Long non-coding RNA alpha-2-macroglobulin antisense RNA 1 regulating oxidized low density lipoprotein-induced human brain microvascular endothelial cell damage by targeting microRNA-106b-5p / 解剖学报

Objective To investigate the effect of long non-coding RNA (lncRNA) alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) targeting microRNA (miR) -106b-5p on oxidized low-density lipoprotein (ox-LDL) -induced injury of human brain microvascular endothelial cells. Methods Human brain microvascular endothelial cells (ox-LDL group) were induced by ox-LDL, normal cultured cells were control group (Ctrl); A2M-AS1 overexpression (pcDNAA2M-AS1 group), empty vector (pcDNA group), miR-106b-5p inhibitor (anti-miR-106b-5p group), negative control (anti-miR-NC group), pcDNA-A2M-AS1 with control mimic NC (miR-NC group), pcDNA-A2M-AS1 with miR-106b-5p mimic (miR-106b-5p mimics group) were transfected into cells and treated with ox-LDL, n = 9. Real-time PCR was used to detect the expression levels of A2M-AS1 and miR-106b-5p; Kits were used to detect malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)); Flow cytometry and TUNEL detected apoptosis; Dual luciferase reporter gene assay detected A2M-AS1 and miR-106b-5p targeting; Western blotting detected Bcl-2 and Bax protein expression. Results Compared with the Ctrl group, the expression level of A2M-AS1 in the ox-LDL group decreased, and the activity of SOD and CAT and the protein level of Bcl-2 decreased (P<0.05), while the expression level of miR-106b-5p and the level of MDA increased (P<0.05), and the rate of apoptosis and the protein level of Bax increased (P<0.05). Overexpressing A2M-AS1 or interfering with miR-106b-5p decreased the MDA level, apoptosis rate and Bax protein level after ox-LDL-induced cells, and increased SOD, CAT activity and Bcl-2 protein level (P<0.05). A2M-AS1 targeted miR-106b-5p; upregulation of miR-106b-5p reversed the effect of overexpressed lncRNA A2M-AS1 on ox-LDL-induced injury of human brain microvascular endothelial cells (P < 0.05). Conclusion A2M-AS1 attenuates ox-LDL-induced injury of human brain microvascular endothelial cells by targeting miR-106b-5p.

Pharmacoeconomic evaluation of sugemalimab consolidation therapy for stage Ⅲ non-small cell lung cancer / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of sugemalimab in patients with stage Ⅲ non-small cell lung cancer （NSCLC） whose disease had not progressed after concurrent or sequential chemoradiotherapy from the perspective of the Chinese healthcare system. METHODS Based on the GEMSTONE-301 clinical trial，a three-health state partitioned survival model （PartSA） was developed to simulate the progression of disease，with model cycle of 3 weeks and a lifetime time range； the main output indicators of the model were total cost，quality-adjusted life year （QALY），and incremental cost-effectiveness ratio （ICER）； the cost and health output were discounted using 5% discount rate. Using 1-3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay （WTP） threshold，the cost-utility analysis method was used for analysis，and sensitivity analysis and scenario analysis were conducted to assess model robustness. RESULTS Compared with placebo，ICER for sugemalimab consolidation therapy was 59 872.57 yuan/QALY，which was less than one time China’s per capita GDP in 2022 （85 698 yuan） as the WTP threshold. The scenario analysis results further confirmed the robustness of the model. The results of single factor sensitivity analysis indicated that the cost of drugs （pembrolizumab，sugemalimab，docetaxel） and the utility value of disease progression status had a significant impact on ICER； the results of the probabilistic sensitivity analysis showed that sugemalimab had 67.2% probability of being cost-effective at one time China’s GDP per capita in 2022 as the WTP threshold； when 20 000 yuan （less than 3 times GDP per capita in China of 257 094 yuan） was used as the WTP threshold，the probability of sugemalimab consolidation therapy being cost-effective was greater than 98%. CONCLUSIONS The consolidation therapy with sugemalimab is cost-effective for stage Ⅲ NSCLC whose disease had not progressed after concurrent or sequential chemoradiotherapy.

Comparison of three methods for establishing rat peri-implantitis model / 北京大学学报(医学版)

OBJECTIVE@#To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods.@*METHODS@#Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1β (IL-1β). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death.@*RESULTS@#After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1β in the test groups were higher than those in the control group (P < 0.05).@*CONCLUSION@#Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.

Bioinformatics analysis and validation of key genes in transformation of idiopathic membranous nephropathy to end-stage renal disease and traditional Chinese medicines for prevention and treatment / 中国中药杂志

This study used bioinformatics analysis to screen out key genes involved in the transformation of idiopathic membranous nephropathy to end-stage renal disease and to predict targeted Chinese herbs and medicines and active ingredients with preventive and curative effects. The GSE108113 microarray of idiopathic membranous nephropathy and GSE37171 microarray of were downloaded from the comprehensive gene expression database, and 8 homozygous differentially expressed genes for the transformation of idiopathic membranous nephropathy into end-stage renal disease of were screened out by R software. GraphPad Prism was used to verify the expression of homozygous differentially expressed genes in GSE115857 microarray of idiopathic membranous nephropathy and GSE66494 microarray of chronic kidney disease, and 7 key genes(FOS, OGT, CLK1, TIA1, TTC14, CHORDC1, and ANKRD36B) were finally obtained. The Gene Ontology(GO) analysis was performed. There were 209 functions of encoded proteins, mainly involved in regulation of RNA splicing, cytoplasmic stress granule, poly(A) binding, etc. Thirteen traditional Chinese medicines with the effect of preventing the transformation of idiopathic membranous nephropathy to end-stage renal disease were screened out from Coremine Medical database, including Ginseng Radix et Rhizoma, Lycopi Herba, and Gardeniae Fructus, which were included in the Chinese Pharmacopoeia(2020 edition). The active ingredient quercetin mined from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) had ability to dock with the key gene FOS-encoded protein molecule, which provided targets and research ideas for the development of new traditional Chinese medicines.

Effects of mild/asymptomatic COVID-19 on semen parameters and sex-related hormone levels in men: a systematic review and meta-analysis / 亚洲男科学杂志(英文版)

Coronavirus disease 2019 (COVID-19) has yet to be proven to alter male reproductive function, particularly in the majority of mild/asymptomatic patients. The purpose of this study was to explore whether mild/asymptomatic COVID-19 affects semen quality and sex-related hormone levels. To find suitable comparative studies, a systematic review and meta-analysis was done up to January 22, 2022, by using multiple databases (Web of Science, PubMed, and Embase). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify and choose the studies. Meta-analysis was used to examine the semen parameters and sex-related hormones of mild/asymptomatic COVID-19 patients before and after infection. The effects of semen collection time, fever, and intensity of verification on semen following infection were also investigated. A total of 13 studies (n = 770) were included in the analysis, including three case-control studies, six pre-post studies, and four single-arm studies. A meta-analysis of five pre-post studies showed that after infection with COVID-19, sperm concentration (I2 = 0; P = 0.003), total sperm count (I2 = 46.3%; P = 0.043), progressive motility (I2 = 50.0%; P < 0.001), total sperm motility (I2 = 76.1%; P = 0.047), and normal sperm morphology (I2 = 0; P = 0.001) decreased. Simultaneously, a systematic review of 13 studies found a significant relationship between semen collection time after infection, inflammation severity, and semen parameter values, with fever having only bearing on semen concentration. Furthermore, there was no significant difference in sex-related hormone levels before and after infection in mild/asymptomatic patients. Mild/asymptomatic COVID-19 infection had a significant effect on semen quality in the short term. It is recommended to avoid initiating a pregnancy during this period of time.

Altered microRNA expression profiles of human spermatozoa in normal fertile men of different ages / 亚洲男科学杂志(英文版)

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.

Clinical Comprehensive Evaluation of Jintiange Capsules in Treatment of Osteoporosis / 中国实验方剂学杂志

ObjectiveTo comprehensively evaluate the clinical value of Jintiange Capsules （JCs） in the treatment of osteoporosis （OP） and clarify the intrinsic advantages and clinical treatment characteristics of JCs， providing references for relevant departments of national health and medicine decision-making and the basis and clues for clinical and basic in-depth research. MethodBased on evidence-based medical evidence， this study integrated quantitative and qualitative methods and combined with questionnaires， official website data， human experience， pharmacoeconomic evaluation， and other research methods. From the effectiveness， safety， economy， innovation， suitability， accessibility， and traditional Chinese medicine （TCM） characteristics of the '6+1' dimension， the clinical evidence and value of JCs in the treatment of OP were comprehensively evaluated， forming the 'clinical evidence and value evaluation index'. The comprehensive evaluation of clinical value was based on the multi-criteria decision analysis framework. The expert meeting method was used to empower each dimension and value index. The clinical evidence and value evaluation software of Chinese patent medicine （CSC v2.0） was used to calculate the total value score， and the clinical advantages of JCs were comprehensively evaluated. ResultBased on randomized controlled clinical studies and systematic review， data analysis of spontaneous reporting system （SRS）， case reports， non-clinical safety studies， etc.， serious adverse drug reactions （ADRs） were reported after the launch of this product monitored by SRS， mainly involving abnormal liver function and adverse reactions of cardiovascular system. Therefore， the safety evidence adequacy of this product should be further improved， and the safety evaluation was Grade B. Meta-analysis showed that JCs were superior to the control group in improving the total clinical effective rate， improving bone mineral density， reducing visual analogue scale （VAS） score， and shortening fracture healing time. Combined with Grading of Recommendations Assessment， Development and Evaluation （GRADE） evidence evaluation， the comprehensive evaluation of effectiveness was Grade A. Pharmacoeconomic evaluation showed that JCs combined with calcium carbonate D3 tablets were more cost-effective than calcium carbonate D3 tablets alone in patients with OP. Compared with Gushukang capsules， JCs had more cost-effectiveness advantages， but the sample size included in the study was small， and the results needed to be verified by further studies. Combined with the results of the Comparative Assessment of Structure Prediction （CASP） evaluation list， the comprehensive economic evaluation was Grade B. JCs were the only bionic medicine of tiger bone in China with all intellectual property rights， with 3 national invention patents. Its process preparation and fingerprint detection had obvious technical advantages. It had innovative advantages in the supply base equipment， medicine resource management， production technology， and other aspects. Thus， its innovative comprehensive evaluation was Grade A. JCs were in capsule dosage form， which was relatively convenient for storage and transportation. The dosage form was suitable for indications， and the usage was easy for patients to grasp and accept. The statutory information and non-statutory information met the national standards. The comprehensive evaluation of suitability was Grade A. JCs did not contain toxic ingredients， had no restrictions on origin and prescription， and had abundant resources of original medicinal materials. The affordability of JCs in the treatment of OP was good in urban areas （14.97%） but not in rural areas （39.76%）. The price was higher than that of similar Chinese patent medicines， and the comprehensive evaluation of availability was Grade B. JCs had a reasonable proportion of natural animal bones， and their composition was basically the same as that of natural tiger bones. After marketing， more than 2 000 cases of real-world clinical research evidence was accumulated， and the comprehensive evaluation of TCM characteristics was Grade B. CSC v2.0 software was used for quantitative synthesis of the '6+1' dimension， and the comprehensive clinical value of JCs in the treatment of OP was Grade A. ConclusionJCs have good clinical value in the treatment of OP， and the TCM characteristics are prominent. It is suggested that JCs can be directly transformed into the related policy results of basic clinical drug management according to procedures.

Clinical outcome of single posterior implant-supported monolithic zirconia crowns fabricated using full digital workflow and conventional workflow: a 3-year follow-up / 中华口腔医学杂志

Objective: To compare the clinical performance of posterior single implant-supported monolithic zirconia crowns fabricated by full digital workflow and that of those fabricated by conventional workflow. Methods: This is prospective clinical research. Thirty-five patients who participated in a previous study during August 2017 to October 2018 at Department of Prosthodontics, Peking University School and Hospital of Stomatology were included in this 3-year follow-up study. The 35 patients, 17 females and 18 males, aged (49.0±15.4) years (24-86 years old), was allocated into two groups. In the full digital workflow group, intraoral scanning was taken immediately after implant placement, and a full zirconia implant crown was fabricated using model-free computer aided design/computer aided manufacturing (CAD/CAM) procedure (n=14). In the conventional group, a conventional impression was taken 3 months after implant placement and the stone model was produced. A full zirconia implant crown was fabricated using conventional model-based procedure (n=21). Three years following crown delivery, all the prostheses were evaluated in the aspect of color, surface roughness, contour and marginal integrity using modified US Public Health Service criteria (MUSPHS criteria). The soft and hard tissue around implant was evaluated using modified plaque index, probing depth (PD), number of implants with bleeding on probing, marginal bone loss (MBL). The biological and mechanical complication were also recorded. Statistical analysis was performed using independent samples t test, Mann-Whitney U test and Fisher's exact test. Results: The total survival rate of prosthesis and implant was 100% (35/35). No significant difference in MUSPHS criteria ratings on color, surface roughness, contour and marginal integrity of these crowns were found between the full digital workflow group and the conventional group (P>0.05). Sixteen out of the 35 crowns had a contour score of B due to loss of interproximal contact. Ten out of the 35 crowns had the screw hole sealing resin sinking or falling off, four in the full digital workflow group and six in the conventional group. There was no significant difference in the rate of prostheses mechanical complications between the two groups (P=1.000). For all the implants, there was no significant difference in MBL, PD, the modified plaque index, and number of implants with bleeding on probing between the two groups (U=119.50,133.00,142.50, t=-0.53, P>0.05). Conclusions: The clinical performance of implant-supported posterior single monolithic zirconia crowns fabricated by full digital workflow was stable. There was no significant difference in the clinical performance of the single implant crowns between the full digital workflow group and the conventional group.

Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain / 神经科学通报·英文版

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.

Protective effect of long non-coding RNA cytoskeleton regulatory RNA targeting microRNA-1246 on cell damage in Parkinson' s disease models / 解剖学报

Objective To story the effect of long non-coding RNA (IncRNA) cytoskeleton regulatory RNA (CYTOR) targeting microRNA (miR)-1246 on cell damage in Parkinson' s disease (PD) models. Methods SK-N-SH cells were exposed to 100 |xmol/L 1 -methyl-4-phenylpyridinium (MPP

Clinical comprehensive evaluation of Guanxin Shutong Capsules in treatment of coronary heart disease angina pectoris with heart blood stasis syndrome / 中国中药杂志

This study aims to comprehensively summarize articles on the treatment of coronary heart disease angina pectoris with heart blood stasis syndrome(CHD-AP-HBSS) by Guanxin Shutong Capsules(GSC), and comprehensively evaluate the evidence and value of the formula in "6+1" dimensions based on multi-criteria decision analysis(MCDA) model and Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021) with quantitative and qualitative methods, which is expected to highlight the clinical characteristics and advantages of the prescription and serve as a reference for medical and health departments. The dimensions are grade A, B, C, or D. In terms of safety, according to the reports from the spontaneous reporting system of National Center for ADR Monitoring, and literature analysis, GSC mainly results in the adverse reactions of mild or moderate nausea, diarrhea, rash, palpitation, and headache, with favorable prognosis in patients. Nevertheless, severe adverse reactions have been reported after marketing. Thus, additional evidence for its safety should be accumulated, and the current safety is grade B. Meta-analysis proves that GSC in combination with conventional treatment is superior to conventional treatment alone in alleviating AP and symptoms indicated by electrocardiogram(ECG). Therefore, the effectiveness of the medicine is grade A. As for the pharmacoeconomic value, based on the assumption that the per capita disposable income in 2020 is the willingness-to-pay threshold, it is more economical for CHD-AP patients to use GSC combined with conventional treatment than conventional treatment alone. However, as the currently available clinical parameters fail to support the difference in indirect cost between the two groups, the accuracy in the cost of intervention plan needs to be further improved. Therefore, the economy of the prescription is grade B. GSC has been awarded 13 national invention patents and 1 utility model patent, and won a lot of national and provincial patent awards, marking the enterprise service awareness and innovativeness. As a result, it is grade A in aspect of innovation. A questionnaire on the suitability of GSC suggests that publicity and promotion influence patients' choice and thus additional efforts should be made in this aspect. The suitability of this formula is grade B. Both rural and urban residents can afford the medicine for the whole course and the price is close to that of similar Chinese patent medicines. In addition, it is accessible regardless of season and place, so accessibility is grade A. As a Mongolian empirical formula destined to treat heart stabbing pain, it has the effects of activating blood and resolving stasis, dredging channels and activating collaterals, and moving Qi to relieve pain, and boasts the empirical evidence of more than 2 000 human cases. With prominent characteristics of traditional Chinese medicine, it is grade B. Based on the MCDA model and CSC v2.0, GSC is comprehensively class A in the treatment of CHD-AP-HBSS. The result can serve as a reference for basic clinical medication management.

Mathematical Model for Analyzing Five Flavor Compatibility-transformation Theory in Tangye Jingfatu / 中国实验方剂学杂志

Objective:<italic>Auxiliary Verse on Drugs and</italic> <italic>methods</italic> <italic>for Zang-Fu Organs （Fuxingjue Wuzangyongyao Fayao）</italic> written by TAO Hong-jing from the Liang dynasty covered many contents from<italic> </italic>a missing prescription book<italic> Classic of Decoction （Tangye Jingfa）</italic>， including a map revealing the compatibility principle of Chinese herbs， namely the Tangye Jingfatu. Represented by a centrosymmetric pentagon， the map describes a unique theoretical system for deficiency-excess syndrome differentiation of five Zang organs （liver， heart， spleen， lung and kidney） and the tonification-purgation and compatibility theory of five flavors （pungent， salt， sweet， sour and bitter）. Each Zang organ fixedly corresponds to one "property" flavor （purgation）， one "function" flavor （tonification） and one "transformation" flavor （harmonization） resulting from the combination of the former two. For example， the liver can be purged by sour， tonified by pungent， and moderated by sweet transformed by the combination of sour with pungent. The heart can be purged by bitter， tonified by salt， and astringed by sour transformed by the combination of bitter with salt. The spleen can be purged by pungent， tonified by sweet， and dried by bitter transformed by the interaction between pungent and sweet. The lung can be purged by salt， tonified by sour， and dispersed by pungent transformed by the combination of salt with sour. The kidney can be purged by sweet， tonified by bitter， and moistened by salt transformed by the combination of sweet with bitter. This study selected appropriate mathematical tools to analyze the fixed relationship between "property" flavor， "function" flavor and "transformation" flavor among the five Zang organs in “Tangye Jingfatu” and establish a mathematical model revealing the compatibility-transformation relationship among five flavors. Method:Based on the group representation of five elements （wood， fire， earth， metal， and water）， the correlations of "property" flavor， "function" flavor， and "transformation" flavor with five elements’ generation-restriction were deduced based on matrix calculation and group theory. The three-dimensional calculation method for vector product was expanded for establishing the mathematical operator of five flavors' compatibility-transformation. Result:<bold>and</bold> Conclusion:There is a mapping relationship of the purging， tonifying， and harmonizing functions represented by the "property" flavor， "function" flavor， and "transformation" flavor of the five zang organs in the "Tangye Jingfatu" with the five elements' generation-restriction. The established mathematical operator contributes to explaining the fixed collocations of five flavor transformation. Based on such algorithm， the tonifying and purging characteristics of five flavors in 10 representative classic prescriptions have been clearly expounded.

Potential Mechanism of Houttuyniae Herba Against Prostate Cancer： A Review / 中国实验方剂学杂志

According to the 2020 world cancer data report， the prevalence of prostate cancer ranks second in male malignant tumors and the mortality fifth. In China， due to the poor living and eating habits， the prevalence of prostate cancer is still rising， and advanced prostate cancer can adapt to and tolerate androgen castration related drugs through a variety of mechanisms， which often indicates poor therapeutic outcomes in the late stage. Houttuyniae Herba， a medicinal plant of family Saururaceae， has been officially identified both as food and medicine by the National Health Commission. The existing studies have shown that Houttuyniae Herba inhibits the proliferation， migration， and invasion of prostate cancer and induces its apoptosis and cell cycle arrest via multiple targets， links， and pathways. These anti-tumor activities can also be observed in breast cancer， leukemia， gastric cancer， colorectal cancer， and other tumor cells. Such activities are mainly related to the inhibited expression of cyclin and cyclin-dependent kinase， regulation of apoptosis-related proteins， activation of apoptosis-related pathways， reduced secretion of matrix metalloproteinase， inhibition of activator of transcription 3 （STAT3）/Zinc finger protein （Snail） / transcription factor twist signaling pathway， and antagonization of growth factor receptor， androgen， inflammation， and oxidative stress in promoting the occurrence and development of prostate cancer. In addition， Houttuyniae Herba is able to alleviate diabetes， regulate blood glucose-lowering pathways， and boost immunity by inhibiting the protein kinase B （Akt）/mammalian target of rapamycin （mTOR） and mitogen-activated protein kinase （MAPK） signaling pathways， thus suppressing the occurrence and progression of prostatic cancer. In conclusion，Houttuyniae Herba can be used as a potential drug against prostate cancer.

Research on the Development of O 2O Pharmaceutical Care Mode in China under the Internet Plus Background / 中国药房

OBJECTIVE：To provide reference for improving the level of pharmaceutical care in hospitals and promoting the continuous transformation and upgrading of O 2O pharmaceutical care mode in medical institutions in China. METHODS ：Using “Internet”“Network”“O2O”“Pharmaceutical care ”“Medication education ”“Chronic disease management ”“Medication consultation ” “Science popularization and education ”as keywords ，related literatures were collected from CNKI ，VIP，Wanfang and other Chinese databases during Jan. 2012-Mar. 2020. The development process ，characteristics，service content ，advantages and disadvantages of O 2O pharmaceutical care mode in China were analyzed and summarized ，and relevant suggestions were put forward. RESULTS & CONCLUSIONS ：O2O pharmaceutical care in Chinese hospitals covers prescription review and dispensing ， drug distribution ，medication consultation after visiting ，medication education ，chronic disease management ，science popularization and education ，pharmacy clinic ，etc.，realizing the whole process of closed-loop management. At present ，O2O pharmaceutical care in Chinese hospital had gradually moved from stage 1.0 to stage 2.0. Artificial intelligence technology has also been widely integrated into all aspects of pharmaceutical care ，assisting hospital pharmacists to better practice the “patient-centered”service concept，not only improving the quality and value of pharmacists ’pharmaceutical care more efficiently and accurately ，but also promoting the sinking of high-quality pharmaceutical resources and serving the grassroots. O2O pharmaceutical care shows the advantage of optimizing the allocation of pharmaceutical care resources ，expanding the scope of pharmaceutical care ，improving the relationship between doctors and patients ，diverting patients with different needs ，and promote hierarchical diagnosis and treatment. However，there are still some problems ，such as the failure to effectively cover rural patients ，the risk of patient privacy leakage ， and the lack of special quality management standards ，which hinder the further development and improvement of scale advantage of O2O pharmaceutical care. It is suggested to further improve the pharmaceutical care function of the platform ，expand the consumer population，promulgate relevant laws and regulations as soon as possible ，carry out continuing education and training for pharmacists according to the needs of patients in grassroots areas ，establish and improve relevant laws and regulations ，and improve O 2O pharmaceutical care quality management standards， so as to promote the development of O 2O pharmaceutical care mode in the hospital in China.

Clinical observation of arthroscopic single channel treatment of carpal tunnel syndrome with self-made instruments / 中国骨伤

OBJECTIVE@#To investigate the efficacy of self-made arthroscopic single channel in the treatment of carpal tunnel syndrome.@*METHODS@#Sixty patients with primary carpal tunnel syndrome treated from January 2014 to December 2019 were divided into arthroscopic group and traditional open operation group. There were 30 cases in arthroscopic group, including 12 males and 18 females, aged (47.5±4.5) years and the course of disease was (6.6±4.2) months. There were 30 cases in the traditional operation group, including 10 males and 20 females, aged (48.5±3.5) years, and the course of disease was (5.6±4.4) months. Both groups were unilateral. According to the anatomy of wrist joint and the characteristics of transverse carpal ligament and arthroscopy, the instruments including cannula, inner heart and hook knife were designed. The patients in two groups were treated with decompression of transverse carpal ligament using arthroscopy combined with self-made instruments and traditional open sergery. The incision length, operation time, intraoperative bleeding, hospitalization cost, hospitalization time and recovery time of the two groups were observed and compared. Boston Carpal Tunnel Questionnaire (BCTQ) score was used to evaluate the clinical efficacy of arthroscopy combined with self made instruments in the treatment of carpal tunnel syndrome.@*RESULTS@#Compared with the traditional group, the arthroscopic group had significant advantages in incision length, operation time, intraoperative bleeding and hospital stay, but the total cost of hospitalization was increased. The Boston score was significantly higher in the arthroscopic group than that in the traditional group at 1 month after operation, but not at 3 and 6 months after operation.@*CONCLUSION@#Arthroscopy combined with self-made instruments in the treatment of carpal tunnel syndrome is more reliable, minimally invasive and simplified than open surgery, but the patients should be clearly diagnosed and appropriately selected before operation to achieve satisfactory clinical effect.

Clinical comprehensive evaluation of Danhong Injection in treatment of stroke with blood stasis syndrome / 中国中药杂志

This study systematically reviewed the existing research on Danhong Injection in the treatment of stroke with blood stasis syndrome. The methods of evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, drug economics, mathematical statistics, and health technology assessment(HTA) were employed to qualitatively and quantitatively evaluate the "6+1" dimensions(safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine) of Danhong Injection through questionnaire survey, public information, real world data, and secondary evaluation of literature. With the weights given by experts, the multi-criteria decision analysis(MCDA) model was employed to measure each dimension and highlight the clinical value of Danhong Injection. Multi-source safety evidence showed that Danhong Injection had been fully monitored and studied. The severity of adverse reactions was mostly moderate or mild, and the prognosis was good. So it was rated as grade A for safety. Compared with Ligustrazine Injection, Fufang Danshen Injection and conventional treatment of western medicine, Danhong Injection had obvious advantages in clinical response rate and NIHSS score improvement in the treatment of stroke with blood stasis syndrome. So it was rated as grade A for effectiveness. Compared with Ligustrazine Injection and Yinxing Damo Injection, Danhong Injection had a cost-effectiveness advantage in the treatment of stroke with blood stasis syndrome, and the economic results were good. According to the existing evidence, the Danhong Injection was rated as grade B for economy. Danhong Injection had won a number of national patents, which was rated as grade A for its good innovation in guaranteeing supply measures, scalability of production capacity, and production process. It had good suitability for clinicians, nurses, pharmacists, and patients using the drug, and met the needs of clinical medication, so it was rated as grade B for suitability. Danhong Injection is rich in medicinal materials, stable in price, and sustainable. However, its availability needed to be further improved due to the limitation of prescription use, so it was rated as grade B for accessibility. Danhong Injection can promote blood circulation, resolve blood stasis, warm vessels, and smooth collaterals. It had accumulated more than 30 000 pieces of empirical evidence for human use in the real world. It had prominent characteristics of traditional Chinese medicine and was rated as grade B. CSC v2.0 was used for calculation, and the clinical value of Danhong Injection was comprehensively evaluated as class A, which could be directly translated into relevant policy results of basic clinical medication management according to the Guidelines for the Management Clinical Comprehensive Evaluation of Drugs(trial version 2021).

Pharmacoeconomic Evaluation of Perospirone in the Treatment of Schizophrenia ：A Study Based on Major Adverse Events / 中国药房

OBJECTIVE：To evaluate the economy of pe rospirone in the treatment of schizophrenia ，to provide guidance for clinically proper use of medications more cost-effectively ，and related health decision-making . METHODS ：A short-term decision tree model was constructed from the perspective of medical insurance payer to calculate the cost and health outcomes of different treatment plans considering major adverse events including extrapyramidal reaction ，weight gain ，diabetes，hyperlipidemia. The cost-utility of perospirone were compared with quetiapine ，aripiprazole and olanzapine respectively ，using QALYs as the measure of health outcomes ，3 times GDP per capita as the willingness-to-pay threshold ；probability sensitivity analysis was performed. RESULTS：The results of base-case analysis showed that the cost of perospirone （6 688.25 yuan）was lower than those of quetiapine （9 887.45 yuan），aripiprazole（13 284.65 yuan）and olanzapine （15 332.80 yuan）. The utility of perospirone （0.79 QALYs）was better than those of quetiapine （0.76 QALYs），aripiprazole（0.77 QALYs）and olanzapine （0.75 QALYs）. Compared with quetiapine ， aripiprazole and olanzapine ，peropirone had lower cost and higher health outcome ，which indicated that strong dominance favors perospirone over the other 3 drugs. The results of sensitivity analysis were consistent with those of base-case analysis. CONCLUSIONS：Perospirone has economic advantages in treating schizophrenia patients compared to other commonly used atypical antipsychotic drugs.

Construction of Post Competency Evaluation Index System for Drug Registration Specialist / 中国药房

OBJECTIVE：To esta blish a sc ientific and objective post competency evaluation index system for the drug registration specialist. METHODS ：By searching the competency model literature of drug registration and registration related documents，combined with Spencer ’s Competency Dictionary and Hay ’s Competency Dictionary ，post competency evaluation index system for drug registration specialist was formulated preliminarily. Through two rounds of Delphi expert consultation ，experts in related fields of drug registration were consulted by letter ，the evaluation indexes were screnned and revised ，and the weight of the indexes was calculated by using the superior order diagram method. Based on questionnaire survey ，232 drug registration personnel were selected as research objects ，and then exploratory factor analysis ，confirmatory factor analysis and internal consistency reliability analysis were used to test the constructed evaluation index system. RESULTS ：The post competency evaluation system of drug registration specialist covered 4 core dimensions （registered professional ability ，relationship management ability ，professional development ability ，personal comprehensive quality ），11 sub-scales，and 41 measurement items ；the weight of the index was confirmed. The establishment process of the evaluation system showed that the expert consultation had high enthusiasm and good coordination；exploratory factor analysis and confirmatory factor analysis had proved the scientific rationality of the index system. CONCLUSIONS：The post competency evaluation index system for drug registration specialist is comprehensive ，integrated and scientific，can provide reference for evaluation and management of the drug registration specialist practice.

The effect of bulk electron density on the dose accuracy of treatment planning for postoperative cervical cancer / 中华放射医学与防护杂志

Objective:To study the impact on dose accuracy for the treatment planning by manually assigning accurate electron density for CT image-based tumor tissues and organs at risk.Methods:Twenty cases of retrospective postoperative cervical cancer radiotherapy plans were selected. The body electron density of the corresponding organs was derived from the ICRU 46 report and assigned in the treatment planning system (Monaco5.11, Sweden), including the bladder, rectum, intestine, kidney, spinal cord, femoral head, and ilium. The original plans were double-arc volumetric modulated arc therapy plan (360° VMAT), using Monte Carlo algorithm, the calculation grid was 0.3 cm × 0.3 cm × 0.3 cm, and the minimum subfield width was 0.6 cm. Keep the original plan fluence unchanged and recalculate the dose to generate a new plan. The two-dimensional dose distribution and dose-volume histogram (DVH) were used to compare the differences between the two plans. The difference was compared between the two group plans by using the dosimetry parameters and DVH two dimension curve.Results:For the planning of assigning bulk electron density (Plan RED), the deviation of the patient′s target dose parameters and the original plan (Plan ref) was <2%, and the average deviation of all target regions D2, D98, Dmean was < 0.7%, only 2 of the 180 data were between 2% and 3%. The average deviation of V20, V30, D1 cm 3, Dmean of the bladder, rectum, and small intestine, the original Plan ref was less than 0.6%, and 4 out of 240 data had values > 2%. Plan RED′s average hop count was 0.9% higher than Plan ref, and the total number of subfields remains unchanged. The planned dose generated by manually assigning the electron density in Plan RED was higher than that in Plan ref, but met the clinical requirements. The two-dimensional curves of the DVH diagram for targets and OARs almost completely overlapped, and there was no obvious difference in the dose distribution diagram of the same cross section. The statistical result of all parameters showed that the difference in planned dose parameters between the two groups was not statistically significant( P>0.05). Conclusions:The overall deviation of dose accuracy between Plan RED and Plan ref is <2%, which meets the clinical requirements and provides a reference for realizing MRI-only treatment planning.

Responses of Primary Afferent Fibers to Acupuncture-Like Peripheral Stimulation at Different Frequencies: Characterization by Single-Unit Recording in Rats / 神经科学通报·英文版

The pain-relieving effect of acupuncture is known to involve primary afferent nerves (PANs) via their roles in signal transmission to the CNS. Using single-unit recording in rats, we characterized the generation and transmission of electrical signals in Aβ and Aδ fibers induced by acupuncture-like stimuli. Acupuncture-like signals were elicited in PANs using three techniques: manual acupuncture (MAc), emulated acupuncture (EAc), and electro-acupuncture (EA)-like peripheral electrical stimulation (PES). The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz, respectively. The frequency of discharges in PANs was correlated with the frequency of PES. The highest discharge frequency was 246 Hz in Aβ fibers and 180 Hz in Aδ fibers. Therefore, EA in a dense-disperse mode (at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc. Frequencies of EA output >250 Hz appear to be obsolete for pain relief.