Effect and mechanism of Dahuang Zhechong Pills in improving liver aging in rats by regulating ROS-mediated PI3K/Akt/FoxO4 signaling pathway / 中国中药杂志

Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.

Effects and mechanisms of total flavones of Abelmoschus manihot in attenuating diabetic tubulopathy by targeting endoplasmic reticulum stress-induced cell apoptosis / 中国中药杂志

Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.

Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway / 中国中药杂志

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.

Association between HLA-DRB1 gene polymorphisms and genetic susceptibility of early-onset severe preeclampsia / 中国当代儿科杂志

OBJECTIVES@#To explore the correlation between the single nucleotide polymorphisms (SNP) of rs3135388, rs114293611 and rs142804168 of HLA-DRB1 gene and early-onset severe preeclampsia (sPE).@*METHODS@#Blood samples were collected from 102 early-onset sPE mothers and their neonates (sPE group), as well as 120 normotensive mothers and their neonates (control group). Sanger sequencing was performed to compare the genotype distribution, allele frequencies, and differences in genotype distribution after maternal-infant compatibility between the two groups.@*RESULTS@#Statistically significant differences in genotype distribution at rs114293611 of HLA-DRB1 gene were observed between sPE and control groups in both mothers and neonates (P<0.05). The frequency of the T allele at rs114293611 was higher in the sPE group of neonates than that in the control group (P<0.05), while no significant difference was found between the two groups of mothers (P>0.05). The maternal-infant genotype compatibility analysis showed significant differences in genotype distribution between sPE and control groups (P<0.05). There were no significant differences in genotype distribution and allele frequencies at rs3135388 and rs142804168 of HLA-DRB1 gene between the two groups of mothers and neonates (P>0.05).@*CONCLUSIONS@#The SNP at rs114293611 of HLA-DRB1 gene may be associated with the development of early-onset sPE in mothers. Maternal-infant genotype compatibility abnormality at rs114293611 of HLA-DRB1 gene may be a predisposition factor for the development of sPE.

A phased swallowing training program after partial laryngectomy / 中华物理医学与康复杂志

Objective:To construct an evidence-based phased swallowing training program for patients after partial laryngectomy applying the Delphi method.Methods:Evidence was screened systematically applying evidence-basing principles to construct a first draft of a phased swallowing training program for patients after partial laryngectomy. After two rounds of Delphi expert consultation a final draft was formed.Results:The protocol was composed of 27 items covering 5 aspects of the gastrointestinal decompression period, the first- and second-stage continuous tube feeding periods, trial feeding of the intermittent tube feeding period and the oral feeding stage.Conclusion:The phased swallowing training program is scientifically sound and feasible in clinical practice. It can provide references for clinic staff to improve swallowing management.

Effects and mechanisms of total flavones of Abelmoschus manihot in inhibiting podocyte necroptosis and renal fibrosis in diabetic kidney disease / 中国中药杂志

Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-β1(TGF-β1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.

Effect of Lulong Zaisheng Decoction II on chemotherapy-induced bone marrow suppression and its mechanism / 中国药理学通报

Aim To investigate the effect of Lulong Zaisheng Decoction II on chemotherapy-induced bone marrow suppression in nude mice bearing colorectal cancer. Methods Male BALB/C nude mice were inoculated with human colon cancer cell HT-29 under the armpit. The tumor bearing nude mice were randomly divided into five groups: control group, chemotherapy group, positive drug group, Lulong Zaisheng Decoction II groups with high and low doses. The mice were given drugs by gavage once a day for 10 consecutive days. From the fourth day of the experiment, except for the control group, the nude mice were intraperitoneally injected with 5-FU at dose of 25 mg • kg

Research Progress of Clonal Hematopoiesis of Indeterminate Potential in Multiple Myeloma --Review / 中国实验血液学杂志

With the progress of medical technology, cloning hematopoietic was found to be widely exist in normal people. Because of its clinical significance and prognosis is unclear, it is named clonal hematopoiesis of indeterminate potential(CHIP), which has been detected in blood diseases such as myelodysplastic syndrome and lymphoma, and proven to be related to poor prognosis. Recently, CHIP has been also detected in patients with multiple myeloma (MM). In this article, the definition and influencing factors of CHIP, clinical significance, prognosis and treatment in MM were reviewed.

Study on factors in patients to get rid of blindness with post traumatic infectious endophthalmitis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the factors affecting patients with post traumatic infectious endophthalmitis(PTIE)relieving from blindness.METHODS: A retrospective study was conducted on 169 patients(169 eyes)with PTIE from January 2010 to December 2020 in the department of ophthalmology, the Affiliated Hospital of Nantong University. After treatment of intravitreal injection of antibiotics(IVIA)and/or pars plana vitrectomy(PPV), the patients were divided into the getting rid of blindness group(103 eyes)and unilateral blindness group(66 eyes)according to the last follow-up of best correct visual acuity(BCVA)≥0.05. The factors affecting the patients to get rid of blindness were analyzed.RESULTS: The rate of relieving from blindness was 53.5%. Univariate analysis showed that BCVA before treatment ≥ hand movement, no retinal detachment, fundus grade of endophthalmitis < grade 3 and no strong virulence of infected microorganisms were beneficial for patients to get rid of blindness(P<0.05). Multivariate Logistic regression analysis identified that BCVA before treatment ≥ hand movement(OR=0.253, 95%CI: 0.108-0.592)and no retinal detachment(OR=0.241, 95%CI: 0.103-0.564)were favorable factors for patient to get rid of blindness.CONCLUSION: Better BCVA before treatment, no retinal detachment, endophthalmitis fundus grade < 3, and no strong virulence of infected microorganisms are favorable factors for patients with PTIE to get rid of blindness finally.

Evaluation of a China-made disposable peroral cholangioscope in an animal experiment / 中华消化内镜杂志

Objective:To evaluate the efficacy and safety of a China-made disposable peroral cholangioscope in animal cholangioscopy.Methods:Six healthy Bama minipigs underwent the domestic disposable peroral cholangioscopy after anesthesia. The operation performance and image quality of the products were evaluated, and intraoperative and postoperative complications were recorded.Results:All 6 animals received the domestic disposable peroral cholangioscopy. The cholangioscope showed good operating performance and could smoothly enter the biliary tract through the duodenoscope. The water injection, suction and instrument channels were unobstructed. The cholangioscopic image was clear, the color resolution was good, and there was no image distortion. The lumen and the mucosal surface could be accurately assessed. During the examination, there was no operative injuries such as bleeding, perforation, or adverse events such as respiratory depression or cardiac arrest. All pigs survived the operation with no adverse reaction.Conclusion:The China-made disposable peroral cholangioscope is safe, with good operability and high-quality image.

Hypoxia promotes differentiation of human induced pluripotent stem cells into embryoid bodies in vitro / 南方医科大学学报

OBJECTIVE@#To investigate effects of physiological hypoxic conditions on suspension and adherence of embryoid bodies (EBs) during differentiation of human induced pluripotent stem cells (hiPSCs) and explore the underlying mechanisms.@*METHODS@#EBs in suspension culture were divided into normoxic (21% O2) and hypoxic (5% O2) groups, and those in adherent culture were divided into normoxic, hypoxic and hypoxia + HIF-1α inhibitor (echinomycin) groups. After characterization of the pluripotency with immunofluorescence assay, the hiPSCs were digested and suspended under normoxic and hypoxic conditions for 5 days, and the formation and morphological changes of the EBs were observed microscopically; the expressions of the markers genes of the 3 germ layers in the EBs were detected. The EBs were then inoculated into petri dishes for further culture in normoxic and hypoxic conditions for another 2 days, after which the adhesion and peripheral expansion rate of the adherent EBs were observed; the changes in the expressions of HIF-1α, β-catenin and VEGFA were detected in response to hypoxic culture and echinomycin treatment.@*RESULTS@#The EBs cultured in normoxic and hypoxic conditions were all capable of differentiation into the 3 germ layers. The EBs cultured in hypoxic conditions showed reduced apoptotic debris around them with earlier appearance of cystic EBs and more uniform sizes as compared with those in normoxic culture. Hypoxic culture induced more adherent EBs than normoxic culture (P < 0.05) with also a greater outgrowth rate of the adherent EBs (P < 0.05). The EBs in hypoxic culture showed significantly up-regulated mRNA expressions of β-catenin and VEGFA (P < 0.05) and protein expressions of HIF-1 α, β-catenin and VEGFA (P < 0.05), and their protein expresisons levels were significantly lowered after treatment with echinomycin (P < 0.05).@*CONCLUSION@#Hypoxia can promote the formation and maturation of suspended EBs and enhance their adherence and post-adherent proliferation without affecting their pluripotency for differentiation into all the 3 germ layers. Our results provide preliminary evidence that activation of HIF-1α/β-catenin/VEGFA signaling pathway can enhance the differentiation potential of hiPSCs.

Risk factors for complications after endoscopic retrograde cholangiopancreatography in super-aged patients / 中华消化内镜杂志

Objective:To study the risk factors for complications after endoscopic retrograde cholangiopancreatography (ERCP) in super-aged patients (≥80 years).Methods:Clinical data of 512 super-aged patients with pancreaticobiliary diseases who underwent 638 ERCP procedures at the Digestive Endoscopy Center, Zhongnan Hospital of Wuhan University, from July 2011 to June 2021, were studied retrospectively. Indications and results of the ERCP operations were analyzed. Multivariate logistic regression model was used to analyze the risk factors for ERCP-related complications.Results:The total success rate of ERCP cannulation in super-aged patients was 94.0% (600/638), which showed no difference compared with that of patients of <60 years old (2 433/2 557, 95.2%) or patients of 60~<80 years old (2 815/3 004, 93.7%) ( χ2=5.49, P=0.064). The overall incidence of post-ERCP complications was 15.2% (97/638), and the in-hospital mortality was 2.1% (11/512), which showed significant difference compared with patients of <60 years old (8/1 809, 0.4%) and patients of 60-<80 years old (21/2 127, 1.0%) ( χ2=13.39, P=0.002). Multivariate regression analysis showed that hypertension ( HR=1.94, 95% CI: 1.237-3.041, P=0.004), history of upper gastrointestinal reconstruction ( HR=2.28, 95% CI: 1.064-4.891, P=0.034), endoscopic sphincterectomy ( HR=1.65, 95%CI: 1.012-2.679, P=0.045), early procedure period ( HR=0.57, 95% CI: 0.352-0.923, P=0.022), operation time >30 minutes ( HR=1.74, 95% CI: 1.094-2.759, P=0.019), preoperative white blood cell count >9.5×10 9/L ( HR=2.66, 95% CI: 1.661-4.257, P<0.001) and procalcitonin ≥0.05 ng/L ( HR=2.54, 95% CI: 1.172-5.513, P=0.018) were independent risk factors for post-ERCP complications. Conclusion:ERCP is safe and effective for super-aged patients. However, much attention should be paid to post-ERCP complications of patients with hypertension, history of upper gastrointestinal reconstruction, endoscopic sphincterectomy, operation time >30 minutes, preoperative white blood cell count >9.5×10 9/L and procalcitonin ≥0.05 ng/L to avoid serious adverse events such as mortality.

Three osteotomy methods and bone healing in Ilizarov tibial bone transport / 中华创伤骨科杂志

Objective:To explore the effects of 3 osteotomy methods on the bone healing in Ilizarov tibial bone transport.Methods:The data of 93 patients were retrospectively reviewed who had been treated by Ilizarov single-segment tibial bone transport at Department of Hand Surgery, The Second Hospital of Tangshan from December 2003 to April 2019. Minimally invasive osteotomy was performed in 16 patients [group A: 16 males with an age of (37.1±8.3) years; 5 cases of type Ⅱ and 11 ones of type Ⅲ by Gustilo classification], subperiosteal saw osteotomy in 57 patients [group B: 47 males and 10 females with an age of (39.1±11.8) years; 17 cases of type Ⅱ and 40 ones of type Ⅲ by Gustilo classification] and extraperiosteal wire saw osteotomy in 20 patients [group C: 19 males and one female with an age of (37.7±11.2) years; 18 cases of type Ⅱ and 2 cases of type Ⅲ by Gustilo classification]. The 3 groups were compared in terms of the bone healing index and the Association for the Study and Application of the Method of Ilizarov (ASAMI) functional scores.Results:The 3 groups were comparable because there was no significant difference in the preoperative general data between them ( P>0.05). All the patients were followed up for 19 to 50 months (average, 27.4 months). All patients achieved bony healing, and their associated complications were cured after corresponding treatments. There were no significant differences in the bone healing index between the 3 groups [(53.09±21.88) d/cm for group A, (59.97±33.29) d/cm for group B and (46.20±14.11) d/cm for group C] ( P>0.05). There were no significant differences either in the good to excellent rate by the ASAMI functional scores between the 3 groups (87.5% for group A, 89.5% for group B and 90.0% for group C) ( P> 0.05). Conclusion:All the 3 osteotomy methods may achieve good bony union, leading to similar bone healing indexes and postoperative functional scores.

Cold snare polypectomy for colorectal adenoma: a retrospective cohort study / 中华消化内镜杂志

Objective:To explore the curative effect and safety of cold snare polypectomy for colorectal adenoma of less than 15 mm.Methods:Data of 464 colorectal adenoma from 315 patients who were treated with cold snare polypectomy (CSP) and cold endoscopic mucosal resection (cold EMR) in the Third People′s Hospital of Jingdezhen from January 2018 to December 2019 were collected. Patients were divided into group A(3-5 mm), B (6-9 mm), and C (10-15 mm) according to the size of adenoma. Enbloc resection rate, immediate bleeding during polypectomy, delayed postpolypectomy bleeding, cold snare defect protrusions(CSDPs)and postoperative recurrence were analyzed.Results:The overall enbloc resection rate was 99.4%(461/464), and 100.0%(248/248), 98.8%(170/172), 97.7%(43/44) respectively in group A, B, and C without significant difference( P =0.126, 95% CI: 0.097-0.157). The overall incidence of immediate bleeding during polypectomy was 1.1%(5/464), and 0.4%(1/248), 1.7%(3/172), 2.3%(1/44) respectively in group A, B, and C without significant difference( P = 0.267, 95% CI: 0.227-0.308), showing an upward trend in the immediate postpolypectomy bleeding incidence with the increase of diameter of the polyps. No delayed postpolypectomy bleeding occurred. The overall incidence of CSDPs was 20.5%(95/464), 16.4%(63/384) and 40.0%(32/80) in the group of CSP and cold EMR respectively with significant difference( P<0.001, 95% CI: 0-0.006), showing an upward trend in the incidence of CSDPs with the increase of the diameter. A total of 286 adenomas in 195 patients were followed up. The median follow-up time was 9.7 months. Three patients relapsed. Conclusion:CSP is safe and effective for colorectal adenoma ≤15 mm with low incidence of immediate bleeding during polypectomy and recurrence, and no delayed postprocedural bleeding.

Metabolic module identification and biological mechanism of Xiaoyaosan for treatment of depression / 药学学报

The antidepressant effect of Xiaoyaosan has been demonstrated. It is of value to explore the biological mechanism of Xiaoyaosan in the treatment of depression from the perspective of functional modules by using the method of functional module division of the metabolic network. The differential metabolites and related enzymes and proteins regulated by Xiaoyaosan were identified in the database. Pathway enrichment analysis and crosstalk pathway analysis of Xiaoyaosan regulated metabolites was carried out. A network of differentially regulated metabolites and their enzymes and proteins was constructed by using the STRING tool. The CNM decomposition algorithm was used to extract the functional modules of the network and enrichment analysis of functional modules was carried out. The results show that Xiaoyaosan regulates 97 differential metabolites, 234 related enzymes and 258 depression-related proteins. The pathways crosstalk analysis was divided into two sub-networks, one of which is related to the neural system and cell signal transduction, the other is related to the endocrine system and metabolic pathways. KEGG pathway enrichment analysis of the network and 9 functional modules extracted by the CNM algorithm shows that module 1 and module 3 belong to the pathways that can be enriched into more pathways with fewer proteins. The corresponding functions of these pathways include the endocrine system, amino acid metabolism, the nervous system and signal transduction. In this study, pathway crosstalk analysis and metabolic network module division strategies were used to explain the biological mechanism of Xiaoyaosan in the treatment of depression, providing ideas and methods for in-depth study of the pharmacological mechanism of this traditional Chinese medicine from the perspective of metabolic regulation.

Value of CT radiomics for prediction of pathological response to neoadjuvant chemoradiotherapy in esophageal cancer / 中华放射肿瘤学杂志

Objective:To establish a radiomics-based biomarker for predicting pathological response after preoperative neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal cancer.Methods:From 2008 to 2018, 112 patients with locally advanced esophageal cancer who received nCRT were enrolled. All patients were treated with preoperative nCRT combined with surgery. Enhanced CT images and clinical information before nCRT were collected. A lesion volume of interest was manually delineated. In total, 670 radiomics features (including tumor intensity, shape and size, texture and wavelet characteristics) were extracted using the pyradiomics package in PYTHON. The stepwise regression combined with the best subset were employed to select the features, and finally the Logistic regression model was adopted to establish the prediction model. The performance of the classifier was evaluated by the area under the ROC curve (AUC). Results:The pathological complete remission (pCR) rate was 58.0%(65/112). 10 radiomics features were included in the final model, The most relevant radiomics feature was the gray feature (the texture information of the image), followed by the shape and voxel intensity-related features. In the training set, the AUC was 0.750 with a sensitivity of 0.711 and a specificity of 0.778, the corresponding values in the testing set were 0.870, 0.757 and 0.900, respectively.Conclusions:Models based on radiomics features from CT images can be utilized to predict the pathological response to nCRT in esophageal cancer. As it is efficient, non-invasive and economic model, it could serve as a promising tool for individualized treatment when validated by further prospective trials in the future.

Mechanisms of Classical Prescriptions and Their Active Components in Immunosenescence Regulation： A Review / 中国实验方剂学杂志

As the body ages， the immune system will undergo a series of changes， which are termed "immunosenescence" and are embodied in immune cells. Previous studies have shown that the immune cells involved in the regulation of immunosenescence include intrinsic immune cells and adaptive immune cells. Intrinsic immune cells are neutrophils， monocytes/macrophages， myeloid-derived suppressor cells， dendritic cells， natural killer cells， etc.， and the underlying mechanisms involve the regulation of cell number， phagocytosis， chemotaxis， adhesion， the function of toll-like receptor （TLR）， antigen presentation， macrophage polarization， cytotoxicity， migration， etc. The adaptive immune cells include T-lymphocytes and B-lymphocytes， and the underlying mechanisms involve the regulation of cell development， proliferation， differentiation， cell number， telomerase activity， self-reactive antibodies， etc. Immunosenescence is the manifestation of aging in the human body and is also an important target for delaying aging by Chinese medicine and western medicine. In recent years， scholars have found some classical prescriptions and their active components （such as Dushentang and total saponins in Panax ginseng leaves， and Shengmaiyin and anwulignan and total saponins in P. ginseng stems and leaves） can regulate immunosenescence by targeting the immune cells and interfering with their molecular regulatory mechanisms. In addition， the mechanisms of the classical prescriptions in regulating immunosenescence are closely related to autophagy. The representative prescription embodying the therapeutic principles of resolving blood stasis and promoting regeneration， Dahuang Zhechongwan， can delay D-galactose-induced renal aging in mice， and its underlying mechanisms are related to the regulation of the number and activity of thymic immune cells and improvement of the protein expression of autophagy-related markers and inflammatory cytokines in the kidney. Therefore， exploring the effects of the classical prescriptions and their active components by targeting the mechanisms of immunosenescence will become a new direction for investigating and developing anti-aging drugs.

Performance analysis of light initiated chemiluminescence assay in detecting anti-HCV, anti-HIV and syphilis / 中国输血杂志

【Objective】 To evaluate the performance of light initiated chemiluminescence assay in the detection of hepatitis c virus (HCV), human immunodeficiency virus (HIV) and Treponema pallidum (TP) antibodies. 【Methods】 According to Guidance on the Verification of Qualitative Measurement Procedures used in the Clinical Immunology(CNAS-GL038: 2019) and Guidance on the Verification of Quantitative Measurement Procedures used in the Clinical Chemistry(CNAS-GL037: 2019), the coincidence rate, detection limit, precision and critical value of the detection of HCV, HIV and TP antibodies by the automatic light initiated chemiluminescence assay system LICA500 were verified. 【Results】 The concordance rate of LICA500 and ELISA in HCV antibody and HIV antibody detection was 100%. In terms of syphilis antibody detection, the concordance rate with TPPA results was 95%. The detection limit test showed that the detection limits of LICA500 against HCV antibody, HIV antibody and TP antibody reached 0.04 NCU/mL, 0.5 NCU/mL and 0.25 NCU/mL, respectively, which were all higher than the manufacturer′s declared detection limits of 0.2 NCU/mL, 1 NCU/mL and 0.5 NCU/mL. The in-batch CV and total CV of LICA500 for HCV, HIV and TP antibodies were less than 10%. The C50 was verified by critical value experiment, and the positive results of HCV antibody, HIV antibody and TP antibody at the critical concentration accounted for 45%, 45% and 48%, respectively. The percentage of negative results for (critical concentration -20%) was 98%, and the percentage of positive results for (critical concentration + 20%) was 100%, indicating that the concentration range from (critical concentration -20%) to (critical concentration + 20%) was in the 95% range of this method. 【Conclusion】 The detection of HCV, HIV and TP antibodies by LICA500 has a high concordance rate with the current commonly used detection methods, suitable for rapid screening and batch examination before surgery and blood transfusion.

Interaction of smoking and being bullied on suicidal behaviors: a school-based cross-sectional survey in China

BACKGROUND@#Suicidal behaviors are seriously social issues among adolescents in the world. Exposed to smoking and being bullied are risk factors of suicidal behaviors. The present study was aimed to examine the interaction of smoking and being bullied on suicidal behaviors among Chinese adolescents.@*METHODS@#A total of 18,900 students were involved in the questionnaire study, in four cities of China from November 2017 to January 2018. Suicidal behaviors, smoking, and being bullied were measured by self-reported validated instruments. Chi-square tests and logistic regression were used to analyze the associations of suicidal ideation (SI)/suicidal plan (SP)/suicidal attempt (SA), smoking, and being bullied.@*RESULTS@#The prevalence of smoking, being bullied, SI/SP/SA, were 3.1%, 20.6%, 26.4%, 13.2%, and 5.2% respectively. Interaction analysis indicated that being bullied was associated with a greater increase in the likelihood of suicidal behaviors for adolescents with smoking than for those without smoking.@*CONCLUSIONS@#These finding suggest that smoking exacerbates the association between being bullied and suicidal behaviors. Future research should explore how and why smoking appears to more bully-victims than for those without smoking and how to mitigate it.

Effects and mechanisms of Supplemented Gegen Qinlian Decoction Formula against podocyte pyroptosis and insulin resistance in model rats with diabetic kidney disease / 中国中药杂志

This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.