Evaluation on quality of internet-based reporting of COVID-19 in Ningxia, 2020-2021 / 中国热带医学

@#Abstract: Objective　To find out the existing problems and provide reference for further improving the quality of report information by analyzing the report cards of COVID-19 and the positive report cards of primary screening reported in Ningxia. Methods　All COVID-19 case cards from 2020 to 2021 and initial screening positive cards were derived from the Chinese Information System for Disease Control and Prevention according to final review date. The timeliness of case reporting, timeliness of case review, completeness and accuracy of the case cards were analyzed. Results　In Ningxia, the first case of COVID-19 was reported on January 20, 2020, and as of December 31, 2021, 122 confirmed cases and 4 symptomatic infected cases were reported. In 2021, the timely reporting rate of COVID-19 was 98.00%, which increased by 8.24% compared with 2020 (90.54%). Compared with 2020, the average time limit for diagnosis to reporting of COVID-19 in 2021 was shortened by 83.12%; in 2021, the timely review rate of COVID-19 was 100.00%, which increased by 13.84% compared with 2020 (87.84%). Compared with 2020, the time from reporting to final review was shortened by 98.91%. In 2021, the timely rate of positive reports in COVID-19 in Ningxia was 90.00%, among which the timely rate of reports by county (district) nucleic acid detection institutions was the highest (92.31%), followed by municipal (91.67%) and autonomous region (81.82%). Conclusions　At the beginning of the epidemic in 2020, the timeliness of COVID-19 in Ningxia was poor, and through the implementation of measures such as technical training, supervision and inspection to continuously optimize the staffing of medical institutions and disease control institutions, the timeliness of reporting COVID-19 in Ningxia in 2021 was substantially improved, but there were still some weak links. In the future work, technical guidance and training should be carried out for weak links, and efforts should be made to improve the quality of reports.

Improvement of China's legal system for public health emergency management from the perspective of lifecycle management / 中华流行病学杂志

A crucial lesson gained through the pandemic preparedness and response to COVID-19 is that all measures for epidemic control must be law-based. The legal system is related not only to public health emergency management per se but also to all aspects of the institutional supporting system throughout the lifecycle. Based on the lifecycle emergency management model, this article analyses the problems of the current legal system and the potential solutions. It is suggested that the lifecycle emergency management model shall be followed to establish a more comprehensive public health legal system and to gather the intelligence and consensus of experts with different expertise, including epidemiologists, sociologists, economists, jurist and others, which will collaboratively promote the science-based legislation in the field of epidemic preparedness and response for the establishment of a comprehensive legal system for public health emergency management and with Chinese characteristics.

Mechanism of active components of "Notoginseng Radix et Rhizoma-Drynariae Rhizoma" in treatment of osteoporosis based on network pharmacology and in vitro cell experiment / 中国中药杂志

The present study aimed to explore the main active components and potential mechanisms of Panax notoginseng saponins(PNS) and osteopractic total flavone(OTF) in the treatment of osteoporosis(OP) through network pharmacology, molecular docking and in vitro cell experiments, which was expected to provide a theoretical basis for clinical applications. The blood-entering components of PNS and OTF were obtained from literature search and online database, and their potential targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The OP targets were obtained by means of searching Online Mendelian Inheritance in Man(OMIM) and GeneCards. The common targets of the drug and disease were screened by Venn. Cytoscape was used to construct a "drug-component-target-disease" network, and the core components were screened according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened according to the node degree. GO and KEGG enrichment analysis of potential therapeutic targets were carried out by R language. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock Vina. Finally, HIF-1 signaling pathway was selected for in vitro experimental verification according to the results of KEGG pathway analysis. Network pharmacology showed that there were 45 active components such as leachianone A, kurarinone, 20(R)-protopanaxatriol, 20(S)-protopanaxatriol, and kaempferol, and 103 therapeutic targets such as IL6, AKT1, TNF, VEGFA and MAPK3 involved. PI3K-AKT, HIF-1, TNF and other signaling pathways were enriched. Molecular docking revealed that the core components had good binding ability to the core targets. In vitro experiments found that PNS-OTF could up-regulate the mRNA expression levels of HIF-1α, VEGFA and Runx2, indicating that the mechanism of PNS-OTF in treating OP may be related to the activation of HIF-1 signaling pathway, and thus PNS-OTF played a role in promoting angiogenesis and osteogenic differentiation. In conclusion, this study predicted the core targets and pathways of PNS-OTF in treating OP based on network pharmacology and carried out in vitro experimental verification, which reflected the characteristics of multi-component, multi-target and multi-pathway synergy of PNS-OTF, and provided new ideas for the future clinical treatment of OP.

Dryness-alleviating effect of processed Aurantii Fructus from Lingnan based on correlation of fecal metabolomics and dryness / 中国中药杂志

With the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.

Effect of moxibustion on immune function homeostasis in rats with diarrhea irritable bowel syndrome based on SCF/c-kit signaling pathway / 中国针灸

OBJECTIVE@#To observe the effects of moxibustion on the stem cell factor (SCF)/tyrosine kinase receptor (c-kit) signaling pathway and immune function in rats with diarrhea irritable bowel syndrome (IBS-D), and to explore the mechanism of moxibustion for IBS-D.@*METHODS@#Among 52 young rats born from 6 healthy pregnant SPF rats, 12 rats were randomly selected into the normal group, and the remaining 40 rats were treated with the three-factor combination method of maternal separation, acetic acid enema and chronic restraint stress to establish the IBS-D rat model. Thirty-six rats with successful IBS-D model were randomly divided into a model group, a moxibustion group, and a medication group, 12 rats in each group. The rats in the moxibustion group were treated with suspension moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37); the rats in the medication group were treated with intragastric administration of rifaximin suspension (150 mg/kg). All the treatments were given once a day for 7 consecutive days. The body mass, loose stool rate (LSR), the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were measured before acetic acid enema (35 days old), after modeling (45 days old), and after intervention (53 days old). After intervention (53 days old), HE staining was used to observe the morphology of colon tissue, and spleen and thymus coefficients were measured; ELISA method was used to detect serum inflammatory factors (tumor necrosis factor a [TNF-a], interleukin [IL]-10, IL-8), T-lymphocyte subsets (CD+4, CD+8, CD+45), value of CD+4/CD+8 and immune globulin (IgA, IgG, IgM); real-time PCR method and Western blot method was used to detect the expression of SCF, c-kit mRNA and protein in colon tissue; immunofluorescence staining method were used to detect positive expression of SCF and c-kit.@*RESULTS@#After intervention, compared with the normal group, in the model group, the body mass and the minimum volume threshold when AWR scored 3 were decreased (P<0.01), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD+4, CD+45, CD+4/CD+8, IgA, IgG, IgM were increased (P<0.01), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were decreased (P<0.01), and the positive expression of SCF and c-kit was decreased (P<0.01). Compared with the model group, in the moxibustion group and the medication group, the body mass and the minimum volume threshold when AWR scored 3 were increased (P<0.01, P<0.05), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD+4, CD+8, CD+45, CD+4/CD+8, IgA, IgG, IgM were decreased (P<0.01, P<0.05), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were increased (P<0.01), and the positive expression of SCF and c-kit was increased (P<0.01). Compared with the medication group, in the moxibustion group, the level of serum CD+4 was decreased (P<0.05), the value of CD+4/CD+8 was increased (P<0.01), and there was no significant difference in other indexes (P>0.05). The expression of SCF and c-kit mRNA was positively correlated with the minimum volume threshold when AWR scored 3 and IL-10 (P<0.01), and negatively correlated with remaining indexes (P<0.01, P<0.05).@*CONCLUSION@#Moxibustion could reduce visceral hypersensitivity, improve symptoms of abdominal pain and diarrhea in IBS-D rats, and its mechanism may be related to up-regulation of the expression of SCF/c-kit signaling pathway and improvement of IBS-D immune function.

Naringin Inhibits Colorectal Carcinogenesis by Inhibiting Viability of Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To explore the therapeutic effect of naringin on colorectal cancer (CRC) and the related mechanism.@*METHODS@#Cell counting kit-8 (CCK-8) assay and annexin V-FITC/PI assay were used to detect the effect of naringin (50-400 µg/mL) on cell proliferation and apoptosis of CRC cells, respectively. The scratch wound assay and transwell migration assay were used to assess the effect of naringin on CRC cell migration. Four-week-old male nude mice were injected with HCT116 cells subcutaneously to establish the tumor xenograft model. Naringin was injected intraperitoneally at 50 mg/(kg·d), with solvent and 5-fluorouracil treatment as control. The width and length of the tumors were measured and recorded every 6 days, and tumor tissues were photographed and weighed on the last day of the 24-d observation period. Immunohistochemical staining for caspase-3, proliferating cell nuclear antigen and TUNEL assay were used to evaluate the effect of naringin on cell proliferation and apoptosis in tumor tissues. The body weight, food and water intake of mice were recorded, and the major organs in different treatment groups were weighed on the last day and stained with hematoxylin and eosin for histological analysis. Meanwhile, the routine blood indicators were recorded.@*RESULTS@#CCK-8 and annexin V-FITC/PI results confirmed that naringin (100, 200, and 400 µg/mL) could inhibit proliferation and promote apoptosis. The scratch wound assay and transwell migration assay results confirmed the inhibitory activity of naringin against CRC cells migration. In vivo results demonstrated the inhibitory effect of naringin on tumor growth with good bio-compatibility.@*CONCLUSION@#Naringin inhibited colorectal carcinogenesis by inhibiting viability of CRC cells.

Effect of Liangfang Wenjing Decoction on expression of key glycolytic enzymes in uterus and ovaries of rats with coagulating cold and blood stasis syndrome / 中国中药杂志

This study aimed to investigate the relationship between coagulating cold and blood stasis syndrome and glycolysis, and observe the intervention effect of Liangfang Wenjing Decoction(LFWJD) on the expression of key glycolytic enzymes in the uterus and ovaries of rats with coagulating cold and blood stasis. The rat model of coagulating cold and blood stasis syndrome was established by ice-water bath. After modeling, the quantitative scoring of symptoms were performed, and according to the scoring results, the rats were randomly divided into a model group and LFWJD low-, medium-and high-dose groups(4.7, 9.4, 18.8 g·kg~(-1)·d~(-1)), with 10 in each group. Another 10 rats were selected as the blank group. After 4 weeks of continuous administration by gavage, the quantitative scoring of symptoms was repeated. Laser speckle flowgraphy was used to detect the changes of microcirculation in the ears and uterus of rats in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of uterus and ovaries of rats in each group. The mRNA and protein expressions of pyruvate dehydrogenase kinase 1(PDK1), hexokinase 2(HK2) and lactate dehydrogenase A(LDHA) in the uterus and ovaries of rats were examined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. The rats in the model group showed signs of coagulating cold and blood stasis syndrome, such as curl-up, less movement, thickened veins under the tongue, and reduced blood perfusion in the microcirculation of the ears and uterus, and HE staining revealed a thinning of the endometrium with disorganized arrangement of epithelial cells and a decrease in the number of ovarian follicles. Compared with the model group, the treatment groups had alleviated coagulating cold and blood stasis, which was manifested as red tongue, reduced nail swelling, no blood stasis at the tail end as well as increased blood perfusion of the microcirculation in the ears and uterus(P<0.05 or P<0.01). Among the groups, the LFWJD medium-and high-dose groups had the most significant improvement in coagulating cold and blood stasis, with neatly arranged columnar epithelial cells in uterus, and the number of ovarian follicles was higher than that in the model group, especially mature follicles. The mRNA and protein expressions of PDK1, HK2, LDHA in uterus and ovaries were up-regulated in the model group(P<0.05 or P<0.01), while down-regulated in LFWJD medium-and high-dose groups(P<0.05 or P<0.01). The LFWJD low-dose group presented a decrease in the mRNA expressions of PDK1, HK2 and LDHA in uterus and ovaries as well as in the protein expressions of HK2 and LDHA in uterus and HK2 and PDK1 in ovaries(P<0.05 or P<0.01). The therapeutic mechanism of LFWJD against coagulating cold and blood stasis syndrome is related to the down-regulation of key glycolytic enzymes PDK1, HK2 and LDHA, and the inhibition of glycolytic activities in uterus and ovaries.

Systematic review and Meta-analysis of Gusongbao preparation in treatment of primary osteoporosis / 中国中药杂志

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.

Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor / 中国肺癌杂志

BACKGROUND@#The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.@*METHODS@#A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization.@*RESULTS@#There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.@*CONCLUSIONS@#In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.

Anti-inflammation effect of moxibustion for rats with diarrhea-predominant irritable bowel syndrome based on multiple miRNAs regulating NF-κB signal pathway / 中国针灸

OBJECTIVE@#To observe the effect of moxibustion on the regulation of nuclear factor-kappa B (NF-κB) and inflammatory factors by multiple microRNAs (miRNAs) in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), and to explore the anti-inflammatory mechanism of moxibustion on IBS-D.@*METHODS@#Twelve of 52 newborn rats were randomly selected into a normal group. The remaining rats were made into IBS-D model. A total of 36 rats with successful model were randomly divided into a model group, a medication group and a moxibustion group, 12 rats in each group. The rats in the medication group were intraperitoneally injected with pyrrolidine dithiocarbamate (PDTC). The rats in the moxibustion group were treated with moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for 20 min each time. All the intervention was given once a day for 7 days. Before and after modeling as well as after intervention, the body mass, loose stool rate and the minimum volume threshold of abdominal withdrawal reflex (AWR) were measured. After intervention, the contents of serum tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-8 were detected by ELISA method; the morphology of colon tissues was observed by HE staining, and the expressions of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues were detected by real-time PCR. The expressions of NF-κB p65, TNF-α, IL-1β and IL-8 protein in colon tissues were detected by immunofluorescence.@*RESULTS@#After modeling, the body mass and the minimum volume threshold of AWR in the model group were lower than those in the normal group (P<0.01); the rates of loose stool in the model group were higher than those in the normal group (P<0.01); after intervention, in the model group, the inflammatory infiltration of colon tissues was obvious, and the serum levels of TNF-α, IL-1 β, IL-8 were higher than those in the normal group (P<0.05); the expression of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues was higher than that in the normal group (P<0.05); the protein expression of NF-κB p65, TNF-α, IL-1β, IL-8 was also higher than that in the normal group (P<0.01). After intervention, the body mass and the minimum volume threshold of AWR in the medication group and the moxibustion group were both higher than those in the model group (P<0.05); the loose stool rate in the medication group and the moxibustion group were lower than those in model group (P<0.05); the inflammatory cells infiltration in the colon tissues was less, the serum levels of TNF-α, IL-1β and IL-8 as well as the protein expression of NF-κB p65, TNF-α, IL-1β and IL-8 in the colon tissues in the medication group and the moxibustion group were lower than those in the model group (P<0.05, P<0.01). The expression of miR-125b, miR-31, miR-18a and NF-κB p65 mRNA in the medication group were lower than those in the model group (P<0.05). The expression of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in the moxibustion group were lower than those in the model group (P<0.05). The miR-155, miR-125b, miR-29b, miR-31, miR-18a were positively correlated with NF-κB p65 mRNA (0<r<1, P<0.01).@*CONCLUSION@#The anti-inflammatory mechanism of moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for IBS-D rats may be related to regulating multiple miRNAs to inhibit NF-κB signal pathway and reduce the expression of inflammatory factors.

Bibliometric analysis of publications pertaining to artemisinin resistance in Plasmodium falciparum based on Web of Science from 2011 to 2022 / 中国血吸虫病防治杂志

Objective To analyze the global literature output and citation of publications pertaining to artemisinin (ART) resistance in Plasmodium falciparum from 2011 to 2021, so as to provide insights into researches on resistance of P. falciparum to ART. Methods The publications pertaining to ART resistance in P. falciparum were retrieved from the Science Citation Index Expanded (SCIE) database in Web of Science during the period from January 2011 through May 2022. The subject, journal, country, affiliation and author distributions and citations of publications were descriptively analyzed. Results A total of 1 640 publications pertaining to ART resistance in P. falciparum were retrieved in the SCIE database during the period from January 2011 through May 2022, and the number of publications appeared an overall tendency towards a rise during the study period. These articles were published in 343 journals, and the three most productive journals included Malaria Journal (341 publications, 20.79%), Antimicrobial Agents and Chemotherapy (141 publications, 8.60%), American Journal of Aropical Medicine and Hygiene (68 publications, 4.15%), with infectious diseases (565 publications, 34.45%), parasitology (531 publications, 32.38%), and tropical medicine (517 publications, 31.54%) as the predominant subject. The three most productive countries included the United States of America (627 publications, 38.23%), United Kingdom (395 publications, 24.08%), and Thailand (294 publications, 17.94%), with total citations of 25 280, 18 622 and 15 474, respectively, and the most productive countries included Mahidol University (Thailand), Oxford University (England) and London University (England), with 234, 220 publications and 142 publications and 15 058, 15 421 citations and 6 191 citations, respectively. The three most productive authors were all from Mahidol University, with 85, 77 and 63 publications, respectively; and among the three most cited authors, two were from Mahidol University, Thailand, with 8 623 and 7 961 total citations, and one from National Institutes of Health, the United States of America, with 6 267 total citations. A total of 138 articles were published by Chinese scientists, with 3 434 total citations, and National Institute of Parasitic Diseases of Chinese Center for the Diseases Control and Prevention was the most productive Chinese institution, with 35 publications, 1 165 total citations and 33.29 citations per publication. Conclusions The literature output of ART resistance in P. falciparum was relatively high in the United States of America, Europe, and Southeast Asian countries during the period from 2011 to 2021, with a relatively high academic impact. Publications in Malaria Journal and Antimicrobial Agents and Chemotherapy are recommended to be paid much attention by Chinese scientists to understand the latest advances and extend the research interests.

Optimization of Extraction and Purification Process of Total Iridoids and Total Crocins in Gardeniae Fructus / 中国实验方剂学杂志

ObjectiveTo optimize the extraction and purification process of Gardeniae Fructus for industrial production， and to obtain the total iridoid and total crocin extracts. MethodOrthogonal test was used to optimize the water extraction process by taking contents of geniposide， genipin gentiobioside， gardenoside， crocin-1 and crocin-2 as indicators and the decocting time， decocting times and water amount as factors. The purification process was optimized by single factor test， and four different types of macroporous adsorption resins were screened. The process conditions such as resin type， maximum loading amount， water washing amount， ethanol concentration， ethanol dosage， and flow rate of sample loading were mainly investigated. In addition， the drying methods （vacuum drying and spray drying） of the extract were investigated， and a pilot scale-up verification test was carried out. ResultThe optimal water extraction process of Gardeniae Fructus was to add 15， 10 times the amount of water for decocting twice， 1 h each time. The optimal purification process was as follows：the water extract through SP825L macroporous resin column， the amount of crude drug-the amount of resin （1∶1.5）， the sample loading flow rate of 3 BV h-1， adding 2 BV of water to remove impurities， adding 4 BV of 30% ethanol to obtain the iridoid part， then adding 3 BV of 70% ethanol to obtain the crocin part， collecting the ethanol lotion， and drying at 70 ℃. Under these conditions， the extraction amount of total iridoids was 590.75 mg·g-1 with the transfer rate of 70.48%， and the yield of dry extract was 8.89%. The extraction amount of total crocins was 83.37 mg·g-1 with the transfer rate of 22.20%， and the dry extract yield was 2.60%. ConclusionThe optimized extraction and purification process is stable and feasible with high extraction rate of active components， which is suitable for the industrial extraction and purification of active parts of Gardeniae Fructus.

Sequential Treatment with Syndrome Differentiation on Children's Refractory Nephrotic Syndrome with Yiqi Huayu Qingre Prescription / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy of sequential syndrome differentiation of Yiqi Huayu Qingre prescription （YHQ） in the treatment of refractory nephrotic syndrome in children. MethodA total of 112 children with refractory nephrotic syndrome were randomly divided into an observation group （57 cases） and a control group（55 cases）. The children in the control group were treated with prednisone tablets combined with tacrolimus，and those in the observation group were treated with YHQ by sequential syndrome differentiation on the basis of the control group. The total effective rates of the two groups after treatment were observed. The 24-hour urinary total protein（24 h UTP），plasma albumin（ALB），cholesterol（CHO），triglycerides（TG）， and traditional Chinese medicine quality of life scale scores before treatment and after four weeks，eight weeks，16 weeks，24 weeks，32 weeks，40 weeks，and 52 weeks in the two groups were recorded. The total course of treatment and the total accumulation of hormones were compared among the children with reduced or no hormone treatment till 52 weeks during treatment. ResultThe total effective rate in the observation group was higher （Z=-2.052，P<0.05）. The observation group had lower 24 h UTP and higher ALB at each follow-up time point than the control group（P<0.05，P<0.01）. At four weeks，eight weeks，and 16 weeks of treatment，there was no statistically significant difference in CHO between the observation group and the control group，and the observation group was lower than the control group in CHO at the rest of the time points （P<0.05，P<0.01）. For TG， the observation group was not significantly different from the control group at four weeks，eight weeks，16 weeks，and 40 weeks of treatment，but lower at 24，32，and 52 weeks （P<0.05，P<0.01）. The total treatment course of hormones in the observation group was shorter（P<0.01）， with less total accumulation（P<0.01）. At different follow-up time points，the total score of traditional Chinese medicine quality of life scale in the observation group was superior to that in the control group（P<0.05，P<0.01），and the scores of the observation group in the four dimensions （physiological function，independent factor，social factor，and psychological factor） after treatment were higher than those in the control group（P<0.05，P<0.01）. ConclusionYHQ under sequential syndrome differentiation has a definite clinical effect in treating children with refractory nephrotic syndrome. It has advantages in shortening the total course of hormone treatment and reducing the total accumulation of hormones，and can improve the quality of life of children with refractory nephrotic syndrome.

Regulation of Wenjingtang on HIF-1α Expression and Mitochondrial Function of Ectopic Endometrial Stromal Cells in Patients with Endometriosis / 中国实验方剂学杂志

ObjectiveThis study investigated the mechanism of Wenjingtang in the prevention and treatment of endometriosis （EMT） from the perspective of regulating hypoxia stress and mitochondrial function. MethodPrimary human endometrial stromal cells （ESCs） form ectopic endometrial tissues were isolated and cultured， the cells were divided into control group （Control）， 5% control serum group （5% KBXQ）， 10% control serum group （10% KBXQ）， 5% Wenjingtang serum group （5% WJTXQ） and 10% Wenjingtang serum group （10% WJTXQ）. ESCs in different groups were detected for proliferation by methyl thiazolyl tetrazolium （MTT） assay， mRNA and protein expression of hypoxia inducible factor-1α （HIF-1α） by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analysis， mitochondrial ultrastructure by transmission electron microscope， mitochondrial function ［mitochondrial membrane potential， mitochondrial membrane potential（MMP） and cytochrome C（Cyt C） content］ and apoptosis （cell membrane permeability， nuclear fluorescence intensity， nuclear size and cell counts） by high content screening （HCS） assay， apoptosis rate by flow cytometry， and proteins of B-cell lymphoma-2 （Bcl-2） associated X （Bax）， Bcl-2 and cleaved cysteinyl aspartate specific proteinase-3 （cleaved Caspase-3） by Western blot. ResultCompared with Control group， the 5% KBXQ and 10% KBXQ groups showed increased cell viability （P<0.01）， there was no significant change in HIF-1α mRNA and protein expression， transmission electron microscopy showed that the mitochondrial cristae were obvious and the inner and outer membranes of mitochondria were clear， HCS multichannel fluorescence staining showed that there were no significant changes in the expression of MMP， Cyt C and cell membrane permeability， and the nuclei showed uniform light staining， there were no significant changes in apoptosis rate， cleaved Caspase-3 protein expression and Bax/Bcl-2 ratio. Compared with Control group and corresponding concentration KBXQ group， the 5% WJTXQ and 10% WJTXQ group showed decreased cell viability （P<0.01） and HIF-1α mRNA and protein levels （P<0.05，P<0.01）， the ultrastructure of mitochondria was destroyed， some mitochondria were swollen and the cristae were blurred， moreover， decreased MMP and up-regulated Cyt C release （P<0.05，P<0.01）， increased cell membrane permeability （P<0.01）， and apoptosis characteristics included nuclear pyknosis， DNA agglutination in nucleus and decrease of cell numbers were observed （P<0.05，P<0.01）， increased apoptosis rate （P<0.01）， which was consistent with the results of HCS analysis， and up-regulated expression levels of cleaved Caspase-3 protein and Bax/Bcl-2 ratio （P<0.05，P<0.01）. ConclusionIn conclusion， the results suggest that Wenjingtang can improve hypoxia stress via down-regulating HIF-1α expression in ectopic ESCs， and inhibit cell proliferation， reduce mitochondrial biological activity and induce apoptosis， which might be the internal mechanism of Wenjingtang in preventing and treating EMT.

Medicinal Textual Research of Tsaoko Fructus / 中国实验方剂学杂志

Tsaoko Fructus is a type of food with the homology of medicine and food，and has a long history of cultivation and application in China. With the deepening of the development and utilization of Tsaoko Fructus，its economic value has appeared obviously，and relevant industries have great potential，with an important role in poverty alleviation in mountainous areas. However，the plants source of Tsaoko Fructus are confused in the process of actual production and resource utilization，and there is a lack of systematic report about the origin of varieties and medicinal history. The paper focused on a textual research for its names，plant sources，changes of the genuine producing areas and traditional efficacy through consulting the herbal works and the analysis of modern literature. The results showed that the medicine of Tsaoko Fructus was first recorded in ancient literatures of the Song dynasty，and there were many aliases and synonyms of the herb， with a great difference between ancient and modern times. In modern records，the medicinal alias names such as Hongcaoguo，Tucaoguo，Caoguoren are similar with the Chinese name of Caoguo，but they are not the same kind of plant and shall be distinguished. In the Ming dynasty，variety and source of the herb was complicated，and it was often recorded as the same class of medicinal materials with Amomi Fructus Rotundus and Alpiniae Katsumadai Semen，until it was listed as a class of medicinal material and distinguished from confounding medicines in the Qing Dynasty. The prescriptions containing Tsaoko Fructus include Caoguoyin，Caoguosan，Caoguowan，Caoguoshushui. Tsaoko Fructus could be used as medicine with peel or only kernel according to different diseases，and mainly processed with water or wine. In addition，there are other processing methods，such as frying，salt-processing， ginger- processing，simmering flour. Ancient literatures have basically the same records on properties，efficacies and indications of Tsaoko Fructus，considering it was warm in nature with the effect in relieving vomiting，eliminating food，intercepting malaria，expelling phlegm. This study provided a theoretical basis for its origin，quality control and resource development and utilization.

Analysis and Identification of Chemical Constituents in Hypoglycemic Effective Fractions of Longan Folium Based on UPLC-Q-Orbitrap HRMS / 中国实验方剂学杂志

Objective:Chemical constituents in hypoglycemic effective fractions of Longan Folium were isolated and identified by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） to clarify the hypoglycemic substance basis of Longan Folium. Method:Chemical constituents in hypoglycemic effective fractions of Longan Folium were isolated on a Thermo Hypersil GOLD C₁₈ column （2.1 mm×100 mm， 1.9 μm）， the mobile phase was 0.1% formic acid acetonitrile solution and 0.1% formic acid solution （containing and 10 mmol ammonium acetate） for gradient elution. HRMS was operated in the positive and negative ion modes with the scanning range of <italic>m</italic>/<italic>z</italic> 100-1 500. Result:The secondary fragment ion information of target compounds was selected and compared with the compounds reported in the databases and related literature to further confirm these compounds. Nine compounds were identified in the ethanol fraction of Longan Folium， including cynaroside， kaempferol， quercitrin， luteolin， shikimic acid， citric acid， <italic>L</italic>-tyrosine， adenosine and nicotinamide. A total of 11 compounds were determined in the ethyl acetate fraction （cynaroside， quercitrin， kaempferol， luteolin， shikimic acid， gallic acid， protocatechuic acid， adenosine， nicotinamide， <italic>L</italic>-phenylalanine and scopoletin）， and 10 compounds were identified in the <italic>n</italic>-butanol fraction （cynaroside， kaempferol-3-<italic>O</italic>-rutinoside， kaempferol， astragalin， luteolin， citric acid， gallic acid， adenosine， nicotinamide and 5-hydroxymethylfurfural）. And five common compounds were identified in these three hypoglycemic effective fractions. Conclusion:The established UPLC-Q-Orbitrap HRMS can quickly identify chemical constituents in three hypoglycemic effective fractions of Longan Folium， their main chemical constituents are flavonoids and their glycosides， organic acids and nitrogen-containing compounds， which provides technical support and scientific evidence for the study on pharmacodynamic material basis and quality control of Longan Folium.

Research Status of Zexietang / 中国实验方剂学杂志

Zexietang is derived from Jingui Yaolue （《金匮要略》）， which is composed of Alismatis Rhizoma and Atractylodis Macrocephalae Rhizoma， and has the effect of inducing diuresis and invigorating the spleen to produce water. Compared with western medicine in the treatment of related diseases， Zexietang can not only improve the curative effect， but also reduce the occurrence of adverse reactions， so as to achieve long-term stable administration. The authors sorted out and analyzed the chemical composition， pharmacological effect and clinical application of Zexietang in recent years. It was found that the main active components of Zexietang were alismol A and B， 23-acetyl-alismol B and C， atractylenolides （atractylenolide Ⅰ， Ⅱ， Ⅲ） and polysaccharides. Pharmacological experiments showed that they had diuretic， hypolipidemic， anti-inflammatory and others. And it can be used in the treatment of hypertension， hyperlipidemia， vertigo， cerebral vascular insufficiency and other diseases combined with other Chinese materia medica， and the curative effect is obvious. By summarizing the research status of Zexietang in recent years， its active components and pharmacological mechanism can be further clarified， which provides the basis for the clinical application of Zexietang and guides the direction of its further research.

Research Progress of Targeted Drug Delivery Nanocarriers Through Blood-brain Barrier / 中国实验方剂学杂志

The small size， moderate drug loading， and targeting properties of nano-preparations make them can be excellent delivery tools for drugs， genes or proteins crossing the cell or blood-brain barrier （BBB）. Currently， facilitating drug crossing BBB with innovative nano-drug delivery systems is considered as a strategic approach for the prevention， diagnosis and treatment of central nervous system （CNS） diseases. However， with the deepening of the research， the adverse reactions and toxicity of nanocarriers have gradually attracted the attention of researchers. Based on this， this paper summarized the situation of BBB-penetrating targeted nano-preparations at home and abroad in recent years from the perspective of classification of types and properties of nanocarriers， and analyzed the advantages and disadvantages of each carrier. The results showed that nano-preparations with active ingredients of traditional Chinese medicine （TCM） as carriers have become a promising way of cancer treatment， but the complexity and diversity of TCM components limited its application to a certain extent. Further studies should be strengthened to lay a foundation for the application and development of TCM nano-preparations in the field of CNS diseases.

Herbal Textual Research on Polygonati Rhizoma and Ethnic Usage / 中国实验方剂学杂志

Polygonati Rhizoma was first recorded in Mingyi Bielu（《名医别录》） as both medicine and food due to its high edible and medicinal values.However，there is no systematic textual research on its use as medicine and food. Polygonati Rhizoma and Polygonati Odorati Rhizoma show similar morphology，so they are often confused.Clematis apiifolia and Polygonatum odoratum are often regarded as the original plants of Polygonati Odorati Rhizoma. By reviewing the related records in Chinese herbal books of the past dynasties，this paper aimed to clarify the relationship between Polygonati Rhizoma，C.apiifolia and P.odoratum，trace the historical evolution of Polygonati Rhizoma as medicine and food from the name，harvesting and processing，property，flavor and meridian tropism，efficacy and indications，edible and medicinal records，and contraindications，and summarize its application in ethnic medicine，in order to inherit and develop the ethnic medicine. The findings demonstrated that the name of Polygonati Rhizoma and its synonyms were derived from its pictogram，function，and place of origin，containing a wealth of myth implication and Taoism thought.Polygonati Rhizoma，C.apiifolia and P.odoratum are three species，different from the conclusions in previous textual research. The seedlings，flowers，seeds，and rhizomes of Polygonati Rhizoma all could be used for edible and medicinal purposes，with its edible records exceeding the medicinal records. There were 22 medical books from the ethnic minority groups such as The Annals of National Medicine in Yunnan，Zhongguo Minzu Yaozhi Yao，and Dictionary of Chinese Ethnic Medicine recording the knowledge and application of 12 species in Polygonatum by 26 ethnic minorities.Due to their different living environments，lifestyles，and cultural customs，ethnic minorities have formed their unique medical cultures.

Shexiang Tongxin Dropping Pill () Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STDP) following sodium laurate-induced coronary microembolization (CME) in rats.@*METHODS@#Forty rats were divided into 4 groups: the control (sham) group, CME group, low-dose STDP pretreatment group (20 mg·kg@*RESULTS@#The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers (superoxide dismutase and catalase, P<0.01 for all). In contrast, the rats in the low- and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi (P<0.05); moreover, STDP restored the antioxidant-related protein activities and mitochondrial function, inhibited mPTP opening, decreased AKT-Ser473 phosphorylation, and increased GSK3β-Ser9 phosphorylation (P<0.05 or P<0.01).@*CONCLUSION@#STDP may be useful for treatment of CME, possibly via regulation of mPTP opening and AKT/GSK3β phosphorylation.