Mental state is an important part of the normal life activities of the human body, and it is also the most external expression and the most easily obtained information of the physical condition. The normal activities of the mind depend on the normal operation of the viscera, qi, and blood, and are a unified whole that prospers together and suffers together. The theory of the five-spirit-viscera in the Yellow Emperor’s Inner Classic revealed that the normal mental activities of the human body were dominated by the five internal organs, that is, the five internal organs were the body and the five spirits were the function. And it highlighted the viewpoint that the five internal organs store the spirits and are actually one. The heart governs the spirit and belongs to the four internal organs. On this basis, Synopsis of Golden Chamber used the internal organs to diagnose and treat mental diseases, integrating the theory of the five spirits into it, forming a unique method of diagnosis and treatment with the heart as the leading factor and regulating the qi and blood of the four internal organs. It identified the pathogenesis of diseases such as pathogenic crying, lily disease, and hysteria from five levels: heart deficiency and weak qi, heart-lung disharmony, heart-liver disharmony, the heart of the loss of the spleen nourishment, and disharmony between heart and kidney. The treatment was mainly to replenish the deficiency of the viscera and eliminate the pathogens, reflecting the characteristics of regulating the mind and calming the four internal organs. This unique view on diagnosis and treatment has profoundly influenced the diagnosis and treatment theories of mental illnesses by later doctors, and is of great significance to the current clinical treatment of such illnesses.

Objective:To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA) who failed anti-retroviral therapy (ART) in Henan Province, in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods:PLWHA with virological failure (human immunodeficiency virus (HIV) RNA≥500 copies/mL) after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022. Baseline CD4 + T lymphocyte counts, ART regimens and other clinical data were collected. HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People′s Hospital of Zhengzhou, and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results. Genotypic drug resistance to nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase inhibitors (INSTI) was determined. Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure. Results:Among 982 PLWHA, the sequences of 899 cases were successfully amplified, and drug resistance was detected in 737 cases, with the drug resistance rate of 81.98%(737/899). The rates of resistance to NRTIs, NNRTIs, PIs and INSTIs were 71.97%(647/899), 79.31%(713/899), 5.23%(47/899) and 2.72%(20/734), respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases (79.78%), mainly NRTI and NNRTI concomitant resistance in 583 cases (79.10%). There were 99 cases (13.43%) who developed resistance to only one class of drugs, and those who developed concurrent resistance to three classes of drugs were 48 cases (6.51%), and two cases (0.27%) were found to be resistant to all four classes of drugs mentioned above. A total of 10 HIV genotypes were detected, among which subtype B accounted for the most (59.73%(537/899)), followed by circulating recombinant form (CRF)01_AE subtype (21.91%(197/899)) and CRF07_BC subtype (9.45%(85/899)). The risk factors affecting the development of drug resistance were baseline CD4 + T lymphocyte counts, ART regimens and HIV-1 genotypes. The risk of drug resistance in patients with baseline CD4 + T lymphocyte counts <100/μL was 4.55 times (95% confidence interval ( CI) 2.69 to 7.70) higher than patients with CD4 + T lymphocyte counts≥250/μL, the risk of drug resistance in patients using 2NRTIs+ NNRTI regimen was 4.51 times (95% CI 1.75 to 11.63) higer than those using 2NRTIs+ INSTI regimen, and patients infected with B and CRF01_AE subtype was 2.18 times (95% CI 1.10 to 4.29) and 2.70 times (95% CI 1.26 to 5.78) higer than those with CRF07_BC subtype, respectively. Conclusions:The incidence of genotypic drug resistance in PLWHA with ART failure in Henan Province is high. Low baseline CD4 + T lymphocyte counts, 2NRTIs+ NNRTI regimens, and genotype B and CRF01_AE are risk factors for drug resistance in PLWHA.

Background::Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP.Methods::We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia. Results::mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485. Conclusion::High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.

Humans ; Mutation/genetics* ; HIV Infections/drug therapy* ; Drug Resistance ; Treatment Failure ; China ; Drug Resistance, Viral/genetics*

Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg^-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg^-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.

Objective:To analyze the drug resistance characteristics of HIV/AIDS patients in Henan Province with antiretroviral treatment (ART) failure through the genotypic drug resistance detection.Methods:Blood samples were collected from HIV/AIDS patients who received ART for more than 6 months with viral loads ≥1 000 copies/ml in 18 cities of Henan from January 2018 to May 2021. The genotypic drug resistance detection was conducted by using an In-house drug resistance detection method. The drug resistance mutation (DRM) and antiretroviral susceptibility were analyzed by submitting the determined sequences to the Stanford HIV-1 drug resistance database. The information about patients' demographic characteristics and antiviral treatment data were collected.Results:A total of 887 HIV/AIDS patients with ART failure, 812 sequences were successfully amplified with the success rate of 91.54%. In the 812 patients, 676 were drug resistant (83.25%, 676/812). The drug resistance ratesto nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 73.40% (596/812), 80.54% (654/812), 5.54% (45/812), and 2.56% (17/663), respectively. There were significant differences in drug resistance rates among four types of drugs ( χ2=1 686.34, P<0.001). The drug resistance rate to two drugs was 66.38% (539/812), and the drug resistance rate to three drugs was 5.79% (47/812). A total of 9 subtypes of HIV-1were detected, in which subtype B accounted for 59.61%(484/812), followed by subtype CRF01_AE (22.17%, 180/812) and subtype CRF07_BC (9.48%, 77/812). There were significant differences in drug resistance rate among different subtypes ( χ2=21.33, P=0.001). Among NRTIs related mutation sites, the DRM rate of M184V/I was highest (63.42%, 515/812), followed by K65R (27.46%, 223/812). The top three DRM rates were detected for K103N/S (34.98%, 284/812), G190A/S (26.11%, 212/812) and V106M/I (24.63%, 200/812) among NNRTIs related mutation sites, and M46I (4.31%, 35/812), V82A/F (3.82%, 31/812), and I54V/MV (3.69%, 30/812) among PIs related mutation sites. While among INSTIs related mutation sites, E157Q/EQ had the highest DRM rate (3.47%, 23/663), followed by R263K (0.75%, 5/663) and G140A (0.75%, 5/663). The resistance to lamivudine and emtricitabine of NRTIs was at high-level (65.52%, 532/812), and the resistance to nevirapine (77.46%, 629/812) and efavirenz (71.18%, 578/812) of NNRTIs was also at high-level. The medium/high-level resistance to lopinavir/ritonavir of PIs was only 4.19% (34/812), the medium/high-level resistance to elvitegravir and raltegravir of INSTIs was 1.66% (11/663) and 1.21% (8/663), respectively, and no high-level resistance to bictegravir or dolutegravir was found. Conclusions:The drug resistance in HIV/AIDS patients with ART failure was high in Henan, characterized by high drug resistance rates to NRTIs and NNRTIs, and diverse and complex resistance mutations. So high resistance barrier ART-regimens were recommended, and the viral load monitoring and drug resistance testing after ART should be strengthened.

Objective: To construct a mouse derived pcDNA3. 1 ⁃3 × Flag⁃c⁃NUP85 expression plasmid and observe its effect on expression of inflammation factors in LPS⁃induced RAW264. 7 cells , as well as on the proliferation and apoptosis of RAW264. 7 cells. Methods: The NUP85 gene was amplified by PCR to construct pcDNA3. 1 ⁃3 × Flag-c⁃NUP85 eukaryotic expression plasmid. The pcDNA3. 1 ⁃3 × Flag⁃c vector was divided with enzymes. The purified PCR product was ligated with the vector, and the ligated product was transformed into bacterial competent cells. After identification by enzyme digestion , sequencing and analysis were performed. Then , it was transfected into RAW264. 7 cells , and the blank plasmid without NUP85 gene was set as the control group. The effect on cell proliferation and apoptosis were detected by CCK⁃8 assay and flow cytometry , and the expression of inflammatory cytokines such as tumor necrosis factor⁃α (TNF⁃α ) and interleukin⁃6 (IL⁃6) in LPS⁃induced RAW264. 7 cells was detected by Western blot and ELISA. Results: Enzyme digestion identification and Western blot results showed that pcDNA3. 1 ⁃3 × Flag⁃c⁃NUP85 eukaryotic expression plasmid was successfully constructed and expressed. The results of CCK⁃8 assay showed that the cell survival rate of NUP85 overexpression group was significantly lower than that of control group after 24 h[(0. 55 ± 0. 03) vs (0. 67 ± 0. 05) , F = 30. 98 , P < 0. 05 ] . The results of flow cytometry showed that the cell apoptosis rate of NUP85 overexpression group was higher than that of control group[( 15. 78 ±1. 05)% vs ( 13. 40 ± 0. 47)% , F = 75. 38 , P < 0. 05] . The results of Western blot and ELISA showed that after transfection of pcDNA3. 1 ⁃3 × Flag⁃c⁃NUP85 , the expression of TNF⁃α and IL⁃6 in RAW264. 7 cells were higher than those in the control group ,with statistical significance (P < 0. 05) . Conclusion NUP85 can inhibit the proliferation and promote apoptosis in LPS⁃stimulated RAW264. 7 cells , and NUP85 can promote the expression of inflammatory cytokines IL⁃6 and TNF⁃α in LPS⁃stimulated RAW264. 7 cells.

Objective : To analyze the application value of metagenomic next-generation sequencing (mNGS) in the detection of pathogenic bacteria in pulmonary infection ，and to provide a theoretical basis for clinical diagnosis. Methods : A retrospective study was conducted on 161 patients with suspected pulmonary infection，and samples of bronchoalveolar lavage fluid ，sputum and lung tissue were collected specimens ，pleural effusion and blood were simultaneously subjected to routine culture，respiratory pathogen nucleic acid detection and pathogenic microorgan- ism mNGS detection．The sensitivity ，specificity，positive predictive value ，and negative predictive value of the three detection methods were calculated respectively to evaluate the clinical application value of mNGS. Results: Among 161 patients with suspected pulmonary infection，113 cases were finally confirmed as pulmonary infection. Among the 161 patients enrolled，the sensitivity and negative predictive value of mNGS were improved compared with routine culture and nucleic acid detection of respiratory pathogens，and the difference was statistically signifi- cant(P＜0. 001) ．Although the specificity of mNGS was higher than that of respiratory pathogen nucleic acid de- tection，the difference was not statistically significant．The positive predictive value of mNGS was the highest，and was higher than that of respiratory pathogen nucleic acid detection，but had no statistical significance compared with conventional culture． Conclusion The sensitivity of mNGS in the diagnosis of pathogenic microorganisms in pul- monary infection is higher than that of conventional culture and nucleic acid detection of respiratory pathogens， which reduces the false negative rate of diagnosis and has a better comprehensive evaluation ; conventional culture detection has low sensitivity，but high specificity ; respiratory pathogen nucleic acid detection compared with con- ventional culture，the sensitivity is improved，but the specificity decreased.

OBJECTIVE To systema tically evaluate the effectiveness and safety of gen eric and original drugs of atorvastatin ， and to provide the latest evidence-based reference for drug selection in clinic. METHODS Retrieved from PubMed ，Cochrane Library，Embase，CNKI，VIP and Wanfang database ，intervention trials and observational studies about generic and original drugs of atorvastatin were collected during the inception to Apr. 2021. After data extraction of literatures met inclusion criteria ，the Cochrane risk bias evaluation tool 5.1.0 was used to evaluate the quality of intervention trials ；Newcastle-Ottawa Scale （NOS）was used to evaluate the quality of observational studies. RevMan 5.4 software was used to conduct meta-analysis ，and descrptive analysis was performed at the same time. RESULTS A total of 24 studies were included ，involving 21 randomized controlled trials （RCTs）and 3 retrospective cohort studies （RCSs），with 20 001 patients involved. Meta-analysis results of RCT showed there was no statistically significant difference between the two groups in reducing low-density lipoprotein cholesterol （LDL-C）levels [MD ＝ － 0.05，95％ CI（－ 0.12，0.02），P＝0.16] and increasing Δ 基金项目：国家重点研发计划项目（No.2017YFC0910004）；山 东省重点研发计划项目（No.2020RKB14165） high-density lipoprotein cholesterol （HDL-C）levels [MD ＝ ＊硕士研究生 。研究方向：临床药学。E-mail：1677032023@qq. － 0.00，95％ CI（－ 0.02，0.01），P＝0.52]；the degree of com reducing total cholesterol （TC）level [MD ＝－0.11，95％CI # 通信作者：主任药师，硕士生导师。研究方向：临床药学、药事 （ － 0.17，－ 0.06），P＜0.000 1] and triglyceride （TG） 管理。电话：0351-89268349。E-mail：13791120711@126.com level [MD ＝－0.05，95％CI（－0.09， －0.01），P＝0.02] in ·358· China Pharmacy 2022Vol. 33 No. 3 中国药房 2022年第33卷第3期 generic drug group was lower than orig inal drug group ，with statistical significance difference. There was no statistical significance difference in total incidence of adverse drug reaction （ADR）[OR＝1.08，95％ CI（0.85，1.37），P＝0.55] and the incidence of other ADR（P＞0.05）. The results of subgroup analysis showed that the reductions of TC and TG of generic drugs produced by Beijing Jialin Pharmaceutical Enterprise （hereinafter refer to Jialin generic drugs ）were less than those of the original drug ，and the difference was statistically significant ；compared with original drugs ，there was no significant difference in other indexes or all indexes of the generic drugs from other manufacturers. Compared with original drugs ，the reductions of TC and TG in 20 mg/d group of Jialin generic drugs were less than original drug group ；the degree of TC reduction at 12 and 24 weeks of follow-up and TG reduction at 24 weeks of follow-up were less than those of the original drugs ，the difference was statistically significant ；there was no significant difference in other indexes. The qualitative description of RCS showed that for elderly patients with death/acute coronary syndrome ，there was no statistical difference between the two groups in terms of cardiovascular events or serious side effects. For the adult patients who switched from original drugs to generic drugs ，the effect of generic drugs instead of original drugs would not be reduced ，but the increase of HDL-C was less than that of original drug. CONCLUSIONS In terms of effectiveness，generic drugs of atorvastatin can replace original drugs and caution should be taken on the levels of HDL-C ，TC and TG for long time use ；in terms of safety ，generic drugs are similar to the original drugs.

The identification of oleaginous yeast species capable of simultaneously utilizing xylose and glucose as substrates to generate value-added biological products is an area of key economic interest. We have previously demonstrated that the Cutaneotrichosporon dermatisNICC30027 yeast strain is capable of simultaneously assimilating both xylose and glucose, resulting in considerable lipid accumulation. However, as no high-quality genome sequencing data or associated annotations for this strain are available at present, it remains challenging to study the metabolic mechanisms underlying this phenotype. Herein, we report a 39,305,439 bp draft genome assembly for C. dermatis NICC30027 comprised of 37 scaffolds, with 60.15% GC content. Within this genome, we identified 524 tRNAs, 142 sRNAs, 53 miRNAs, 28 snRNAs, and eight rRNA clusters. Moreover, repeat sequences totaling 1,032,129 bp in length were identified (2.63% of the genome), as were 14,238 unigenes that were 1,789.35 bp in length on average (64.82% of the genome). The NCBI non-redundant protein sequences (NR) database was employed to successfully annotate 11,795 of these unigenes, while 3,621 and 11,902 were annotated with the Swiss-Prot and TrEMBL databases, respectively. Unigenes were additionally subjected to pathway enrichment analyses using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Cluster of Orthologous Groups of proteins (COG), Clusters of orthologous groups for eukaryotic complete genomes (KOG), and Non-supervised Orthologous Groups (eggNOG) databases.Together, these results provide a foundation for future studies aimed at clarifying the mechanistic basis for the ability of C. dermatis NICC30027 to simultaneously utilize glucose and xylose to synthesize lipids.