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The continuous development of high-throughput and single-cell sequencing technologies and the emergence of spatial transcriptome sequencing have allowed the continuous discovery of temporal and spatial molecular events in the progression of colorectal cancer (CRC) to better understand its mechanism of malignant progression. Genetic variations (mutation of APC and P53, etc.) and mismatch repair of DNA, posttranscriptional regulation, such as epigenetic alteration, and dynamic alteration of complex molecular networks have their own special molecules that play key roles. Drug resistance and metastasis in the late stage of CRC progression are closely related to these key molecular events. This article reviews the research progress and explores key molecular events in the malignant progression of CRC to provide scientific basis and ideas for elucidating the regulatory mechanism of CRC and evaluating its prognosis prediction and treatment.
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Objective: To analyze the global epidemiology of renal cell carcinoma (RCC) in 2020. Methods: The incidence and mortality data of RCC in the cooperative database GLOBOCAN 2020 of International Agency for Research on Cancer of WHO and the human development index (HDI) published by the United Nations Development Programme in 2020 were collated. The crude incidence rate (CIR), age-standardized incidence rate (ASIR), crude mortality rate (CMR), age-standardized mortality rate (ASMR) and mortality/incidence ratio (M/I) of RCC were calculated. Kruskale-Wallis test was used to analyze the differences in ASIR or ASMR among HDI countries. Results: In 2020, the global ASIR of RCC was 4.6/100 000, of which 6.1/100 000 for males and 3.2/100 000 for females and ASIR was higher in very high and high HDI countries than that in medium and low HDI countries. With the rapid increase of age after the age of 20, the growth rate of ASIR in males was faster than that in females, and slowed down at the age of 70 to 75. The truncation incidence rate of 35-64 years old was 7.5/100 000 and the cumulative incidence risk of 0-74 years old was 0.52%. The global ASMR of RCC was 1.8/100 000, 2.5/100 000 for males and 1.2/100 000 for females. The ASMR of males in very high and high HDI countries (2.4/100 000-3.7/100 000) was about twice that of males (1.1/100 000-1.4/100 000) in medium and low HDI countries, while the ASMR of female (0.6/100 000-1.5/100 000) did not show significant difference. ASMR continued to increase rapidly with age after the age of 40, and the growth rate of males was faster than that of females. The truncation mortality rate of 35-64 years old was 2.1/100 000, and the cumulative mortality risk of 0-74 years old was 0.20%. M/I decreases with the increase of HDI, with M/I as 0.58 in China, which was higher than the global average of 0.39 and the United States' 0.17. Conclusion: The ASIR and ASMR of RCC presented significant regional and gender disparities globally, and the heaviest burden was in very high HDI countries.
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Male , Humans , Female , Adult , Middle Aged , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Young Adult , Aged , Carcinoma, Renal Cell/epidemiology , Incidence , Databases, Factual , China , Kidney Neoplasms/epidemiology , Global HealthABSTRACT
OBJECTIVE To compare the clinical comprehensive value of 15 Chinese patent medicines for the treatment of chronic hepatitis B， in order to provide reference for clinical rational drug use. METHODS According to the Management Guidelines for Clinical Comprehensive Evaluation of Pharmaceuticals （2021 Version for Trial Implementation）， systematic literature review， meta-analysis and other related data analysis methods were used to perform qualitative and quantitative analysis for the safety， efficacy， economy， suitability， accessibility and innovation of 15 Chinese patent medicines. RESULTS In terms of safety， most of the adverse drug reactions of chronic hepatitis B Chinese patent medicines before the market were unobserved or unclear； post-marketing safety took nucleoside analogs as the intermediate bridge for meta-analysis， there was no significant difference in the incidence of adverse drug reactions among the combined regimens of Chinese patent medicines （P＞0.05）， except that the combination regimen of Fuzheng huayu capsule， Compound yiganling capsules versus combination regimen of Jiuwei gantai capsules showed statistically significant differences （P＜0.05）. In terms of effectiveness， the results of network meta-analysis showed that most Chinese patent medicines， such as Fuzheng huayu capsules combined regimens， had no significant differences in effective rate， HBeAg negative conversion rate and HBV-DNA negative conversion rate （P＞0.05）； however， in reducing the liver elastic hardness value， the combined regimen of Dangfei liganning tablet （capsule） was better than the other combined regimens （P＜0.05）. In terms of economy， the highest cost was the Shuganning injection， and the lowest was Hepatitis B qingre jiedu granules. In terms of suitability， most of the medicines were capsules， tablets and granules， which only needed to be sealed to store and taken orally or taken with boiling water. Compared with injections and some similar products that required strict control of storage temperature， its suitability was better. In terms of accessibility， from the perspective of drug price and affordability， Shuganning injection had the highest average daily cost， the number of days that needed to be borne by the average daily wage was the highest； the average daily cost of Compound yiganling tablets was the lowest， and the number of days required to be borne by the average daily wage was the lowest. From the perspective of availability， Compound biejia ruangan tablets， Dangfei liganning capsules and Wuzhi granules were easier to obtain. In terms of innovation， the 15 Chinese patent medicines included in the study were all domestically produced medicines with a relatively long-term theoretical basis of traditional Chinese medicine and experience in human medicine， and had good industrial innovation. Among them， Compound huayu tablets （capsules） and Anluo huaxian pills were protected varieties of traditional Chinese medicine； Fuzheng huayu tablets （capsules） with more patents had 6 valid patents， all of which were patents for invention. CONCLUSIONS Wuzhi capsule， Sedum sarmentosum granules， Compound yiganling tablets， Rhubarb buchong pills and Dangfei liganning capsules have high clinical comprehensive value.
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OBJECTIVE To provide reference for perfecting prescription circulation service and related platforms construction and improving online medical service level. METHODS A questionnaire was designed after literature review and consulting expert opinions. Patients who had received prescription circulation service in the prescription circulation platform of a Grade-A third-class hospital in Sichuan Province from November 22， 2019 to May 2022 were randomly selected， and the knowledge， attitude and practice of prescription circulation service were investigated by questionnaires， which were sent through telephone contact and short message. RESULTS A total of 285 patients were investigated， and the number of effective responses was 200. Most of the surveyed patients in prescription circulation service for 1-5 times in the past year （129 cases， 64.50%）； 77.0% of the patients had a “general understanding” or “no understanding” of prescription circulation services， and the main prescription circulation services they received were online consultation service （169 cases， 84.50%） and drug delivery service （106 cases， 53.00%）. The average waiting time and expected waiting time were 1-5 min. The services with the largest number of demand （145 cases， 72.50%） and the highest demand （3.585 points） were drug delivery services. Most of the respondents’ willingness to pay was “general willingness” （83 cases， 41.50%）， and most of the patients were willing to pay less than or equal to 5 yuan per time （92 cases， 46.00%）. Totally 73.0% of the surveyed patients were “satisfied” or “relatively satisfied” with the prescription transfer service. The results of univariate analysis showed that the main factors influencing patients’ satisfaction with prescription circulation service were service awareness， service waiting time， patients’ demand satisfaction and patients’ willingness to pay. CONCLUSIONS The surveyed patients are generally satisfied with prescription circulation service， and the service content with high satisfaction is drug distribution service， and patients are willing to pay a lower price for prescription circulation service. It is suggested that relevant departments should strengthen the publicity of prescription circulation service， improve the content of prescription circulation service and reduce the payment price of prescription circulation service， so as to improve the operation efficiency of Chinese medical system while facilitating patients.
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OBJECTIVE To provide reference for the access to medical insurance for rare diseases in China based on the existing access pathway and framework by analyzing the access policy of medical insurance for rare diseases in the United Kingdom （UK）. METHODS After collecting relevant guidelines and policy documents related to drug use for rare diseases in the UK， content analysis method was used to analyze the evaluation mechanism of drug use for rare diseases， reimbursement decision- making standards， stakeholder participation， coping strategies for dealing with uncertainties and risks， and policy implementation effects， and extract the key points of medical insurance access for drug use for rare diseases in the UK， to provide some suggestions for the establishment of medical insurance access system for rare diseases in China. RESULTS & CONCLUSIONS From the perspective of access， the UK had adopted a separate approach and clear criteria to assess and reimburse drugs for rare diseases. From the perspective of evaluation mechanism， multi-stakeholders such as doctors， patients and applicants participated in the decision-making process in the UK. The UK addressed uncertainty and risk by gathering better clinical evidence and using the patient access programme. After the implementation of the policy related to drug use for rare diseases， the UK had achieved remarkable results in terms of funding for drug use for rare diseases， the reimbursement rate of drug application， and the number of funded patients. It is suggested that in the process of establishing and improving the evaluation and reimbursement system for rare diseases drugs in China， the availability of rare diseases drugs should be improved by establishing a separate access assessment path for rare diseases drugs and involving more stakeholders.
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Background@#We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals. @*Objective@#To explore the role and mechanism of miR-1246 in severe AA. @*Methods@#Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+ IL-17+ cells proportion. ELISA was used to measure cytokine levels. @*Results@#miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples.NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+ IL-17+ cells proportion and the IL-17F level. @*Conclusion@#miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.
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OBJECTIVE To explore the influential factors for “Internet +” prescription circulation and construction specifications of prescription circulation platform， so as to provide reference for the government to formulate relevant policies and standardized construction of prescription circulation platform. METHODS Stakeholders in the process of prescription circulation service in medical institutions in Sichuan province were selected to conduct key insider interviews， and grounded theory was used to analyze the data. RESULTS The influential factors of prescription circulation could be divided into three aspects： participant factor， administrative decision factor and information technology factor. The influential factors of prescription circulation mainly lay in pharmacy admission and withdrawal mechanism， medical insurance reimbursement service， supporting policies and pharmaceutical care ability. In terms of pharmacy admission and withdrawal mechanism， pharmacy qualification， pharmaceutical service personnel， drug allocation and distribution should be considered to unify pharmacy admission standards； in terms of medical insurance reimbursement service， it should actively connect with social pharmacies to realize the transfer of prescription medical insurance reimbursement from designated pharmacies； in terms of supporting policies， it should pay attention to the construction of the top-level design of prescription circulation； in terms of pharmaceutical care ability， regular training and assessment of licensed pharmacists should be performed in drug consultation， prescription review and other pharmaceutical care. CONCLUSIONS Participants have more influence on prescription circulation， and pharmacy admission and withdrawal mechanism and pharmaceutical care ability need to be improved. There are various types of prescription circulation platform construction， but each has its own advantages and disadvantages. It is suggested that relevant government departments should improve the access threshold of pharmacies， follow up medical insurance reimbursement services and supporting policies， and explore ways to improve pharmaceutical care capacity， leading and issuing relevant policies and measures to promote the prescription circulation service and make the “Internet +” prescription circulation develop in an orderly manner.
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ObjectiveTo compare the annual and age trends of the age-standard incidence rate （ASIR） and the age-standard mortality rate （ASMR） of lung cancer in countries with different human development index （HDI） from 1990 to 2019. MethodsThe data were collected from the global burden of disease study and GLOBOCAN 2020. The average annual percentage change （AAPC） and age trends of ASIR and ASMR in lung cancer were analyzed by the Joinpoint regression model， and the comparison between the four groups was analyzed by Kruskale-Wallis analysis. ResultsIn 2020， the incidence and mortality of lung cancer gradually increased with age and HDI grade. From 1990 to 2019， the global ASIR and ASMR of lung cancer decreased， and the ASIR of lung cancer among male decreased， while the ASIR of lung cancer among female increased. The results showed that ASIR of lung cancer in female residents in countries with very high HDI increased significantly from 1996 to 2011， resulting in an overall upward trend in female ASIR， while the other groups showed a downward trend. It was found that ASIR and ASMR of lung cancer in China and India were on the rise， while ASIR and ASMR of lung cancer in Russia and the United States were on the decline. ConclusionAlthough very high/high HDI countries face a higher burden of lung cancer occurrence and death， the accumulation of lung cancer burden is completed in the transitioning period. Therefore， lung cancer prevention measures in countries in transition are critical for global lung cancer control.
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When facing two or more choices， sound decision-making is critical. In the field of clinical medical practice and public health， more and more researchers use decision-making analysis as an important tool to assist in making the optimal choices. Public health emergencies have the characteristics of group cases， sudden and uncertain. In addition to causing serious damage to public health， they may also have varying degrees of impact on socio-economic， psychological and even social stability. At present， we have not seen the application of mature and sound decision analysis in public health emergency response. This paper reviewed the development of decision analysis in the medical field and the application of common decision-making models in clinical practice. Combined with the current situation of global infectious disease outbreaks and prevention and control， this paper puts forward the concepts and prospects of establishing an auxiliary decision-making system for public health emergencies， aiming to provide a scientific method for medical and health workers to respond to public health emergencies.
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Objective:To analyze the clinical characteristics and evaluate the effect and safety of anti-vascular endothelial growth factor (VEGF) therapy in retinopathy of prematurity (ROP) in Sichuan province.Methods:A retrospective study. From January 2013 to January 2022, 156 patients (306 eyes) with ROP who received intravitreal anti-VEGF therapy for the first time in the Department of Ophthalmology, West China Hospital of Sichuan University were selected. According to the type of anti-VEGF drugs, the children were divided into intravitreal injection of ranibizumab (IVR) group and intravitreal injection of conbercept (IVC) group; IVC group was divided into hospital group and referral group according to the different paths of patients. After treatment, the patients were followed up until the disease degenerated (vascular degeneration or complete retinal vascularization) or were hospitalized again for at least 6 months. If the disease recurred or progressed, the patients were re-admitted to the hospital and received anti-VEGF drug treatment, laser treatment or surgical treatment according to the severity of the disease. Clinical data of these children was collected, including general clinical characteristics: gender, gestational age at birth (GA), birth weight (BW), history of oxygen inhalation; pathological condition: ROP stage, zone, whether there were plus lesions; treatment: treatment time, postmenstrual gestational age at the time of the first anti-VEGF drug treatment; prognosis: re-treat or not, time of re-treatment, mode of re-treatment; adverse events: corneal edema, lens opacity, endophthalmitis, retinal injury, and treatment-related systemic adverse reactions. The measurement data between groups were compared by t test, and the count data were compared by χ2 test or rank sum test. Results:Of the 306 eyes of 156 children with ROP, 74 were male (47.44%, 74/156) and 82 were female (52.56%, 82/156). Each included child had a history of oxygen inhalation at birth. The GA was (28.43±2.19) (23.86-36.57) weeks, BW was (1 129±335) (510-2 600) g, and the postmenstrual gestational age was (39.80±3.04) (31.71-49.71) weeks at the time of the first anti-VEGF drug treatment. All patients were diagnosed as type 1 ROP, including 26 eyes (8.50%, 26/306) of aggressive ROP (A-ROP), 39 eyes (12.74%, 39/306) of zone Ⅰ lesions, and 241 eyes (78.76%, 241/306) of zone Ⅱ lesions. The children were treated with intravitreal injection of anti-VEGF drugs within 72 hours after diagnosis. Among them, 134 eyes (43.79%, 134/306) of 68 patients were treated with IVR, and 172 eyes (56.21%, 172/306) of 88 patients were treated with IVC. In IVC group, 67 eyes of 34 patients (38.95%, 67/172) were in the hospital group and 105 eyes of 54 patients (61.05%, 105/172) were in the referral group. 279 eyes (91.18%, 279/306) were improved after one treatment, 15 eyes (4.90%, 15/306) were improved after two treatments, and 12 eyes (3.92%, 12/306) were improved after three treatments. The one-time cure rate of IVR group was lower than that of IVC group, but the difference was not statistically significant ( χ2=1.665, P=0.197). In different ROP categories, IVC showed better therapeutic effect in A-ROP, and its one-time cure rate was higher than that in IVR group, with statistically significant difference ( χ2=7.797, P<0.05). In the hospital group of IVC group, the GA, BW and the postmenstrual gestational age at first time of anti-VEGF drug treatment were lower than those in the referral group, and the difference was statistically significant ( t=-2.485, -2.940, -3.796; P<0.05). The one-time cure rate of the hospital group and the referral group were 94.94%, 92.38%, respectively. The one-time cure rate of the hospital group was slightly higher than that of the referral group, but the difference was not statistically significant ( χ2=0.171, P=0.679). In this study, there were no ocular and systemic adverse reactions related to drug or intravitreal injection in children after treatment. Conclusions:Compared with the characteristics of ROP in developed countries, the GA, BW and postmenstrual gestational age of the children in Sichuan province are higher. Both IVR and IVC can treat ROP safely and effectively. There is no significant difference between the two drugs in the overall one-time cure effect of ROP, but IVC performed better in the treatment of A-ROP in this study.
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Objective:Based on experience of robotic gastrointestinal surgery at the Department of General Surgery, Clinical Medicine Center of Gansu Provincial Hospital, this study explored the principles and methods of trocar layout for robotic "3+2" mode gastrointestinal surgery, suitable for beginners.Methods:From Apr 2017 to Oct 2022, the robotic gastrointestinal surgery team of Gansu Provincial Hospital completed 998 cases of robotic "3+2" mode gastrointestinal surgery, including 600 cases of gastric cancer, 100 cases of rectal cancer, 98 cases of descending colon and sigmoid colon cancer, 20 cases of transverse colon cancer, and 180 cases of right colon cancer. Through the continuous optimization and improvement of the problems encountered during the operation, combined with the operator's experience, and taking into account various aspects, we developed the robotic "3+2" mode trocar layout for gastrointestinal surgery.Results:Four principles of trocar layout were developed, namely, the principle of lens placement around the navel, the principle of symmetry in the main operation, the principle of 8-10cm distance between trocar holes, and the principle of symmetry in the auxiliary hole lens. Three trocar layout methods and principles applicable to robotic gastric surgery, and four applicable to robotic colorectal surgery were developed.Conclusion:The trocar layout method of robotic "3+2" mode gastrointestinal surgery is established based on a large number of robotic gastrointestinal surgery experiences. This method is simple and easy to learn, with strong repeatability and operability.
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Objective:To analyze the risk factors and prognosis of endoleak after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm.Methods:The clinical data of patients with infrarenal abdominal aortic aneurysms treated by endovascular repair at the Department of Vascular Surgery,the First Affiliated Hospital of Guangxi Medical University from Jun 2012 to Nov 2021 were retrospectively analyzed.Results:During the first follow-up CTA after surgery,136 out of 299 patients had endoleak.A total of 186 patients had at least one CTA reexamination after discharge. Statistical analysis showed that excessive neck angulation was an independent risk factor for type Ⅰa endoleak ( t=-6.108, P<0.001), wider common iliac artery diameter (left Z=-2.787, P=0.005, Right Z=-2.381, P=0.017) and iliac aneurysm ( χ2=6.398, P=0.011) were risk factors for type Ⅰb endoleak. The survival time of patients in endoleak group was similar to no endoleak group. Conclusions:Excessive neck angulation is an independent risk factor for type Ⅰa endoleak. Most leaks resolve spontaneously ,the prognosis is fair.
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OBJECTIVE To provide reference for the prevention and treatment of hepatitis C and the formulation and improvement of medical insurance payment policy for direct-acting antiviral （DAA） drugs. METHODS An questionnaire survey was conducted among the patients who received hepatitis C treatment in a third-grade class-A hospital in Sichuan province from 2019 to 2020 and enjoyed Chengdu medical insurance policy. The patients’ hepatitis C treatment and satisfaction with the medical insurance policy for DAA drugs were compared before and after DAA drugs were included in the medical insurance list. RESULTS A total of 203 patients effectively responded among 644 investigated patients. In terms of treatment plans， although there were significant differences in the treatment plan between patients who saw a doctor in 2019 and 2020 （P＜0.05）， the vast majority of patients were cured within the course of treatment （200 cases， 98.52%）， and there were no obvious adverse reactions （193 cases， 95.07%）. In terms of economic burden， the out-of-pocket costs and economic burden of patients treated with DAA drugs in 2020 were significantly lower than those treated with DAA drugs in 2019 （P＜0.05）； in terms of patient services， 78.82% of patients received expert consultation services from designated medical institutions， but 9.85% of patients still did not receive any patient services provided by the hospital. In terms of satisfaction with outpatient reimbursement policy， the overall satisfaction of patients who saw a doctor in 2020 （95.37%） was significantly higher than those who saw a doctor in 2019 （81.05%）（P＜0.05）. CONCLUSIONS The surveyed patients with hepatitis C obtain good efficacy after DAA drugs treatment， and are satisfied with the medical insurance policy of DAA drugs， but the standardized management of patient services in designated medical institutions is insufficient.
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In recent years, with the in-depth study of PD-1 and PD-L1 and the development of immunotherapy, the first problem is how to screen the beneficiaries. Recent clinical studies have shown that the expression level of PD-L1 in circulating tumor cells (CTC) can be used as a potential biomarker to play a guiding role in immunotherapy of malignant tumors. This article reviews the latest clinical research progress on the expression of PD-L1 in circulating tumor cells in various solid tumors.
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Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95%CI) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95%CI) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.
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Adult , Aged , Humans , Male , Middle Aged , Young Adult , Asian People , Biomarkers , C-Reactive Protein/analysis , China/epidemiology , Risk Factors , SeleniumABSTRACT
ObjectiveTo explore whether Hei Xiaoyaosan can inhibit the inflammatory response in the hippocampi of Alzheimer's disease （AD） rats by regulating and activating the Wnt/β-catenin signaling pathway to improve the cognitive and memory dysfunction. MethodAmong the 90 male Wistar rats， 12 were randomly selected as the blank group （normal saline） and 12 as the sham operation group （normal saline）. For the remainder， amyloid β-protein42 （Aβ42） was injected in the left and right hippocampus to induce AD， and then the AD rats were randomized into model group， low-， medium-， and high-dose Hei Xiaoyaosan groups （corresponding doses of Hei Xiaoyaosan， ig）， and donepezil group （donepezil hydrochloride，ig）， with 12 in each group. The administration lasted 42 days. The pathological changes of hippocampal CA1 region was observed based on Nissl staining. The escape latency on the 1st to 5th day in Morris water maze was recorded and the spatial memory on the 6th day was tested. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the expression of interleukin （IL）-6， IL-10， and tumor necrosis factor-α （TNF-α） in rat hippocampus and serum， Western blotting to examine the protein expression of glycogen synthase kinase-3β （GSK-3β）， β-catenin， and peroxisome proliferator-activated receptor gamma （PPARγ）， and real-time polymerase chain reaction （Real-time PCR） to determine the mRNA expression of rat GSK-3β， β-catenin， and PPARγ. ResultCompared with the blank group， the number of neurons in the hippocampal CA1 area of model group was significantly reduced， the arrangement was uneven， the cell body was damaged more obviously， and the Neisser body was unclear. The treatment group was significantly prolonged （P<0.01）， and the number of crossing stations was significantly reduced （P<0.01）， the levels of IL-10 in serum and hippocampus of rats in the model group were significantly decreased， while the levels of IL-6 and TNF-α were significantly increased （P<0.01）， the GSK-3β protein and mRNA in the model group were significantly increased， and the protein expressions of β-catenin and PPARγ were significantly decreased （P<0.01）， and the difference was more obvious. The number of neurons in the donepezil group was more distributed， neatly arranged， the structure was intact， and the Nissl bodies were clear and definite， the escape latency on the 3rd to 5th days in middle and high dose groups of Hei Xiaoyaosan and the donepezil group was significantly shortened （P<0.01）， the number of crossing platforms increased significantly （P<0.01）， the expression levels of IL-10 in the rat hippocampus and serum were significantly increased， while IL-6 and TNF-α were significantly decreased （P<0.01）， GSK-3β in the rat hippocampus was significantly increased. The expressions of GSK-3β protein and mRNA were significantly decreased， while the expression levels of β-catenin and PPARγ protein and mRNA were significantly increased （P<0.01）. There was no significant difference in each index between the donepezil hydrochloride group and the high-dose Hei Xiaoyaosan group. ConclusionHei Xiaoyaosan can inhibit the inflammatory response in the hippocampus of AD rats by regulating the Wnt/β-catenin signaling pathway， thereby alleviating the cognitive and memory impairment of AD rats.
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OBJECTIVE To review economic studies of diabetes drugs in Chinese population systematically ，and to provide reference for promoting the development of pharmacoeconomics research in the field of diabetes and improving the research quality. METHODS Retrieving from PubMed ，Embase，SinoMed，CNKI，Wanfang data ，VIP and other databases ，the literatures on economic evaluation of diabetes drugs in Chinese population were collected ；analysis was carried out on the publication ，research content，study design of the literatures. The Consolidated Health Economic Evaluation Reporting Standards 2013（CHEERS 2013） checklist was used for quality evaluation. RESULTS A total of 380 literatures were included ，involving 348 Chinese literatures and 32 English literatures. The first paper of diabetes drugs in Chinese population was published in 2001. The most evaluated drug was metformin. Most of the studies （79.2％）were conducted by medical institutions ，73.9％ of the studies were short-term economic evaluation，and the methods were mainly cost-effectiveness analysis （61.8％），and most of the studies did not reported clear research perspectives （82.6％）. Evaluated by CHEERS 2013，the average score of included literatures was only 10.57，and 85.8％ of the literatures was of unqualified quality. The average score of Chinese literatures was 10.05，that of English literatures was 16.23，and the reporting quality of English literatures was significantly better than that of Chinese literature s（P＜0.001）. CONCLUSIONS The existing literatures on the economic evaluation of diabetes drugs in Chinese population is of low quality. There are problems such as lack of research perspectives ，single research institution/method ，and non-standard reporting. It is recommended that medical institutions ，universities/research institutions ，enterprises，government and other institutions should strengthen cooperation ，improve their research level ，pay attention to more and newer clinically effective treatment regimens ，and promote the transformation of research results into decision-making evidence.
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OBJECTIVE@#To investigate the significance of peripheral blood lymphocyte to monocyte ratio (LMR) and corrected levels of serum calcium (cCa) as prognostic markers for the newly diagnosed multiple myeloma (MM) patients.@*METHODS@#The clinical data of 114 newly diagnosed MM patients in the Second Affiliated Hospital of Kunming Medical University from January 2013 to March 2020 were retrospectively analyzed. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value, and the patients were divided into high LMR group and low LMR group (LMR≥3.35 and LMR < 3.35). Moreover, the patients were divided into four groups according to initial diagnosis LMR and LMR after four courses of treatment (LMR4): Group A (LMR≥3.35, LMR4≥3.35), Group B (LMR≥3.35, LMR4 < 3.35), Group C (LMR < 3.35, LMR4≥3.35), and group D (LMR < 3.35, LMR4 < 3.35). The simple prognosis model was established by combined with LMR and cCa, the patients were divided into Group a (no risk factor), group b (1 risk factor) and Group c (2 risk factors). Independent sample T-test, Pearson Chi-square test or Mann-Whitney U test were used to evaluate the differences between various parameters, and Kaplan-Meier method and Cox regression were used for survival analysis.@*RESULTS@#The median follow-up time was 13.05（0.1-72.5）months. Survival analysis showed that the patients with low LMR predicted poor prognosis, the overall survival (OS) time of the patients with low LMR was significantly shorter (17 vs 50.5 months, P=0.006) than the patients with high LMR, the difference was also significant between group A and Group D (56.5 vs 30.5 months, P=0.043). The OS of the patients was also significantly shorter in the high cCa group (≥2.75 mmol/L) compared with normal group (8.5 vs 34 months, P=0.006). Multivariate survival analysis showed that LMR < 3.35 (P=0.028) and cCa≥2.75 mmol/L (P=0.036) were the independent risk factors affecting prognosis of MM patients. The comparison of risk factors showed that the median OS of Group a, b and c was 50, 20, and 8.5 months, respectively. The prognosis of the patients without risk factors was better than that of patients with 1-2 risk factors (Group a vs Group b, P < 0.0001; Group a vs Group c, P=0.002).@*CONCLUSION@#LMR and cCa are the independent risk factors affecting the prognosis of newly diagnosed MM patients, and the development of a simple prognosis system combining them can quickly identify the prognosis of newly diagnosed MM patients.
Subject(s)
Humans , Calcium , Lymphocytes , Monocytes , Multiple Myeloma , Prognosis , Retrospective StudiesABSTRACT
At present, there have been many clinical trials and systematic reviews/Meta-analysis proving the good clinical efficacy of Shufeng Jiedu Capsules in the treatment of respiratory diseases, while comprehensive discussion is still required. This article overviews and analyzes the systematic reviews/Meta-analysis of Shufeng Jiedu Capsules to provide evidence support for clinical practice. The systematic reviews/Meta-analysis of Shufeng Jiedu Capsules were searched from CBM, Wanfang, CNKI, VIP, PubMed, EMbase and Cochrane Library. The AMSTAR 2 scale and GRADE system were respectively employed for the evaluation of methodological quality and the grading of evidence quality. Finally, 8 systematic reviews/Meta-analysis published during 2018-2021 were included for analysis. The diseases involved include acute exacerbation of chronic obstructive pulmonary disease, community-acquired pneumonia, acute tonsillitis, acute exacerbation of chronic bronchitis and acute upper respiratory tract infection. The number of included RCTs studies ranged from 8 to 25. The results showed that Shufeng Jiedu Capsules combined with western medicine routine had better therapeutic effect than the latter alone in the treatment of the above five diseases. The reported adverse reactions caused by Shufeng Jiedu Capsules were mainly gastrointestinal discomforts such as mild nausea, diarrhoea and vomiting, with low incidence and mild symptoms, which can be relieved by drug withdrawal. The methodological quality of the included studies was extremely low, and the outcome indicators were mainly of low and very low grades. The efficacy and safety of Shufeng Jiedu Capsules in the clinical treatment of diseases still need to be verified based on more high-quality studies. The relevant clinical research and systematic review/Meta-analysis should pay more attention to methodological quality and reporting standards and strengthen the scientificity of research.
Subject(s)
Capsules , Drugs, Chinese Herbal/therapeutic use , Systematic Reviews as Topic , Treatment OutcomeABSTRACT
Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.