Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease.

INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.

The regulation and guidance of long-term care insurance to the demands of home and community-based care:International experiences and implications / 中国卫生政策研究

In order to implement a"people-centered"service concept and promote the sustainability of long-term care systems,countries worldwide are increasingly focusing on benefit package design when allocating and using public long-term care funds.This emphasis is aimed at regulating and guiding long-term care demand and developing home and community-based care.Based on the purchasing theory,this study categorized the long-term care benefit package models in representative countries into two types:"Institutional Eligibility Restrictions Type"and"Home-care-focused Benefit Type",and further elaborated the specific benefit package design.In China,long-term care insurance are still in the initial stages of development.We should optimize the service utilization structure and promote a rational allocation of resources through purchasing,while incorporating diverse benefit designs such as eligibility restrictions,differential benefit levels,and supplementary support,to establish a robust,multi-tiered long-term care system based on home and community-based care.

Regulatory effect of physiological tensile stress on differentiation of ATDC5 chondrocytes through Nell-1/Ihh signaling pathway / 吉林大学学报(医学版)

Objective:To discuss the regulatory effect of physiological tensile stress on the differentiation of chondrocytes,and to clarify the associated signaling pathway mechanism.Methods:The ATDC5 chondrocytes were cultured in vitro and subjected to physiological tensile stress by four-point bending cell mechanical loading device.Initially,the cells were divided into control group and tensile stress group(2 000 μstrain/2 h group),and further divided into different stress magnitudes(1 000,2 000,and 3 000 μstrain)for 2 h,and 2 000 μstrain for different duration time(1,2,and 4 h)groups;the cells without tensile stress were used as control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of type Ⅱ collagen(Col-Ⅱ),type Ⅹ collagen(Col-Ⅹ),aggregated proteoglycom(Aggrecan),sex-determining region Y-box protein 9(SOX9),vascular endothelial growth factor(VEGF),proliferating cell nuclear antigen(PCNA),Nel-like molecule tyep 1(Nell-1),Runt-related transcription factor 2(Runx2),Indian hedgehog(Ihh),patched homolog 1(Ptch-1),GLI family zinc finger protein 1(Gli-1),and hedgehog interacting protein 1(Hhip-1)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1,Runx2,and Ihh proteins in the cells in various groups.The ATDC5 cells were divided into control group,cyclopamine group,tensile stress group,and cyclopamine + tensile stress group.RT-qPCR method was used to detect the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1 and Ihh proteins in the cells in various groups.Results:Compared with control group,the expression levels of Col-Ⅱ,Col-Ⅹ,Aggrecan,SOX9,VEGF,and PCNA mRNA in the cells in 2 000 μstrain/2 h group were significantly increased(P<0.01);after treated with 2 000 μstrain tensile stress for different duration time(1,2,and 4 h)or different tensile stresses(1 000,2 000,and 3 000 μstrain)for 2 h,compared with control group,the expression levels of Runx2 mRNA in the cells in other groups were increased with the prolongation of time or the increasing of tensile stress(P<0.01),and the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA were gradually increased(P<0.01),the expression levels reached the peaking at 2 000 μstrain/2 h,and then decreased but remained significantly higher than that in control group(P<0.01).The Western blotting results showed that the expression levels of Nell-1,Runx2,and Ihh proteins in the cells were consistent with the change trend of mRNA expression levels.After pre-treated with cyclopamine,compared with control group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine group were significantly decreased(P<0.01),and the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in tensile stress and cyclopamine+tensile stress groups were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine+tensile stress group were significantly increased(P<0.01);compared with tensile stress group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine + tensile stress group were significantly decreased(P<0.01).Compared with control group,the expression level of Ihh protein in the cells in cyclopamine group was significantly decreased(P<0.01),but there was no significant difference in expression level of Nell-1 protein in the cells between control group and cyclopamine group(P>0.05),while the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with tensile stress group,in the expression levels of Nell-1 and Ihh proteins in the cells in cyclopamine + tensile stress group had no significant differences(P>0.05).Conclusion:After stimulated with physiological tensile stress,Nell-1 can activate the Ihh signaling pathway upstream,and regulate the differentiation of the ATDC5 chondrocytes.

Study on the Analgesic Effect and Mechanism of Buyang Huanwu Decoction on Diabetic Peripheral Neuropathy Rats / 广州中医药大学学报

Objective To investigate the analgesic effect and mechanism of Buyang Huanwu Decoction on diabetic peripheral neuropathy(DPN)rats.Methods Sixty rats were divided into normal group,model group,low-,medium-and high-dose groups of Chinese medicine,and high-dose + H-89[protein kinase A(PKA)inhibitor]group,with 10 rats in each group.Except for the normal group,rats in all other groups were fed with high-fat and high-sugar chow combined with intraperitoneal injection of streptozotocin(STZ)method to construct DPN model.At the end of drug administration,the foot thermal pain threshold of rats was detected,the motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV)of rats was measured,the intraepidermal nerve fiber(IENF)in the epidermis was observed by immunohistochemistry,and serum fasting insulin(FINS),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),insulin resistance index(HOMA-IR),and the interleukin(IL)-1β,IL-6,tumor necrosis factor α(TNF-α),vascular endothelial growth factor(VEGF),angiopoietin 1(Ang-1),CD34 levels,cyclic adenosine monophosphate(cAMP)concentration in the sciatic nerve tissues were detected by enzyme-linked immunosorbent assay(ELISA),and Western Blot assay to detect the PKA and the carbohydrate responsive element binding(CREB)in the sciatic nerve tissues.Results Compared with the normal group,foot thermal pain threshold,TC,TG,LDL-C,HOMA-IR,IL-1β,IL-6 and TNF-α levels were significantly increased in the model group(P＜0.05),HDL-C,FINS,VEGF,Ang-1,CD34,IENF,MNCV and SNCV values,cAMP concentration levels,PKA and CREB phosphorylation levels were significantly reduced(P＜0.05).Compared with the model group,the above indexes were significantly improved in the low-,medium-and high-dose groups of Chinese medicine(P＜0.05)in a dose-dependent manner.Compared with the Chinese medicine high-dose + H-89 group,all the indexes were reversed in the Chinese medicine high-dose group.Conclusion Buyang Huanwu Decoction can improve insulin resistance and lipid metabolism,reduce limb pain,improve local microcirculation disorder,and protect nerve function in DPN rats,which reflects the therapeutic characteristics of"activating blood circulation and relieving pain".The pain-relieving effect of Buyang Huanwu Decoction may be related to the improvement of local microcirculation,inhibition of inflammatory factor release and regulation of cAMP/PKA/CREB signaling pathway protein expression.

Application value of hydrogel in image guided radiotherapy for prostate cancer / 解放军医学杂志

Objective To evaluate the application value of hydrogel in image guided radiotherapy(IGRT)for prostate cancer(PCa).Methods Eighty PCa patients in the First Affiliated Hospital of Hebei North University from October 2022 to February 2023 were collected.The patients were divided into experiment group injected with hydrogel(n=33)and control group without hydrogel(n=47)by central random system allocation.The acute and advanced radiation proctitis(RP)incidence rate of the two groups were compared.Patients in experimental group were divided into RP group(n=5)and non-RP group(n=28).The independent risk factors leading to RP were analyzed by using logistic regression for PCa patients.Results In experiment group,12.1％(4/33)of the patients developed acute grade Ⅰ RP,and 3.0％(1/33)developed advanced grade Ⅰ RP.In control group,31.9％(15/47)of the patients developed acute grade Ⅰ RP,and 12.8％(6/47)developed acute grade Ⅱ RP;19.1％(9/47)of patients developed advanced grade Ⅰ RP,4.3％(2/47)developed advanced grade Ⅱ RP,and 2.1％(1/47)developed advanced grade Ⅲ RP.The incidence of acute and advanced RP in experiment group was lower than that in control group(P<0.05).The application of hydrogel effectively reduced rectal toxicity.Age,rectal volume,V70 and V78 were independent risk factors for the incidence of RP in Pca patients(P<0.05).The characteristics of hydrogel injection were not related to the incidence of RP for Pca patients.Conclusions Hydrogel can effectively reduce the rectal toxicity for Pca patients in IGRT and has little impact on the overall treatment.Hydrogel has certain clinical application and promotion value.

Efficacy and Side Effects of Mixed-Strategy Electroconvulsive Therapy: A Proof-of-Concept Randomized Clinical Trial on Late Life Depression

Objective@#Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient’s resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects @*Methods@#This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies. @*Results@#In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004). @*Conclusion@#msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.

Vaccination in patients with inflammatory bowel disease-Asian perspectives: the results of a multinational web-based survey in the 8th Asian Organization for Crohn's and Colitis meeting.

BACKGROUND/AIMS: Long-term immunosuppressive therapies used to treat inflammatory bowel disease (IBD) are associated with an increased risk of infections, many of which can be prevented by vaccination. We assessed physicians' current approaches and clinical practices regarding vaccinations for IBD patients in different Asian countries/regions. METHODS: An internet-based survey was conducted among members of the Asian Organization for Crohn's and Colitis from September 2020 to November 2020. The questionnaire consisted of 2 parts covering general opinion on the relevance of vaccinations and clinical practice of vaccination. RESULTS: Overall, 384 Asian medical doctors responded to the survey. The majority of respondents considered it very (57.6%) or sufficiently (39.6%) important to perform vaccinations as recommended by the guidelines. About half of the Asian physicians (52.6%) were usually or always performing vaccinations. The influenza vaccine was the most frequently recommended vaccine for IBD patients. Half of the respondents (51.3%) did not recommend hepatitis A vaccine, especially in China (61.6%) and Japan (93.6%). The diphtheria, tetanus, and pertussis vaccine were never (35.2%) or rarely (29.4%) recommended. CONCLUSIONS: The findings of this survey indicated similarities among countries/regions in terms of the current approaches and practices regarding vaccination of IBD patients; however, there are some differences that might reflect each country's domestic vaccination guidelines and health insurance particularly with certain vaccines in some countries/regions. Although Asian physicians largely recommend vaccination, more awareness among doctors and Asian consensus regarding differences in IBD vaccination among countries/regions may be required.

Efficacy and Safety of Keverprazan Compared With Lansoprazole in the Treatment of Duodenal Ulcer: A Phase III, Randomized, Double-Blind, Multicenter Trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.

Use of the Scissor-Type Knife During the Peroral Endoscopy Myotomy Procedure for the Treatment of Achalasia.

Peroral endoscopic myotomy (POEM) is one of the first-line treatment modalities along with pneumatic dilation and Heller myotomy for patients with achalasia. Endoscopists, especially trainees during the learning phase, commonly face difficulty in tissue plane dissection and selective myotomy while working near the esophagogastric junction, with increased risks of inadvertent injury, unexpected bleeding, and inadequate myotomy. To minimize the technical difficulty and improve the safety of POEM, we describe a protocol for using a scissor-type knife for the main steps of POEM, including mucosal incision, submucosal tunneling, myotomy, and hemostasis. The standard techniques used with the scissor-type knife involve grasping the target tissue, and then dissection or coagulation. The confirmation of the cutting line after grasping improves the accuracy and reliability of dissection, which is particularly useful for the selective myotomy of the internal circular muscle. Meanwhile, the scissor-type knife provides enhanced hemostatic capability and enables hemostasis and pre-coagulation without the device exchange for hemostatic forceps. Evaluation of the clinical outcomes in three patients who successfully received POEM using the scissor-type knife revealed no perioperative adverse events. At the 3-month follow-up, all patients achieved clinical success with postoperative Eckardt scores ranging from 0 to 1. In conclusion, the use of a scissor-type knife could minimize the technical difficulty and improve the safety of the POEM procedures, which may be suitable for trainees during the learning phase.

An Open Dataset of Annotated Metaphase Cell Images for Chromosome Identification.

Chromosomes are a principal target of clinical cytogenetic studies. While chromosomal analysis is an integral part of prenatal care, the conventional manual identification of chromosomes in images is time-consuming and costly. This study developed a chromosome detector that uses deep learning and that achieved an accuracy of 98.88% in chromosomal identification. Specifically, we compiled and made available a large and publicly accessible database containing chromosome images and annotations for training chromosome detectors. The database contains five thousand 24 chromosome class annotations and 2,000 single chromosome annotations. This database also contains examples of chromosome variations. Our database provides a reference for researchers in this field and may help expedite the development of clinical applications.

Special issue "The advance of solid tumor research in China": Prediction of Sunitinib efficacy using computed tomography in patients with pancreatic neuroendocrine tumors.

Clinically effective methods to predict the efficacy of sunitinib, for patients with metastatic or locally advanced pancreatic neuroendocrine tumors (panNET) are scarce, making precision treatment difficult. This study aimed to develop and validate a computed tomography (CT)-based method to predict the efficacy of sunitinib in patients with panNET. Pretreatment CT images of 171 lesions from 38 patients with panNET were included. CT value ratio (CT value of tumor/CT value of abdominal aorta from the same patient) and radiomics features were extracted for model development. Receiver operating curve (ROC) with area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the proposed model. Tumor shrinkage of >10% at first follow-up after sunitinib treatment was significantly associated with longer progression-free survival (PFS; P < .001) and was used as the major treatment outcome. The CT value ratio could predict tumor shrinkage with AUC of 0.759 (95% confidence interval [CI], 0.685-0.833). We then developed a radiomics signature, which showed significantly higher AUC in training (0.915; 95% CI, 0.866-0.964) and validation (0.770; 95% CI, 0.584-0.956) sets than CT value ratio. DCA also confirmed the clinical utility of the model. Subgroup analysis showed that this radiomics signature had a high accuracy in predicting tumor shrinkage both for primary and metastatic tumors, and for treatment-naive and pretreated tumors. Survival analysis showed that radiomics signature correlated with PFS (P = .020). The proposed radiomics-based model accurately predicted tumor shrinkage and PFS in patients with panNET receiving sunitinib and may help select patients suitable for sunitinib treatment.

The role of quantitative tumor burden based on [68 Ga]Ga-DOTA-NOC PET/CT in well-differentiated neuroendocrine tumors: beyond prognosis.

PURPOSE: We aimed to elucidate the role of quantitative tumor burden based on PET/CT of somatostatin receptors in well-differentiated neuroendocrine tumors (NETs). METHODS: This study enrolled patients with [68 Ga]Ga-DOTA-NOC PET/CT-positive advanced NETs who did not receive medical treatment prior to PET/CT. Tumor burden was calculated using methods based on the background threshold and relative fixed threshold values (30%, 40%, and 50%). The prognostic value of the measured tumor burden in reference to overall survival (OS) and progression-free survival (PFS) on treatment with octreotide long-acting repeatable (LAR) was assessed using Cox regression analysis, Harrell's C-index, and survival analysis. A classification and regression tree (CART) was used to determine the optimal threshold for tumor burden. RESULTS: A total of 204 patients were included. Somatostatin receptor-expressing tumor volume (SRETV) and liver SRETV derived from a relative fixed threshold of 30% (SRETV30 and liver SRETV30) were statistically significantly associated with OS (C-index: 0.802 [95% confidence interval (CI), 0.658-0.946] and 0.806 [95% CI, 0.664-0.948], respectively). Extrahepatic tumor burden was not correlated with OS (hazard ratio: 0.617, 95% CI: 0.241-1.574, P = 0.312). Among 155 patients with non-functional NETs with a ki-67 index of ≤ 10%, those with a high SRETV30 (P = 0.016) or high liver SRETV30 (P = 0.014) showed statistically significantly worse PFS on treatment with octreotide LAR. Patients receiving a higher dose of octreotide LAR normalized by SRETV30 or liver SRETV30 (a normalized dose or a liver normalized dose) showed prolonged PFS on treatment with octreotide LAR and a prolonged OS. CONCLUSION: Quantitative tumor burden based on [68 Ga]Ga-DOTA-NOC PET/CT was correlated with OS and PFS in patients with non-functional NETs with a ki-67 index of ≤ 10% who received octreotide LAR. Calculating normalized and liver normalized doses may help in selecting the starting dose of octreotide LAR.

Human migration-based graph convolutional network for PM2.5 forecasting in post-COVID-19 pandemic age.

Due to the coronavirus disease 2019 pandemic, local authorities always implanted non-pharmaceutical interventions, such as maintaining social distance to reduce human migration. Besides, previous studies have proved that human migration highly influenced air pollution concentration in an area. Therefore, this study aims to explore whether human migration can work as a significant factor in the post-pandemic age to help PM2.5 concentration forecasting. In this work, we first analyze the variations of PM2.5 in 11 cities of Hubei from 2015 to 2020 and further compare PM2.5 trends with the migration trends of Hubei province in 2020. Experimental results indicate that the human migration indirectly affected the urban PM2.5 concentration. Then, we established a graph data structure based on the migration network describing the migration flow size between any two areas in the Hubei province and proposed a migration attentive graph convolutional network (MAGCN) for forecasting PM2.5. Combined with the migration data. The proposed model can attentively aggregate the information of neighbor nodes through migration weights. Experimental results indicate that the proposed MAGCN can forecast PM2.5 concentration accurately.

Asia-Pacific guidelines for managing functional dyspepsia overlapping with other gastrointestinal symptoms.

Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians.

Effective substances and mechanism of Yishen Guluo Mixture in treatment of chronic glomerulonephritis based on metabolomics and serum pharmacochemistry / 中国中药杂志

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.

Clinical Features and Outcomes of the Patients with B-Cell Chronic Lymphoproliferative Disease in the New Drug Era / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of the patients with B-cell chronic lymphoproliferative disease（B-CLPD） in the new drug era and the effect of new drug treatment on efficacy and survival.@*METHODS@#The clinical and laboratory data of 200 cases B-CLPD patients diagnosed between April 2015 and August 2021 were analyzed retrospectively. The clinical efficacy and survival of the patients under different treatments including Bruton tyrosine kinase（BTK） inhibitors， rituximab， and chemotherapy alone were analyzed. The prognostic factors affecting the survival of patients were analyzed by univarite analysis and multivariate analysis.@*RESULTS@#There were 119 male（59.5％） and 81 female（40.5%） in 200 cases B-CLPD patients， the sex ratio(male/female) was 1.5∶1 with median age of 61（30- 91） years old. The distribution of subtypes were as fallows: 51 cases (25.5%) of chronic lymphocytic leukemia/small lymphocytic lymphoma（CLL/SLL）， 64（32.0%） cases of follicular lymphoma（FL）， 40（20.0%） cases mantle cell lymphoma（MCL）， 30（15.0%） cases of marginal zone lymphoma（MZL）， 10（5%） cases of lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia（LPL/WM）， 5（2.5%） cases of B cell chronic lymphoproliferative disorders unclassified（B-CLPD-U） . The main clinical manifestation of 102 patients was lymph node enlargement, 32 cases were complicated with B symptoms. Among CLL/SLL patients， there were 12（23.5%） cases in Binet A and 39（76.5%） cases in Binet B/C. There were 29 patients（20.9%） in Ann Arbor or Lugano stage I-II and 110 cases（79.1%） in stage III-IV of other subtypes. The complete remission（CR） rate was 43.1%（25/58）， 40.2%（39/97）， 7.1%（1/14）， and overaIl response rate（ORR） was 87.9%（51/58）， 62.9%（61/97）， 28.6%（4/14） in the groups of BTK inhibitors， rituximab-based therapy， and chemotherapy alone. The 3-year OS rate and PFS rate in all patients was 79.2% and 72.4% respectively. The 3-year OS rate of patient with MZL, CLL/SLL, FL,WM was 94.7%, 87.7%, 86.8% and 83.3% respectively, while the 3-year OS rate of MCL was only 40.6%, which was significantly lower than other subtypes. The median OS of patients treated with BTK inhibitors and rituximab-based therapy was 20.5 and 18.5 months respectively， and the 3-year OS rate was 97.4% and 90.7%. However， the median PFS of patients receiving chemotherapy alone was 4 months， and the 1-year OS rate was 52.7%， which was statistically significant compared with the other two groups（P<0.05）. Univarite analysis showed that anemia， elevated lactate dehydrogenase， elevated β2-microglobulin， and splenomegaly were the poor prognostic factors for OS（P<0.05）， elevated lactate dehydrogenase was also poor prognostic factors for PFS（P<0.05）. Multifactor analysis showed that anemia and elevated lactate dehydrogenase were the independent poor prognostic factors for survival（P<0.05）.@*CONCLUSION@#The clinical features of B-CLPD was various， anemia and elevated lactate dehydrogenase are the prognostic factors for poor survival. BTK inhibitors and new immunotherapy can improve the survival and prognosis of patients in the new drug era.

Comparative analysis of the management practice of including designated retail pharmacies in the outpatient pooling of basic medical insurance / 中国卫生政策研究

Objective:To summarize and analyze the practice of the local practice on covering drugstore bills by pooled funds of basic medical insurance,and provide a reference for improving relevant policies.Methods:The medical insurance policies from various provinces,municipalities,autonomous regions,and coordination areas were systematically retrieved.ROST CM6 software was applied to analyze the high-frequency words and semantic network of the policy text,and combined with the interview and field investigation resultss,the key dimensions of the policy practice were identified and summarized.Then the regional differences,existing problems,and their causes were analyzed to put forward policy recommendations.Result:The selection of pharmacies covered in the payment system with outpatient expenses reimbursed by the pooled fund,the formulation of drug reimbursement list,the design of benefit plans,the management of drug prices and payments,and the supervision of hospital outflow prescriptions were five key dimensions of policy practice.There were significant differences in practice among different regions,and the problems mainly included the overall arrangement of covering pharmacies in the payment system,the mechanism of drug prices in pharmacies,and the coordination with other medical insurance policies.Conclusion:To improve the convenience of buying drugs for the insured,it is necessary to make full use of the advantages of pharmacies to meet the demand for outpatient medicine,promote the transparency of drug prices in pharmacies,coordinate the relevant medical insurance policies,strengthen the collaborative management between the healthcare security administration and relevant departments such as the health commission and the medical products administration,analyze and evaluate the potential effects of policy measures,and adjust policy measures promptly according to local conditions.

In vitro efficacy and combined drug sensitivity of lycosin-I against methicillin-resistant Staphylococcus aureus / 中华检验医学杂志

Objective:The aim of this study was to evaluate the in vitro activity of lysosin-Ⅰ against Methicillin-resistant Staphylococcus aureus (MRSA) and its synergistic effect with eight common antibacterial drugs against MRSA. Methods:This study was conducted following the design principles of a randomized controlled trials. Ten MRSA isolates, clinically isolated from the Second Xiangya Hospital of Central South University between September and November 2021, were determined the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bactericidal kinetic test of lycosin-Ⅰ in vitro anti-MRSA by micro-broth dilution method. Additionally, the micro-broth chessboard dilution method was utilized to evaluate the in vitro efficacy of lycosin-Ⅰ in combination with eight common antimicrobial agants, including penicillin, erythromycin, levofloxacin, gentamicin, rifampicin, minocycline, vancomycin, and linezolid. Results:The MIC range of lycosin-Ⅰ against MRSA was found to be between 4-8 mg/L with the MIC 50 and MIC 90 were 4 mg/L and 8 mg/L, respectively. The range of MBC was also between 4-8 mg/L, and the ratio of MBC/MIC was 1-2. The bactericidal kinetics test revealed that the number of surviving MRSA clinical isolates and standard strains initially decreased rapidly but then showed a resurgence when the concentration of lycosin-Ⅰ was 1/2 MIC or MIC. While, the bacterial load gradually reduced until complete elimination when the concentration was at 2 MIC or 4 MIC. The combination of lycosin-Ⅰ and gentamicin exhibited mainly synergistic effects, while the combination with other antibiotics showed mainly additive effects. Moreover, the combination of lycosin-Ⅰ and antibacterial drugs can significantly reduce the MIC 50 and MIC 90 of antibiotics. Conclusion:lycosin-Ⅰ has great antibacterial and bactericidal activity against MRSA in vitro with rapid and thorough sterilization effect and it can play a synergistic or additive role when combined with other antibacterial drugs against MRSA in vitro.

Clinical difference analysis and solution of lipid target and goal cut-off point determination of blood lipid management from different detection systems / 中华检验医学杂志

Objective:The results of the three lipid detection systems were compared to analyze their influence on risk stratification and clinical treatment in lipid management, especially the target goal cut-off point determination, and to find ways to reduce the impact on target goal determination of various lipid measurement system.Methods:A total of 196 serum samples with triglyceride TG <4.5 mmol/L were collected from people undergoing physical examinations and in-patients in the Second Xiangya Hospital of Central South University from August to October 2022. Triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were directly detected with Hitachi-Woke (HW), Roche and Mindray detection systems, respectively. The non high-density lipoprotein cholesterol (non HDL-C) was calculated by formula (TC-HDL-C) and LDL-C (F-LDL-C) was calculated by Friedewald formula, and results from various methodology were compared. The coefficient of variation ( CV) of these six indicators derived from the three detection systems were calculated to evaluate the consistency of the obtained results from different venders. In addition, the Pearson correlation coefficient was analyzed to evaluate the correlation of each indicator among different systems. According to the Chinese Guidelines for Blood Lipid Management, samples were divided into groups with LDL-C levels of <1.4, 1.4-<1.8, 1.8-<2.6, 2.6-<3.4 and ≥3.4 mmol/L according to the recommended LDL-C levels for different risk stratification levels. The sample size and percentage of LDL-C test results from different systems in the same group were counted to evaluate the impact of LDL-C differences between systems on clinical decision-making of blood lipid management. The correction factor was calculated through two methods: (1) The average deviation of LDL-C between systems was estimated by EP9-A3 method; (2) Multiple linear stepwise regression was used to establish the regression model of LDL-C difference and related indexes between systems. The two correction factors were used to correct the deviation of LDL-C value obtained from various systems, and Chi-square test was used to compare the difference of LDL-C grouping consistency rate before and after correction. Result:The average CV values of TG, TC, LDL-C, F-LDL-C, HDL-C, and non HDL-C among the three detection systems were 4.84%, 1.92%, 11.96%, 3.81%, 5.82% and 2.61%, respectively. Correlation analysis showed that when comparing the three systems in pairs, except for LDL-C derived from HW and Roche′s, and Mindray and Roche′s LDL-C ( R 2=0.938 and 0.947), the R 2 of other indicators were all greater than 0.97. The consistency rates of the three systems on LDL-C and F-LDL-C were 51.0% (100/196) and 90.8% (178/196), respectively, according to the risk stratification standard values and the difference was statistically significant ( P<0.05). When comparing in pairs, the consistency rates of Roche and HW, Mindray and HW, Mindray and Roche system LDL-C grouping were 60.7% (119/196), 82.7% (162/196), and 54.1% (106/196), respectively. After adjusting for mean deviation, the group consistency rate of Roche and HW increased to 73.7%-79.4% ( P<0.05), and the group consistency rate of Roche and Mindray increased to 72.3%-79.0% ( P<0.05). After adjusting for difference regression model, the group consistency rate of Roche and HW increased to 82.5%-84.0%, and the group consistency rate of Roche and Mindray increased to 81.0%-89.2%. However, there was no significant change in the group consistency rate of Mindray and HW after adjusting for both correction methods ( P>0.05) .Conclusions:There are significant differences in LDL-C derived from different detection systems, and the consistency rate of grouping according to the lipid-lowering standard value is relatively low, which may affect clinical decision-making in lipid management. Adjusted by the correction factor, the consistency rate of grouping between Roche and HW, Roche and Mindray systems with large differences in LDL-C can be improved. Using the difference multiple linear regression model as a correction factor is superior to the average deviation.