OBJECTIVE: This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. METHODS: A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. RESULTS: A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. CONCLUSION The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
Humans ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV-1/genetics* ; Cross-Sectional Studies ; Phylogeny ; Anti-HIV Agents/therapeutic use* ; Drug Resistance, Viral/genetics* ; HIV Infections/epidemiology* ; Mutation ; China/epidemiology* ; Prevalence ; Genotype

The establishment of core indicators for assessment plays an important role in carrying out the lifecycle value assessment of Chinese patent medicine, which are developed based on the concepts such as clinical value oriented, paying attention to the human use experience, and whole process quality control. To this end, the Specialty Committee of Data Monitoring and Decision Making of the World Federation of Chinese Medicine Societies organized experts to draft the Expert Consensus on Core Indicators for Lifecycle Value Assessment of Chinese Patent Medicine based on the research including Chinese Medicine Registration Review Evidence System in Combination of Traditional Chinese Medicine Theory, Human Use Experience, and Clinical Trials(GZY-FJS-2022-206) by National Administration of Traditional Chinese Medicine. This consensus proposed 92 core indicators from four stages, including new drug R&D project approval, pre-clinical research, new drug marketing authorization, and post-marketing, combining the assessment purposes and needs of different stakeholders from different dimensions such as clinical needs, clinical positioning, human use experience, effectiveness, safety, quality control, innovation, accessibility, and suitability. This consensus also interpreted the indicators to clearly elucidate the core elements of the value assessment of Chinese patent medicine in different R&D stages and guided the stakeholders to identify, analyze, and assess the value of Chinese patent medicine in the R&D and use process based on the core indicators in a scientific, objective, and standardized approach. This consensus is expected to play an important role in the high-quality new drug development, drug pricing and compensation of Chinese patent medicine, the development of clinical pathways, and rational clinical application.
Humans ; Nonprescription Drugs/therapeutic use* ; Consensus ; Medicine, Chinese Traditional ; Quality Control ; Drug Approval ; Drugs, Chinese Herbal/therapeutic use*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

[Abstract] Objective To investigate the effect and possible mechanism of cell cycle-dependent kinase (Cdk)5 inhibitor Roscovitine on 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced pathological changes in brain regions associated with Parkinson’ s disease (PD) model mice. Methods The effect of Roscovitine on the relative expression levels of P25 and Cdk5 proteins was detected by Western blotting in MPP

Objective: To investigate the clinical characteristics of hereditary hypercholesterolemia in childhood. Methods: The clinical data including general conditions, clinical manifestations, laboratory tests, and genetic testing results of 4 children with hereditary hypercholesterolemia who admitted to Henan Children's Hospital from January 2020 to December 2020 were retrospectively analyzed. Results: There were 4 female children aged 5.5,1.5,6.3,3.1 years, all presented with skin xanthoxoma as the chief complaint. Plasma total cholesterol (range 11.8 to 20.9 mmol/L) and low density lipoprotein-cholesterol (range 8.2 to 13.7 mmol/L) were significantly elevated. The serum β-glutamate levels in case 1 (241.2 μmol/L) and case 2 (164.2 μmol/L) increased significantly. Genetic analysis revealed compound heterozygous variants of ABCG8 gene in case 1 and ABCG5 gene in case 2 who were diagnosed with sitosterolemia. Case 3 and 4 who all had family history of hypercholesterolemia and compound heterozygous variants of LDLR gene were diagnosed with familial hypercholesterolemia. After diet treatment, the blood lipids returned normal and the skin xanoma subsided in case 1 and 2. In case 3 and 4, the blood lipids gradually decreased after diet and rosuvastatin treatment. Conclusions: Xanthomatosis is the common clinical manifestation of sitosterolemia and familial hypercholesterolemia. Family history, blood plant sterol profile, genetic variation, and changes in blood lipids after early dietary treatment are helpful for disease identification.
Child ; Humans ; Hypercholesterolemia/genetics* ; Retrospective Studies ; Hyperlipoproteinemia Type II/genetics* ; Cholesterol, LDL

Objective: miR-663a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of miR-663a during radiation-induced Epithelium-to-mesenchymal transition (EMT). Methods: TGF-β1 or IR was used to induce EMT. After miR-663a transfection, cell migration and cell morphological changes were detected and the expression levels of miR-663a, TGF-β1, and EMT-related factors were quantified. Results: Enhancement of cell migration and promotion of mesenchymal changes induced by either TGF-β1 or radiation were suppressed by miR-663a. Furthermore, both X-ray and carbon ion irradiation resulted in the upregulation of TGF-β1 and downregulation of miR-663a, while the silencing of TGF-β1 by miR-663a reversed the EMT process after radiation. Conclusion Our findings demonstrate an EMT-suppressing effect by miR-663a via TGF-β1 in radiation-induced EMT.
Down-Regulation ; Epithelial-Mesenchymal Transition ; Epithelium/metabolism* ; MicroRNAs/metabolism* ; Transforming Growth Factor beta1/pharmacology*

Objective: To investigate the expression of long non-coding RNA LOC101927476 (LncRNA LOC101927476) in ovarian cancer and its effect on the biological characteristics of ovarian cancer. Methods: Patients with ovarian cancer who underwent surgery in Cancer Hospital of Chinese Academy of Medical Sciences from 2018 to 2019 were selected. The expressions of LOC101927476 in ovarian cancer cells 3AO, OVCA429, TOV21G, A2780, SKOV3, as well as 22 primary tumor tissues and their matched metastatic tumor tissues were detected by real-time quantitative polymerase chain reaction (RT-PCR). Ovarian cancer transcriptome sequencing data from the TCGA database was used to verify the expressions of LOC101927476 and GATA4. 3AO and OVCA429 cells were infected with lentivirus plasmid containing OE-LOC101927476 and single guide RNA (sg-RNA) targeting LOC101927476, respectively. The effects of LOC101927476 on migration and invasion were detected by Transwell and wound healing assay. The effect of LOC101927476 on cell proliferation was detected by cell counting kit-8 (CCK-8) assay. Results: RT-PCR assay showed that 20 out of 22 patients had significantly lower expression of LOC101927476 in their metastatic tumors compared with primary tumors. Transwell assay showed that overexpression of LOC101927476 significantly inhibited the invasion and migration capacities of 3AO cells. The numbers of invading and migrating 3AO cells infected with OE-LOC101927476 lentivirus were (357±63) and (699±65), respectively, lower than (661±95) and (1 024±76) in OE-EV group (P<0.050). In contrast, the numbers of invading and migrating OVCA429 cells with LOC101927476 knockdown were (512±72) and (472±40), respectively, higher than (309±13) and (363±27) in sg-Control group (P<0.050). Wound healing assay results showed that after 48 hours, the percentage of scratch healing of 3AO cells in OE-LOC101927476 group was (10.86±0.63)%, significantly lower than (57.38±4.42)% of OE-EV group (P=0.009). After 24 hours, the percentage of scratch healing of OCVA429 cells in sg-LOC101927476 group was (59.98±1.34)%, significantly higher than (23.15±2.03)% of sg-Control group (P=0.004). CCK-8 assays showed that the OD value of 3AO cells in OE-LOC101927476 group was (2.07±0.08), significantly lower than (2.29±0.04) of OE-EV group (P=0.009). The OD value of OVCA429 cells in sg-LOC101927476 group was (2.13±0.03), significantly higher than (1.93±0.03) of sg-Control group (P=0.001). The relative expression of GATA4 in OE-LOC101927476 group was (1.86±0.25), significantly higher than 1.00 of OE-EV group (P=0.001). In patients with high expression of LncRNA LOC101927476, the expression level of GATA4 was (2.93±0.35), which was higher than (0.29±0.06) of LOC101927476 low expression group (P=0.001). Conclusion: LncRNA LOC101927476 can inhibit the invasion, migration and proliferation of ovarian cancer cells.
Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Female ; Humans ; Neoplasm Invasiveness ; Ovarian Neoplasms/genetics* ; RNA, Long Noncoding/genetics*

Asians ; China ; Humans ; Hypertension/drug therapy* ; Practice Guidelines as Topic ; Writing

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.
Humans ; Practice Guidelines as Topic

[Abstract] Objective To investigate the effects of the downregulation of draxin expression on the projection characteristics of 23C10-positive neural fibers in the chick embryonic hindbrain. Methods The vitro incubation of HH stages 21-22 chick embryonic hindbrain biopsy with alkaline phosphatase (ALP) protein was used as control group. The incubation of HH stages 21-22 chick embryonic hindbrain biopsy with draxin-ALP fusion protein was used as experimental group. The number of embryonic hindbrain for each group was 10. To detect whether 23C10-positive neural fibers could directly bind to draxin protein or not;In ovo electroporation using empty vector in the chick embryonic hindbrain was used as control group. In ovo electroporation with small interfering RNA(siRNA) expressing vector for reducing draxin expression in the chick embryonic hindbrain was used as experimental group. The number of embryonic hindbrain for each group was 18. The effect of the down-regulation of draxin expression and the change of projection characteristics of 23C10-positive neural fibers were observed to check whether the down-regulation of draxin expression would affect the distribution of 23C10-positive fibers. Results Most portion of draxin protein could overlap with 23C10-positive neural fibers in HH stages 21-22 chick embryonic hindbrain biopsies; After expression of the siRNA plasmid against draxin by electroporation, the expression level of draxin protein was significantly reduced, and the distribution of 23C10-positive fibers was scattered in the dorsal hindbrain on the electroporated side at HH stages 25-26 of chick embryos (P < 0. 05) . Conclusion Draxin protein may directly bind to 23C10-positive fibers in hindbrain, and it plays an important regulatory role in the fasciculation of 23C10-positive fibers during chick embryonic development.