, CYP7A1, CYP27A1, GPR41, and GPR43 increased. The results show that Puerariae Lobatae Radix can improve the inflammatory damage of pancreatic islet cells and reduce insulin resistance in db/db mice with T2DM. The mechanism of action may be related to the increase in the abundance of Actinobacteria, Bifidobacterium, and Bacteroides in the intestinal tract and the protein expression related to metabolites of intestinal flora.

Epidemiological characteristics and risk factors of bronchiectasis in patients with chronic obstructive pulmonary disease in Suining area / 公共卫生与预防医学

Objective To analyze the epidemiological characteristics and risk factors of bronchiectasis in patients with chronic obstructive pulmonary disease (COPD) in Suining area, and to provide theoretical basis for COPD prevention and treatment of bronchiectasis. Methods A total of 582 patients with ACUTE exacerbation of COPD (AECOPD) admitted to grade A Hospitals in Suining area from 2019 to 2020 were selected as the investigation objects. According to whether the patients had bronchiectasis, they were divided into control group (without bronchiectasis, n=485) and observation group (with bronchiectasis, n=97). The risk factors of bronchiectasis in COPD patients were analyzed by univariate analysis and logistic regression. The clinical data of the two groups were compared, including age, sex, whether there were other diseases, respiratory tract infection, proportion of purpuric sputum, colonization rate of Pseudomonas aeruginosa. Results Of 16.84% (49/291) AECOPD patients occurred Bronchiectasis. The colonization rate of Pseudomonas aeruginosa in observation group was significantly higher than that in control group (P<0.05). The values of FVC and FEV1/FVC in observation group were significantly lower than those in control group (P<0.05). The levels of serum CRP and PCT in the observation group were significantly higher than those in the control group (P<0.05). Male (OR=2.515), high proportion of GOLD grade III/IV (OR=3.654), smoking (OR=3.472), diabetes (OR=3.829) and bacterial infection (OR=4.159) were independent risk factors for bronchiectasis in COPD patients (P<0.05). Conclusion COPD patients in Suining area have a high risk of bronchiectasis.The lung function was declined significantly.It has a high colonization rate of Pseudomonas aeruginosa. Patients who are male, have a high proportion of GOLD class III/IV, smoke, have diabetes, and have bacterial infections should be given interventions that can reduce the risk of bronchiectasis in COPD patients.

Photoelectric therapy for rosacea / 中华皮肤科杂志

Rosacea is a chronic inflammatory dermatosis mostly occurring on the central face, and its pathogenesis is still unclear. Currently, drug treatment is the first-line therapy for rosacea. In recent years, photoelectric therapy has showed a favorable therapeutic effect on rosacea by selective photothermolysis. This review summarizes latest advances in photoelectric therapy for rosacea.

A case of mitochondrial diabetes mellitus complicated with hypopituitarism and literature review / 中华内分泌代谢杂志

The clinical data of a patient with mitochondrial diabetes mellitus complicated with hypopituitarism were analyzed, the patient′s mitochondrial gene was detected by microarray capture high-throughput sequencing, and the related domestic and foreign literature was reviewed and analyzed. The results showed that the patient had m. 3243 A>G variant on MT-TL1 gene and the clinical features were consistent with mitochondrial diabetes mellitus and hypopituitarism.

Relationship between ALDH2 rs671 gene polymorphism and body fat content in Han population / 中华健康管理学杂志

Objective:To investigate the relationship between ALDH2 rs671 gene polymorphism and body fat content in Chinese Han population.Methods:It was a cross-sectional study. A total of 3 943 Chinese Han people were selected for physical examination in the Department of Health Medicine in the Second Medical Center of Chinese PLA General Hospital from January 2017 to January 2020, including 2 749 males and 1 194 females; the average age was (48.12±7.98) years. The research subjects were divided into obesity group and non-obesity group according to their body fat rate. The basic information including age, gender, disease history, height, weight, body fat content and blood samples were collected; the ALDH2 rs671 gene polymorphism was detected. Genotype and allele frequencies were compared between groups by using χ2 test. The comparison of clinical data between different genotypes was conducted by using one-way analysis of variance. The correlation between various indicators, lifestyle and genotype was analyzed by using a logistic regression model. Results:The distribution of ALDH2 rs671 genotype was wild genotype GG (68.6%), heterozygous mutant genotype GL (28.7%) and homozygous mutant genotype LL (2.7%). In terms of baseline characteristics, there were significant differences in male (67.5% vs 71.3%), body mass index (BMI, (23.12±2.64) kg/m 2 vs (27.10±2.75) kg/m 2), genotype distribution (GG 65.6% vs 70.6%), drinking history (64.4% vs 68.8%), history of hypertension (18.7% vs 36.9%), coronary heart disease (3.7% vs 5.6%) and diabetes (9.7% vs 15.0%) between the obesity and non-obesity group (all P<0.05). Multifactor logistic regression showed that ALDH2-GG genotype ( OR=1.386, 95% CI: 1.078-1.782), age ( OR=1.051, 95% CI: 1.035-1.068), and BMI ( OR=2.182, 95% CI: 2.043-2.331) were risk factors for obesity differentiated by body fat percentage, and male ( OR=0.175, 95% CI: 0.123-0.250) was protective factor (all, P<0.05). Conclusion:ALDH2 rs671 polymorphism is related to body fat content. The risk of excessive body fat content in individuals with GG genotype is significantly increased.

Correlation between serum non-high density lipoprotein cholesterol and bone mass levels in different body parts in physical examination population / 中华健康管理学杂志

Objective:To compare the relationship between non-high-density lipoprotein cholesterol (non-HDL-C) and bone mass in different body parts in the physical examination population.Methods:It was a cross-sectional study. The data of 595 physical examiners who visited the Institute of Health Management, PLA General Hospital from June to September 2016 were retrospectively analyzed. The bone mass levels of lumbar 1-4 vertebral body (spine) and femur, average bone density were measured by double light energy X-ray bone density instrument. The basic information and biochemical indices of the physical examiners were collected. The difference between blood lipid components (including Non-HDL-C) and bone mass level of each body part were analyzed.Results:According to blood lipid stratification, there were significant differences in spine T value (T-spine) between triglyceride (TG) groups (-0.15±1.41 vs -0.38±1.3), Non-HDL-C groups (-1.01±0.74 vs -1.21±0.59, -1.04±0.73 vs -1.30±0.45,-1.07±0.71 vs -1.30±0.26) and low-density lipoprotein cholesterol (LDL-C) groups (-1.01±0.71 vs -1.32±0.56)(all P<0.05). There was no statistically significant difference in other lipid groups and femoral T values in each component′s blood lipids. The T-spine decreased significantly in the LDL-C≥3.4 mmol/L group, and the differences were all significant among the Non-HDL-C group (all P<0.05). In binary logistic regression analysis, LDL-C≥3.4 mmol/L ( OR=3.961,95% CI:1.310-11.974) and Non-HDL-C>4.1 mmol/L ( OR=3.600,95% CI:1.035-12.524) were risk factors for vertebral bone mass loss (both P<0.05). Conclusion:People with elevated serum TG, Non-HDL-C and LDL-C in the physical examination population are prone to bone abnormalities. Non-HDL-C≥4.1 mmol/L and LDL-C≥3.4 mmol/L are more closely related to the vertebral bone mass loss and are the risk factors for vertebral bone mass loss.

Discussion on application of control level of radioactive contamination on personnel′s body surface in a nuclear and radiological emergency / 中华放射医学与防护杂志

There are differences and inconsistencies to some degree in the radioactive contamination control level of personnel′s body surface availiable in many national standards, thus puzzling the users. Therefore, it is proposed to compare the applicable scope, conditions and differences between relevant national standards, and combine with similar clinical nuclear medicine standards of radiological protection content to presevent recommendations on the contamination control level that should be correctly applied in an event of nuclear and radiological emergency. Based on the discussion of similar standards, the contaminated personnel with α of 0.04-10 Bq/cm 2 and β of 0.4-100 Bq/cm 2 are advised to be treated in the institutions with higher than secondary medical insititution. Both α econtamination control levels less than 0.04 Bq/cm 2 and β levels less than 0.4 Bq/cm 2 could be achivable, if fully decontaminated.

Gut microbiota profiles in the perioperative period and long-term postoperative period in children with ventricular septal defect treated with cardiopulmonary bypass / 中华实用儿科临床杂志

Objective:To explore the characteristics of gut microbiota in the preoperative, short-term postoperative and long-term postoperative period at (15.61±4.51) months in children with ventricular septal defect (VSD) of congenital heart disease (CHD) treated with cardiopulmonary bypass (CPB).Methods:A prospective study was conducted.In Guangzhou Women and Children′s Medical Center, 13 patients with VSD who were scheduled for CPB and additional 10 age- and gender-matched healthy infants as pre-CPB control group from January 2021 to January 2022 were enrolled.Fecal samples were collected at pre- and early post-CPB.Meanwhile, 18 gender- and CHD diagnosis and operation-matched patients at (15.61±4.51) months after CPB and 8 healthy age- and gender-matched children as long-term control group after CPB were also enrolled, and fecal samples were collected.16S rRNA sequencing of fecal samples from all subjects were performed and comparing the differences in gut microbiota between two groups via comparing alpha and beta diversity, parameter test or nonparametric test, and LEfSe analysis.Results:Compared with those of pre-CPB control group, there was a significant difference in the composition of gut microbiota in the preoperative period of VSD children, with significantly increased abundances of Enterobacteriaceae and Shigella, and decreased abundance of Bifidobacterium (all P<0.05). The diversity of gut microbiota was comparable in VSD children before CPB and in the short period time after CPB (all P>0.05), except for the abundances of Clostridium and Streptococcus (all P<0.05), and there was no significant difference in the relative abundances of other highly abundant gut bacteria between the two periods (all P>0.05). Compared with that in VSD children in the short period time after CPB, the abundances of short-chain fatty acids-producing microbes were significantly higher at (15.61±4.51) months postoperatively (all P<0.05), and the gut bacteria profile was similar to that of the long-term control group after CPB (all P>0.05). Conclusions:Gut microbiota imbalance exists in VSD children before CPB.The gut microbiota profile is not influenced by CPB, which returns normal at (15.61±4.51) months postoperatively.

Clinical efficacy of Compound Kushen Injection combined with SOX regimen in the treatment of elderly patients with advanced gastric cancer / 国际肿瘤学杂志

Objective:To explore the clinical efficacy and influence on quality of life of Compound Kunshen Injection combined with SOX regimen (Tigio + Oxaliplatin) in the treatment of elderly patients with advanced gastric cancer.Methods:A total of 76 elderly patients with advanced gastric cancer admitted to Caidian District People's Hospital of Wuhan from May 2017 to December 2021 were retrospectively analyzed. Patients were divided into study group ( n=38) and control group ( n=38) according to different treatment methods. The study group was treated with Compound Kunshen Injection combined with SOX regimen, and the control group was treated with SOX regimen. All patients received at least 2 cycles of chemotherapy. The disease control rate (DCR) , the changes of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) before and after treatment of the two groups were compared. The occurrence of adverse reactions to chemotherapy and the improvement of quality of life related indicators before and after treatment were observed in the two groups. Results:The DCR of the study group was 84.2% (32/38) and that of the control group was 63.2% (24/38) , with a statistically significant difference ( χ2=4.34, P=0.037) . After treatment, CEA levels in both study group and control group were decreased compared with those before treatment [7.92 (5.00, 50.23) ng/ml vs. 40.08 (6.37, 68.18) ng/ml, Z=3.53, P<0.001; 40.24 (20.12, 53.69) ng/ml vs. 41.32 (11.50, 63.90) ng/ml, Z=2.06, P=0.044], and CEA level in the study group was decreased more significantly than that in the control group ( Z=1.99, P=0.048) . After treatment, CA199 levels in both study group and control group were decreased compared with those before treatment [20.23 (17.34, 71.31) U/ml vs. 70.14 (12.75, 96.95) U/ml, Z=2.70, P=0.007; 54.25 (30.54, 76.75) U/ml vs. 62.28 (23.00, 84.80) U/ml, Z=2.37, P=0.018], with no statistically significant difference in the reduction level of CA199 between the two groups ( Z=0.73, P=0.463) . Most of the adverse reactions in the two groups during chemotherapy were grade 1-2, which disappeared after symptomatic treatment. Compared with the control group, the study group had lower incidence of gastrointestinal reaction [26.3% (10/38) vs. 52.6% (20/38) , χ2=5.50, P=0.019], myelosuppression [18.4% (7/38) vs. 44.7% (17/38) , χ2=6.09, P=0.014] and peripheral neurotoxicity [21.1% (8/38) vs. 44.7% (17/38) , χ2=4.83, P=0.028]. The improvements of QOL score [78.9% (30/38) vs. 55.3% (21/38) , χ2=4.83, P=0.028], Karnofsky performance status score [71.1% (27/38) vs. 47.4% (18/38) , χ2=4.41, P=0.036], hemoglobin [73.7% (28/38) vs. 50.0% (19/38) , χ2=4.52, P=0.034] and pain control [65.8% (25/38) vs. 24.1% (16/38) , χ2=4.29, P=0.038] of the study group were better than those of the control group, with statistically significant differences. Conclusion:Compound Kunshen Injection combined with SOX regimen in the treatment of elderly patients with advanced gastric cancer can not only improve the DCR of patients, but also reduce the serum levels of tumor markers CEA and CA199, among which the CEA decline is more obvious, reduce the incidence of adverse reactions of chemotherapy and improve the quality of life of patients.

Anthraquinone modifier KA-4c triggers endoplasmic reticulum stress and targets ATF6 against breast cancer cells / 中国药理学通报

Aim To explore the mechanism of the effect of anthraquinone modifier KA-4c on breast cancer cells, and determine its action target by drug affinity reaction target stability technique (DARTS). Methods The cell viability was detected by MTT method. The effect of KA-4c on the morphology of breast cancer cells was studied by HE staining, ER-Tracker Red and electron microscope. The apoptosis rate of breast cancer cells induced by KA-4c was detected by flow cytometry. The expression of apoptotic protein was detected by Western blotting. DARTS and CETSA were used to determine the target of KA-4c. Results KA-4c had the most significant inhibitory effect on the proliferation of triple negative breast cancer MDA-MB231 cells, and could cause endoplasmic reticulum and mitochondrial vacuolation to damage the cells. The apoptosis rate and the expression of apoptosis-related proteins CHOP and caspase-7 increased with the increase of KA-4c concentration. DARTS results showed that KA-4c could activate endoplasmic reticulum protein processing signaling pathway, in which KA-4c bound to ATF6 protein and was resistant to protease hydrolysis. The results of CETSA experiments showed that KA-4c could enhance the expression of ATF6 protein in a concentration-dependent manner. Conclusions KA-4 triggers endoplasmic reticulum stress to induce apoptosis in breast cancer cells. ATF6 may be one of the targets of KA-4c.

Effect of a novel phosphodiesterase type 5 inhibitor,CPD1,on unilateral renal interstitial fibrosis caused by ureteric obstruction in mice / 中国药理学通报

Aim To investigate the effects of CPD1,a novel phosphodiesterase 5 inhibitor,on renal pathological phenotype and fibrotic protein expression in renal fibrosis model mice. Methods Male C57BL/6 J mice were divided into three groups randomly(sham group,UUO group and UUO+CPD1 group). Unilateral ureteric obstruction model was constructed by surgery,and CPD1(5 mg·kg-1·d-1)was administered by intragastric administration two hours after the modeling for seven days. HE and Sirius Red staining were used to observe the distribution of tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of fibronectin(FN),α-SMA,collagen-I and kidney injury molecule-1(Kim-1). Results Compared with sham operation group,the renal tubules of mice were dilated and accompanied by a large amount of inflammatory infiltration. Moreover,the expressions of FN,α-SMA,collagen-I and Kim-1 proteins increased significantly(P<0.05)in UUO group. CPD1 treatment improved the kidney structure and decreased the expression of collagen fibers. Furthermore,CPD1 inhibited the expression of FN,α-SMA,collagen-I and Kim-1 markedly(P<0.05). Conclusions Phosphodiesterase 5 inhibitor CPD1 alleviates the progression of renal fibrosis induced by unilateral ureteral obstruction through down-regulating ECM deposition in the extracellular matrix and expression of Kim-1. The specific mechanism remains to be further studied.