Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese medicine and Western medicine

Integrated traditional Chinese medicine(TCM)and Western medicine(WM)is a new medical science grounded in the knowledge bases of both TCM and WM,which then forms a unique modern medical system in China.Integrated TCM and WM has a long history in China,and has made important achievements in the process of clinical diagnosis and treatment.However,the methodological defects in currently published clinical practice guidelines(CPGs)limit its development.The organic integration of TCM and WM is a deeper integration of TCM and WM.To realize the progression of"integration"to"organic integration",a targeted and standardized guideline development methodology is needed.Therefore,the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Plasma microRNAs as potential new biomarkers for early detection of early gastric cancer

BACKGROUND Early gastric cancer(EGC), compared with advanced gastric cancer(AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method.AIM To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs(miRNAs) in EGC and AGC and compared them with those in benign gastritis(BG).METHODSWe examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR)confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, Helicobacter pylori(H. pylori)-negative gastritis(Control-1), and H. pylori-positive atrophic gastritis(Control-2).To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups.RESULTS Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of H. pylori-negative gastritis(Control-1) and H. pyloripositive atrophic gastritis(Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs,miR-7641, miR-425-5 p, miR-1180-3 p and miR-122-5 p, were used to effectively distinguish the Cancer group(EGC + AGC) from the Control group [area under the curve(AUC) = 0.799, 95% confidence interval(CI): 0.691-0.908, P < 0.001].Additionally, miR-425-5 p, miR-24-3 p, miR-1180-3 p and miR-122-5 p were utilized to distinguish EGC from the Control group(AUC = 0.829, 95%CI: 0.657-1.000, P =0.001). Moreover, the miR-24-3 p expression level in EGC was lower than that in the AGC(AUC = 0.782, 95%CI: 0.571-0.993, P = 0.029), and the miR-4632-5 p expression level in EGC was significantly higher than that in AGC(AUC = 0.791,95%CI: 0.574-1.000, P = 0.024).CONCLUSION The differentially expressed circulatory plasma miR-425-5 p, miR-1180-3 p, miR-122-5 p, miR-24-3 p and miR-4632-5 p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings.

Expression of transferrin in hematoma brain tissue at different stages after intra cerebral hemorrhage in rats

Objective: To explore the expression of transferrin(Tf) and transferrin receptor(Tf R) in hematoma brain tissue at different stage after intracerebral hemorrhage(ICH) in rats. Methods: ICH rats model were established by collagenase method, and rats were sacrificed at 24 h, 72 h, 7 d and 14 d after operation. The levels of Tf and Tf R in different periods of rats were detected by immunohistochemical method, and correlation between two groups was analyzed. Results: Tf, Tf R-positive cells at each time after operation in observation group were significantly higher than that in control group(P<0.05). Tf, Tf R-positive cells began to increase from 24 h after the operation and reached the peak 72 h-7 d after surgery, but then gradually decreased. Tf was mainly expressed in nucleus and cytoplasm of neurons and glial cells around the hematoma, but Tf R was mainly expressed in nucleus and cytoplasm of neurons and choroid plexus endothelial cells. Correlation analysis showed that the Tf-positive cell was significantly positively correlated with Tf R-positive cell expression(r=0.447, P=0.022). Conclusions: Tf and Tf R were important transporters in brain tissue excessive load iron transport after ICH, and detecting the expression levels of the two indicators can provide a reference for prognosis treatmentin ICH.

mi R-29a promotes hepatitis B virus replication and expression by targeting SMARCE1 in hepatoma carcinoma

AIM To investigate the functional role and underlying molecular mechanism of mi R-29 a in hepatitis B virus(HBV) expression and replication.METHODS The levels of mi R-29 a and SMARCE1 in HBV-infected Hep G2.2.15 cells were measured by quantitative real-time PCR and western blot analysis. HBV DNA replication was measured by quantitative PCR and Southern blot analysis. The relative levels of hepatitis B surface antigen and hepatitis B e antigen were detected by enzyme-linked immunosorbent assay. The Cell Counting Kit-8(CCK-8) was used to detect the viability of Hep G2.2.15 cells. The relationship between mi R-29 a and SMARCE1 were identified by target prediction and luciferase reporter analysis.RESULTS mi R-29 a promoted HBV replication and expression, w h i le S MA R C E 1 r e p r e s s e d H B V r e p lic a t io n a n d expression. Cell viability detection indicated that mi R-29 a transfection had no adverse effect on the host cells. Moreover, SMARCE1 was identified and validated to be a functional target of mi R-29 a. Furthermore, restored expression of SMARCE1 could relieve the increased HBV replication and expression caused by mi R-29 a overexpression.CONCLUSION mi R-29 a promotes HBV replication and expression through regulating SMARCE1. As a potential regulator of HBV replication and expression, mi R-29 a could be a promising therapeutic target for patients with HBV infection.

Expression and effect of sodium-potassium-chloride cotransporter on dorsal root ganglion neurons in a rat model of chronic constriction injury

Sodium-potassium-chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) are associated with the transmission of peripheral pain.We investigated whether the increase of NKCC1 and KCC2 is associated with peripheral pain transmission in dorsal root ganglion neurons.To this aim,rats with persistent hyperalgesia were randomly divided into four groups.Rats in the control group received no treatment,and the rat sciatic nerve was only exposed in the sham group.Rats in the chronic constriction injury group were established into chronic constriction injury models by ligating sciatic nerve and rats were given bumetanide,an inhibitor of NKCC1,based on chronic constriction injury modeling in the chronic constriction injury + bumetanide group.In the experiment measuring thermal withdrawal latency,bumetanide (15 mg/kg) was intravenously administered.In the patch clamp experiment,bumetanide (10 μg/μL) and acutely isolated dorsal root ganglion neurons (on day 14) were incubated for 1 hour,or bumetanide (5 μg/μL) was intrathecally injected.The Hargreaves test was conducted to detect changes in thermal hyperalgesia in rats.We found that the thermal withdrawal latency of rats was significantly decreased on days 7,14,and 21 after model establishment.After intravenous injection of bumetanide,the reduction in thermal retraction latency caused by model establishment was significantly inhibited.Immunohistochemistry and western blot assay results revealed that the immune response and protein expression of NKCC1 in dorsal root ganglion neurons of the chronic constriction injury group increased significantly on days 7,14,and 21 after model establishment.No immune response or protein expression of KCC2 was observed in dorsal root ganglion neurons before and after model establishment.The Cl^– (chloride ion) fluorescent probe technique was used to evaluate the change of Cl^– concentration in dorsal root ganglion neurons of chronic constriction injury model rats.We found that the relative optical density of N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (a Cl^– fluorescent probe whose fluorescence Cenintensity decreases as Cl– concentration increases) in the dorsal root ganglion neurons of the chronic constriction injury group was significantly decreased on days 7 and 14 after model establishment.The whole-cell patch clamp technique revealed that the resting potential and action potential frequency of dorsal root ganglion neurons increased,and the threshold and rheobase of action potentials decreased in the chronic constriction injury group on day 14 after model establishment.After bumetanide administration,the above indicators were significantly suppressed.These results confirm that CCI can induce abnormal overexpression of NKCC1,thereby increasing the Cl^– concentration in dorsal root ganglion neurons;this then enhances the excitability of dorsal root ganglion neurons and ultimately promotes hyperalgesia and allodynia.In addition,bumetanide can achieve analgesic effects.All experiments were approved by the Institutional Ethics Review Board at the First Affiliated Hospital,College of Medicine,Shihezi University,China on February 22,2017 (approval No.A2017-169-01).

Effects of lilalutine on blood glucose, lipid, blood pressure and carotid plaque in patients with type 2 diabetes mellitus complicated with atherosclerosis

Objective: To evaluate the clinical effect of Lilalutide in the treatment of type 2 diabetes mellitus with atherosclerosis and its effects on blood glucose, blood lipid, blood pressure and carotid plaque. Methods: 82 patients with type 2 diabetes complicated with atherosclerosis who were treated in our hospital from March 2017 to August 2018 were selected. The patients were randomly divided into control group and observation group with 41 cases in each group. All patients were given diet and exercise intervention and oral statins. On this basis, the control group was treated with metformin, the observation group was treated with Liraglutide, and the two groups were treated continuously for 6 months. The fasting blood glucose (FPG), postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), Body mass index (BMI), body mass, waist circumference, and carotid plaque (soft plaque, flat plaque, hard plaque, mixed plaque) were observed before and after treatment. The curative effect and the incidence of major adverse reactions between the two groups were compared. Results: The total effective rate of the observation group was higher than that of the control group. After treatment, the 2hPG, HbA1c and FPG in the observation group were lower than those in the control group;the TG, TC and LDL-C were lower than those in the control group, while HDL-C was higher than that in the control group;the SBP and DBP were lower than those in the control group. the body mass, waist circumference and BMI were lower than those of control group;the IMT was lower than that in the control group;plaque detection rate was lower than that in the control group. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusion: Liraglutide is effective in treating type 2 diabetes mellitus with atherosclerosis. It has obvious advantages in improving blood sugar, blood lipid, blood pressure and weight control, and does not increase adverse drug reactions. It is worthy of clinical application.

Spatial distribution patterns of anorectal atresia/stenosis in China:Use of two-dimensional graph-theoretical clustering

AIM:To investigate the spatial distribution patterns of anorectal atresia/stenosis in China.METHODS:Data were collected from the Chinese Birth Defects Monitoring Network(CBDMN),a hospital-based congenital malformations registry system.All fetuses more than 28 wk of gestation and neonates up to 7 d of age in hospitals within the monitoring sites of the CBDMN were monitored from 2001 to 2005.Two-dimensional graph-theoretical clustering was used to divide monitoring sites of the CBDMN into different clusters according to the average incidences of anorectal atresia/stenosis in the different monitoring sites.RESULTS:The overall average incidence of anorectal atresia/stenosis in China was 3.17 per 10000 from 2001 to 2005.The areas with the highest average incidences of anorectal atresia/stenosis were almost always focused in Eastern China.The monitoring sites were grouped into 6 clusters of areas.Cluster 1 comprised the monitoring sites in Heilongjiang Province,Jilin Province,and Liaoning Province;Cluster 2 was composed of those in Fujian Province,Guangdong Province,Hainan Province,Guangxi Zhuang Autonomous Region,south Hunan Province,and south Jiangxi Province;Cluster 3 consisted of those in Beijing Municipal City,Tianjin Municipal City,Hebei Province,Shandong Province,north Jiangsu Province,and north Anhui Province;Cluster 4 was made up of those in Zhejiang Province,Shanghai Municipal City,south Anhui Province,south Jiangsu Province,north Hunan Province,north Jiangxi Province,Hubei Province,Henan Province,Shanxi Province and Inner Mongolia Autonomous Region;Cluster 5 consisted of those in Ningxia Hui Autonomous Region,Gansu Province and Qinghai Province;and Cluster 6 included those in Shaanxi Province,Sichuan Province,Chongqing Municipal City,Yunnan Province,Guizhou Province,Xinjiang Uygur Autonomous Province and Tibet Autonomous Region.CONCLUSION:The fi ndings in this research allow the display of the spatial distribution patterns of anorectal atresia/stenosis in China.These will have important guiding significance for further analysis of relevant environmental factors regarding anorectal atresia/ stenosis and for achieving regional monitoring for anorectal atresia/stenosis.

Injected spectrum for TeV γ-ray emission from the galactic center

The detection of very high energy γ-ray emission from the Galactic center has been reported by four independent groups. One of these γ-ray sources, the 10 TeV -γ-ray radiation reported by HESS, has been suggested as having a hadronic origin when relativistic protons are injected into and interact with the dense ambient gas. Assuming that such relativistic protons required by the hadronic model come from the tidal disruption of a star by the massive black hole of Sgr A＊, we explore the spectrum of the relativis- tic protons. In the calculations, we investigate cases where different types of stars are tidally disrupted by the black hole of Sgr A＊, and we consider that different diffusion mechanisms are used for the propagation of protons. The initial energy distribution of the injected spectrum of protons is assumed to follow a power-law with an exponential cut-off, and we derive the different indices of the injected spectra for the tidal disruption of different types of stars. For the best fit to the spectrum of photons detected by HESS, the spectral index of the injected relativistic protons is about 2.05 when a red giant is tidally disrupted by the black hole of Sgr A＊ and the diffusion mechanism is the Effective Confinement of Protons.

A clinical study on the prevention of phlebitis caused by Cinobufagin using hand exercise combined with Jinhuang ointment

Objective:The aim of this study is to observe the clinical effect of hand exercise combined with jinhuang ointment on the prevention of phlebitis due to cinobufagin.Methods:A total of 90 cancer patients who have been receiving intravenous(Ⅳ)infusion of cinobufagin from May 2018 to June 2019 in the oncology department of our hospital were selected.They were then divided into three groups in a random manner,which include 30 cases in the control group,30 cases in the jinhuang ointment group,and 30 cases in the group of hand exercise combined with jinhuang ointment.The control group had a routine care before cinobufagin was infused from the first day of hospitalization.During the routine care mentioned previously,the jinhuang ointment group was given locally jinhuang ointment inunction,qd,and kept for 6 hours.Hand exercises were then done on the combined group excluding jinhuang ointment application,qd,at 10min.After treatment for 1 week,the phlebitis and pain incidences on the venipuncture site were then compared between the three groups.Results:After the 1-week treatment,the incidences of grade Ⅰ/Ⅱ phlebitis in the control group,the jinhuang ointment group,and the group of hand exercise combined with jinhuang ointment were 53.5%,23.3%,and 10%,respectively.The results have shown a significant decrease in the jinhuang ointment group and the combined group as in comparison with the control group(P=0.0169,P=0.0003).Even with the incidence of the combined group being lower than that of the jinhuang ointment group,no statistically significant difference(P=0.1659)was found.The incidences of grade Ⅲ/Ⅳ phlebitis in the control group,the jinhuang ointment group,and the group of hand exercise combined with jinhuang ointment were 23.3%,3.3%,and 3.3%,respectively.Both the jinhuang ointment group and the combined group had significantly lower results than that of the control group(P=0.0003,P=0.0227).There was no difference in the results of the combined group and the jinhuang ointment group.The incidences of pain in the control group,the jinhuang ointment group,and the group of hand exercise combined with jinhuang ointment were 56.7%,36.7%,and 20%,respectively.There was no significant difference in the results of the jinhuang ointment group and the control group(P=0.1205);the combined group has shown a significant decrease in the incidence compared with the control group(P=0.0035);the incidence of pain in the combined group was lower than that of the jinhuang ointment group,but without a statistical difference(P=0.1520).Conclusion:Hand exercise together with jinhuang ointment inunction can significantly reduce the incidence of phlebitis produced by cinobufagin.

Impact of task-oriented training based on acupuncture rehabilitation on upper extremity function and quality of life of patients with early stroke

BACKGROUND Eighty percent of stroke patients develop upper limb dysfunction,especially hand dysfunction,which has a very slow recovery,resulting in economic burden to families and society.AIM To investigate the impact of task-oriented training based on acupuncture therapy on upper extremity function in patients with early stroke.METHODS Patients with early stroke hemiplegia who visited our hospital between January 2021 and October 2022 were divided into a control group and an observation group,each with 50 cases.The control group underwent head acupuncture plus routine upper limb rehabilitation training(acupuncture therapy).In addition to acupuncture and rehabilitation,the observation group underwent upper limb task-oriented training(30 min).Each group underwent treatment 5 d/wk for 4 wk.Upper extremity function was assessed in both groups using the Fugl-Meyer Assessment-Upper Extremity(FMA-UE),Wolf Motor Function Rating Scale(WMFT),modified Barthel Index(MBI),and Canadian Occupational Performance Measure(COPM).Quality of life was evaluated using the Short-Form 36-Item Health Survey(SF-36).Clinical efficacy of the interventions was also evaluated.RESULTS Before intervention,no significant differences were observed in the FMA-UE,MBI,and WMFT scores between the two groups(P>0.05).After intervention,the FMA-UE,WMFT,MBI,COPM-Functional Mobility and Satisfaction,and SF-36 scores increased in both groups(P<0.05),with even higher scores in the observation group(P<0.05).The observation group also obtained a higher total effective rate than the control group(P<0.05).CONCLUSION Task-oriented training based on acupuncture rehabilitation significantly enhanced upper extremity mobility,quality of life,and clinical efficacy in patients with early stroke.

On the Blowing up of Solutions to One-dimensional Quantum Navier-Stokes Equations

The blow-up in finite time for the solutions to the initial-boundary value problem associated to the one-dimensional quantum Navier-Stokes equations in a bounded domain is proved. The model consists of the mass conservation equation and a momentum balance equation, including a nonlinear third-order differen- tial operator, with the quantum Bohm potential, and a density-dependent viscosity. It is shown that, under suitable boundary conditions and assumptions on the initial data, the solution blows up after a finite time, if the viscosity constant is not bigger than the scaled Planck constant. The proof is inspired by an observable constructed by Gamba, Gualdani and Zhang, which has been used to study the blowing up of solutions to quantum hydrodynamic models.

Standardizing Individualized Efficacy Evaluation to Optimize Evidence-Using Pattern in Traditional Chinese Medicine-Preliminarily Establishing Traditional Chinese Medicine Evidence-based Case Reporting System

Individualized treatment is a basic feature of Traditional Chinese Medicine(TCM), and individualized efficacy evaluation is also emphasized in TCM clinical practice. Individualized evaluation is in favor of improving intervention continuously, and optimizing the TCM evidenceusing pattern gradually. Traditional case reports can better demonstrate the efficacy of individual, but lack of standardized design, making such evidence show a lower quality. Meanings, objectives and design elements of TCM individualized evaluation were discussed in this paper.Then based on the original work, design ideas and framework of TCM evidence-based case reporting system were established preliminarily.This work will improve the methodology of TCM individualized evaluation to realize the goal of optimizing TCM clinical evidence-using pattern.

The add-on effect of a Chinese herbal formula for patients with resistant hypertension: study protocol for a pilot cohort study

BACKGROUND： Despite a recent American Heart Association （AHA） consensus statement emphasizing the importance of resistant hypertension （RH）, its control is still a challenge for conventional medicine. The Chinese herbal formula, Qutan Huayu Fang, has been used effectively to assist antihypertensive agents in blood pressure control, but its effect for RH patients is still unclear. This pilot study aims to explore the effects of taking the formula in addition to antihypertensive medication in the management of RH. METHODS/DESIGN： A prospective cohort study will be conducted in two first-class hospitals of traditional Chinese medicine （TCM）. Eligible RH patients will be classified as the experimental group （n = 100） and the control group （n = 100） based on the interventions they receive. Participants taking antihypertensive agents and the Chinese herbal formula will be in the experimental group and those taking antihypertensive agents alone will be in the control group. The whole study will last 24 weeks, including an 8-week observation and follow-up at 24 weeks. The primary outcomes, assessed against patient baseline conditions, will be the reduction of systolic blood pressure and diastolic blood pressure as well as changes in TCM symptoms and signs. These outcomes will be assessed at weeks 2, 4, 6, and 8. The reductions of blood pressure will also be assessed at week 24. Cardiac events and mortality rate will be secondary outcomes and will be assessed at weeks 8 and 24. Any adverse reactions will be recorded during the study. The causal inference method will be used to assess the effectiveness of the inclusion of TCM herbal medicine in the management of patients with RH. DISCUSSION： This study will determine whether the Chinese herbal formula is helpful for RH patients treated with antihypertensive agents and the findings will provide a basis for further confirmatory studies TRIAL REGISTRATION NUMBER： ClinicalTria/s.gov Identifier NCT01904695

Prognostic value of tissue inhibitor of metalloproteinase-matrix metalloproteinase biomarkers at 30 days in patients with acute myocardial infarction without reperfusion therapy

To the Editor:Ischemic coronary artery disease is the leading cause of heart failure(HF)which is a major public health burden worldwide.Over the past decades,development of new pharmacological therapies and implementation of early reperfusion strategies have contributed to a significant reduction in mortality associated with acute myocardial infarction(AMI).However,improved survival in acute cardiac ischemic event has expanded the pool of patients prone to cardiac remodeling and adverse cardiovascular(CV)outcomes.