Benzyl isothiocyanate induces cell cycle arrest and apoptosis in cervical cancer through activation of p53 and AMPK-FOXO1a signaling pathways / 中国药理学通报

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interfere with 5-HT Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms.@*METHODS@#Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05).@*CONCLUSION@#EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.

Review of constructing animal models of depression after myocardial infarction / 中国药理学通报

The incidence of depression after myocardial infarction (DAMI) is high, causing significant harm to the patients' physical and mental health, but the pathogenesis is unknown. Establishing animal models which simulate the pathogenesis of DAMI in humans is an effective way to explore the mechanism of the disease. In this paper, problems existing in the modeling process, such as animal selection, model selection, model preparation and behavioral evaluation, are summarized and considered in order to provide reference for DAMI model research.

Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia / 中华血液学杂志

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

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.

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.

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.

Study on the mechanism of haitongpi prescription extract ointment in the treatment of knee osteoarthritis based on transcriptome / 中国骨伤

OBJECTIVE@#To explore the mechanism of Haitongpi Prescription extract in the treatment of knee osteoarthritis based on transcriptome.@*METHODS@#Total of 12 SPF grade rats were divided into control group(group C), model group(group M), and Haitongpi prescription group(group HP). The knee osteoarthritis rat model was established using the Panicker method for group M and group HP, and group HP was intervened by local topical application of Haitongpi Prescription extract for 4 weeks. Total RNA from mouse knee cartilage was extracted and three sets of differential genes were obtained through sequencing.Differential genes were prediction and analysis through GO function and KEGG pathway enrichment analysis.@*RESULTS@#A total of 109 differentially expressed genes were identified in Group C versus Group M, while 118 differentially expressed genes were identified in Group M versus Group HP, resulting in a total of 28 genes. GO functional enrichment analysis showed that the mechanism of HP extract in treating knee osteoarthritis mainly involved immunoglobulin mediated immune response, immunoglobulin complexes, and antigen binding; KEGG pathway enrichment analysis showed correlation with tumor necrosis factor (TNF) signaling pathway, interleukin 17(IL-17) signaling pathway, and estrogen signaling pathway.@*CONCLUSION@#HP extract can exert therapeutic effects on knee osteoarthritis through mechanisms such as immunoglobulin mediated immune response, immunoglobulin complexes, and antigen binding, as well as signaling pathways such as TNF signaling pathway, IL-17 signaling pathway, and estrogen signaling pathway.

Free posterior interosseous artery perforator flap in the treatment of finger with skin and soft tissue defect / 中国骨伤

OBJECTIVE@#To explore clinical effects of repairing skin and soft tissue defect of finger with free posterior interosseous artery perforator flap.@*METHODS@#Totally 8 patients with finger skin and soft tissue defect repaired with free posterior interosseous artery perforator flap were treated from May 2021 to November 2022, including 7 males and 1 female aged from 24 to 54 years old, and soft tissue defect area ranged from 3.0 cm×1.5 cm to 5.0 cm×3.0 cm. The time from injury to flap repair ranged from 3 to 83 h. The free posterior interosseous artery perforator flap was applied to repair finger defect, the area of the flap ranged from 3.5 cm×2.0 cm to 5.2 cm×3.5 cm, the donor area of flap was sutured directly. The survival, appearance, texture and donor complications of the flap were observed after operation, and Dargan functional standard was used to evaluate clinical effect of finger function.@*RESULTS@#All flap of 8 patients were survived, and followed up from 3 to 12 months. There was no obvious swelling, soft texture, obvious pigmentation, linear intaglio in donor area only, and without obvious complications were found. Among them, 3 patients'skin flaps were repaired for the defect of palm of the fingers, and sensory recovery was good, two-point discrimination ranged from 5 to 9 mm. According to Dargan functional evaluation, 3 patients excellent, and 5 good.@*CONCLUSION@#Free posterior interosseous artery perforation branch flap could be used to repair the defect of finger. The thickness of flap is moderate, operation is convenient, appearance and texture of the operative flap are good, and the donor site is small without obvious complications, and obtain satisfactory clinical effect.

Establishment of a quantitative method for GC analysis of polyoxyethylene (35) castor oil in microemulsion extracts / 中国中药杂志

With the continuous exploration of microemulsions as solvents for traditional Chinese medicine extraction, polyoxyethy-lene(35) castor oil(CrEL), a commonly used surfactant, is being utilized by researchers. However, the problem of detecting residues of this surfactant in microemulsion extracts has greatly hampered the further development of microemulsion solvents. Based on the chemical structures of the components in CrEL and the content determination method of castor oil in the 2020 edition of the Chinese Pharmacopoeia(Vol. Ⅳ), this study employed gas chromatography(GC) and single-factor experiments to optimize the preparation method of methyl ricinoleate from CrEL. The conversion coefficient between the two was validated, and the optimal sample preparation method was used to process microemulsion extracts of Zexie Decoction from three batches. The content of methyl ricinoleate generated was determined, and the content of CrEL in the microemulsion extracts of Zexie Decoction was calculated using the above conversion coefficient. The results showed that the optimal preparation method for CrEL was determined. Specifically, 10 mL of 1 mol·L~(-1) KOH-methanol solution was heated at 60 ℃ for 15 min in a water bath. Subsequently, 10 mL of boron trifluoride etherate-methanol(1∶3) solution was heated at 60 ℃ for 15 min in a water bath, followed by extraction with n-hexane twice. CrEL could stably produce 20.84% methyl ricinoleate. According to this conversion coefficient, the average mass concentration of CrEL in the three batches of Zexie Decoction microemulsion extracts was 11.94 mg·mL~(-1), which was not significantly different from the CrEL mass concentration of 11.57 mg·mL~(-1) during microemulsion formulation, indicating that the established content determination method of this study was highly accurate, sensitive, and repeatable. It can be used for subsequent research on microemulsion extracts of Zexie Decoction and provide a reference for quality control of other drug formulations containing CrEL.

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.

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.

Effect of short hairpin RNA lentivirus-mediated silencing of pleomorphic adenoma gene like-2 on proliferation, migration and invasion of hepatocellular carcinoma cells / 解剖学报

Objective To investigate the effect of short hairpin RNA(shRNA)-mediated pleomorphic adenoma gene like-2 (PALAG2) silencing on the malignant behavior of hepatocellular carcinoma cells and its mechanism. Methods Real-time PCR and Western blotting were used to detect the expression level of PLAGL2 in liver cancer tissues and adjacent tissues. Hepatoma cells MHCC97-L were cultured in vitro, the lentiviral vector plasmid PLAGL2-shRNA and control NC-shRNA were constructed, transfected into MHCC97-L cells, and stable transfected strains were selected with puromycin. CCK-8 and Transwell chamber assay detected the proliferation activity and the number of migration and invasion of MHCC97-L cells after silencing PLAGL2. Western blotting was used to detect the expression of p-PI3K and p-Akt proteins. The PI3K/ Akt signaling pathway activator was used to treat MHCC97-L cells to detect cell proliferation, migration and invasion. Results The expression of PLAGL2 was significantly increased in liver cancer tissue (P < 0. 05). Transfection of 9 strains of MHCC97-L cells with PLAGL2-shRNA could significantly reduce the expression level of PLAGL2, and the ability of proliferation, migration, and invasion of MHCC97-L cells was also weakened (P<0. 05), and the expression levels of p-PI3K, and p-Akt were inhibited (P<0. 05), PI3K/ Akt activator could obviously reverse the above phenomenon. Conclusion shRNA lentiviral vector pathway can effectively silence the expression of PLAGL2 gene in hepatocarcinoma cells. Silencing of PLAGL2 can significantly inhibit the malignant behavior of proliferation, migration and invasion of hepatocarcinoma cells, and its mechanism may be related to the inhibition of PI3K / Akt signaling pathway activation.

Research progress on hypoxia-induced imbalance of calcium homeostasis in pulmonary artery smooth muscle cells and its treatment / 中国药理学通报

Chronic hypoxic lung diseases are major causes of disability and mortality worldwide, which are typically aggravated by hypoxic pulmonary hypertension.The pathogenesis of hypoxic pulmonary hypertension is complex, and its mechanism has not been fully elucidated.The previous studies have shown abnormally elevated levels of free Ca + in the cytoplasm of pulmonary artery smooth muscle cells to be the predominant drivers of pulmonary hypertension , causing continuous contraction and remodeling of the pulmonary vessels.This article briefly summarizes the mechanism of hypoxia-induced imbalance in calcium homeostasis in pulmonary artery smooth muscle cells, together with its related drug research, based on the existing literature.Hypoxia induces an imbalance in calcium homeostasis in pulmonary artery smooth muscle cells by regulating hypoxia-inducible factor-1, K+ , store-operated calcium channel, receptor-operated calcium channel, the Ca +-sensing myosin contractile mechanism by binding to calmodulin, leading to pulmonary vasoconstriction.Ca + can also activate PKC/ MAPKs and PI3K/Akt/mTOR pathways, leading to pulmonary vascular remodeling.

Research progress on therapeutic strategies for improving pulmonary vascular remodeling in pulmonary hypertension / 中国药理学通报

Pulmonary hypertension(PH)is a chronic,progressive,high-mortality disease characterized by a continuous increase in pulmonary vascular pressure. All types of PH have the same characteristics,i.e.,the excessive proliferation,anti-apoptosis and inflammation of pulmonary artery endothelial cells and smooth muscle cells,which leads to progressive thickening of pulmonary small vessels,resulting in pulmonary vascular remodeling and increased pulmonary vascular resistance,ultimately leading to right ventricular hypertrophy,heart failure,and death. The drugs used to treat PH mainly include L-type calcium channel blockers,phosphodiesterase 5 inhibitors,guanosine cyclase activators,endothelin receptor antagonists,and synthetic prostacyclin and its analogues. These drugs reduce pulmonary artery pressure by relaxing pulmonary blood vessels but do not cure the patient,and their prognosis remains poor. Therefore,the development of drugs that can effectively improve or even reverse pulmonary vascular remodeling is the key to treating PH. In recent years,studies on pulmonary vascular remodeling mainly included(1)the synthesis of new small-molecule compounds;(2)the transformation of mature drugs,such as the use of drug combinations and dosage form transformation,etc.;(3)the pharmacodynamic evaluation of traditional Chinese medicines and derived compounds based on the theory of "lung distension";(4)research into monomers of traditional Chinese medicine; and(5)research into new targets.

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.