Aim To investigate the regulatory effects of 3-bromopyruvate (3-BrPA) on apoptosis and autophagy of fibroblast-like synoviocytes (FLS) in rats based on AMPK/mTOR signaling pathway and the underlying mechanism. Methods FLS of rats in vitro were cultured and induced by tumor necrosis factor-α (TNF-α) to construct a model of rheumatoid arthritis (R A). MTT assay was used to explore the optimal concentration of TNF-α and 3 -BrPA for induction and treatment of FLS. The effects of 3-BrPA on the migration and invasion of FLS were detected by Wound healing assay and Transwell assay. The apoptosis of FLS was tested by flow cytometry and mitochondrial membrane potential assay kit (JC-1). Moreover, FLS autophagic flux was detected by mCherry-EGFP-LC3B-overexpressed plasmids, and the expression of apoptosis/autophagy-related proteins as well as AMPK/mTOR pathway-related proteins were detected by Western blot. Results 3-BrPA (15 μmol • L) significantly inhibited the proliferation, migration, and invasion of FLS stimulated by TNF-a (25 μg • L

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

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

OBJECTIVE: To investigate the application effect of sequential autologous hematopoietic stem cell transplantation (Auto-HSCT) with lenalidomide, bortezomib and dexamethasone (RVD) in the treatment of multiple myeloma (MM) evaluated by propensity score matching. METHODS: The clinical data of 49 MM patients treated with RVD scheme and followed-up for 36 months in the hospital from January 2015 to January 2021 were retrospectively analyzed and included in the control group, the clinical data of 54 MM patients who received RVD scheme and sequential Auto-HSCT scheme and completed 36 months of follow-up in the hospital during the same period were collected and included in the observation group. PSM method (1∶1, caliper value=0.01) was used to match the control group with the observation group based on baseline data and laboratory indexes, covariate equilibrium samples were obtained between groups (40 cases in each group). The clinical efficacy of patients in the two groups after 18 weeks of treatment was compared; the incidence of toxic and side effects during treatment of patients in the two groups was compared; the survival of patients in the two groups was compared after 36 months of follow-up. RESULTS: The ORR and DCR in the observation group were higher than those in the control group, the difference was statistically significant (P<0.05). Compared the incidence of fatigue, rash, thrombocytopenia, anemia and nausea of patients in the two groups, there was no statistical significant difference (P>0.05). After 36 months of follow-up (no loss during follow-up), 4 cases died from illness in the observation group, with a survival rate of 90% and an average survival time of 35.61 (95% CI: 35541-35.685) months, 10 cases died from illness in the control group, with a survival rate of 75% and an average survival time of 34.70 (95% CI: 34.559-34.832) months, the survival rate of the observation group was higher than that of the control group, the difference was statistically significant (P<0.05). CONCLUSION Sequential Auto-HSCT with RVD regimen in the treatment of MM can improve the short-term efficacy and increase the survival rate of patients, which will not increase toxic and side effects and has high safety.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bortezomib/therapeutic use* ; Dexamethasone ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Multiple Myeloma/drug therapy* ; Propensity Score ; Retrospective Studies ; Transplantation, Autologous/methods* ; Treatment Outcome

Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.

Objective:To compare the characteristics of four commonly adopted animal models of hyperuricemia （HUA） for traditional Chinese medicine （TCM） screening， so as to choose the adequate model for screening Chinese herbs and herbal compounds capable of lowering the uric acid. Method:Fifty-four male SD rats were randomly divided into nine groups， namely the normal group， hypoxanthine （HX） + oxonic acid potassium salt （OAPS） model group， yeast extract （YE） + OAPS model group， low-dose adenine （AD） + ethambutol （EMB） model group， high-dose AD + EMB model group， and four positive drug allopurinol （Allo） groups. The modeling lasted for 14 d. The levels of serum uric acid （SUA）， urinary uric acid （UUA）， serum creatinine （SCr）， urea nitrogen （BUN）， kidney injury molecule 1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL） were detected on the 3rd， 7th， and 14th days. Urine was collected on the 7th and 14th days to investigate changes in urine volume， and the crystals in the residual urine were observed under a polarizing microscope. After the modeling， the kidney was harvested and weighed， followed by pathological examination. Result:The urine volumes in the HX + OAPS model group and high-dose AD + EMB model group were significantly reduced （P<0.05）. The renal indexes of each model group， except for the YE + OAPS model group， were significantly elevated （P<0.05， P<0.01）. The increase in SUA of the HX + OAPS model group and YE + OAPS model group started later （P<0.05）. The KIM-1 and NGAL levels of the HX + OAPS model group rose significantly from the 7th day （P<0.05， P<0.01）， and the BUN increased significantly on the 14th day （P<0.05）. There was no significant difference in the above-mentioned indicators in the YE + OAPS model group. The SUA levels of the low- and high-dose AD + EMB model groups increased significantly on the 3rd day （P<0.05， P<0.01）， with a persistent increase found in the low-dose AD + EMB model group. Besides， the increase in BUN， KIM-1， and NGAL occurred later （P<0.05， P<0.01）. By contrast， the high-dose AD + EMB model group exhibited a transient increase in SUA. Moreover， the SCr， BUN， KIM-1， and NGAL elevation occurred earlier and were more obvious than those in the low-dose AD + EMB model group （P<0.01）. Remarkable histomorphological abnormalities were detected in the kidney of all model groups， except for the YE+OAPS model group， with the most severe injury present in the high-dose AD+EMB model group. Conclusion:The four models commonly used to screen TCM have their own characteristics. In the four models， the SUA elevation in the HX + OAPS model group and YE + OAPS model group started later， with the mild renal injury observed in the HX + OAPS model group instead of the YE + OAPS model group. The SUA of the low-dose AD + EMB model group increased rapidly and lasted for a long time， accompanied by mild renal injury. The SUA of the high-dose AD + EMB model group only showed a transient increase， accompanied by severe renal injury. The investigation on the characteristics and application of different models and the evaluation of these models based on sensitive and objective indicators are helpful for determining the suitable model for the screening of TCM targeting HUA in the future.

Objective To evaluate the effects of antiretroviral therapy(ART)for the prevention of mother-to-child transmission(PMTCT)of acquired immune deficiency syndrome(AIDS)on the growth and development of 18-month-old children born by human immunodeficiency virus(HIV)-positive pregnant women in Lingshan County,Guangxi Zhuang Autonomous Region,and provide scientific evidence for improving the ART medication plan for PMTCT.Methods Lingshan County,ranking the first in the HIV-epidemic counties of Guangxi,was selected as the research site.According to the design of retrospective case-control study,we assigned all the subjects into the case group and the control group:(1)The case group included the HIV-positive pregnant women who had received ART for PMTCT and their HIV-negative infants in Lingshan County from 2010 to 2017.The historical cards and PMTCT data of them were collected from the national PMTCT database.(2)The control group included the healthy pregnant women and their healthy babies born in the Lingshan Maternity and Infant Hospital in 2017,and the children's growth and development data were collected.The stunted growth in children was defined as at least one of the three main indicators of body height,body weight,and head circumference below the normal range.Results The number of HIV-positive mothers and their infants in the case group was 391 and 368,respectively,and 87.21%(341/391)and 95.38%(351/368)of mothers and infants respectively received ART medication.The HIV positive rate,mortality rate,and mother-to-child transmission rate of 18-month-old children were 1.36%(5/368),4.35%(16/368),and 2.01%(5/249),respectively.The incidence of stunted growth of 18-month-old children in the case group and the control group was 42.12%(155/368)and 23.06%(101/438),respectively,with significant difference(
Case-Control Studies ; China/epidemiology* ; Female ; Growth and Development ; HIV ; HIV Infections/prevention & control* ; Humans ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious/drug therapy* ; Retrospective Studies

OBJECTIVE: To determine the characteristics of postprandial proximal gastric acid pockets (PPGAPs) and their association with gastroesophageal acid reflux in patients with Barrett's esophagus (BE). METHODS: Fifteen patients with BE (defined by columnar lined esophagus of ≥1 cm) and 15 healthy individuals that were matched for age, gender, and body mass index, were recruited. The fasting intragastric pH and the appearance time, length, lowest pH, and mean pH of the PPGAP were determined using a single pH electrode pull-through experiment. For BE patients, a gastroesophageal reflux disease questionnaire (GerdQ) was completed and esophageal 24-h pH monitoring was carried out. RESULTS: The PPGAP was significantly longer (5 (3, 5) cm vs. 2 (1, 2) cm) and the lowest pH (1.1 (0.8, 1.5) vs. 1.6 (1.4, 1.9)) was significantly lower in patients with short-segment BE than in healthy individuals. The PPGAP started to appear proximally from the gastroesophageal pH step-up point to the esophageal lumen. The acidity of the PPGAP was higher in the distal segment than in the proximal segment. In short-segment BE patients, there were significant correlations between the acidity and the appearance time and length of the PPGAP. The length and acidity of the PPGAP were positively associated with gastroesophageal acid reflux episodes. The acidity of the PPGAP was associated with the DeMeester scores, the GerdQ scores, and the fasting intragastric pH. CONCLUSIONS In patients with short-segment BE, a PPGAP is commonly seen. Its length and acidity of PPGAP are associated with gastroesophageal acid reflux, the DeMeester score, and the GerdQ score in patients with short-segment BE.

External attentional focus strategy (EFs) is wildly used for athletes and healthy people to learn motor skills, and is also useful for motor function rehabilitation in patients with neurological disorders. This paper reviewed the concept, theoretical basis and application of EFs in stroke rehabilitation, which is effective on motor function. However, the timing of intervention remains to be further clarified.

Objective:The molecular connectivity index method and total statistical moment method were used to control the quality of traditional Chinese medicine （TCM）， and the stability and consistency of volatile components of Lonicerae Japonicae Flos and Lonicerae Flos were clarified. Method:Volatile oils in Lonicerae Japonicae Flos and Lonicerae Flos from different producing areas was extracted for GC-MS determination with electron bombardment ion source， ion source temperature of 230 ℃， and detection range of m/z 35-650. Then National Institute of Standards and Technology （NIST） 05 and ChemicalBook database were used for qualitative analysis of these volatile components， the peak area normalization method was used for quantitative analysis， and the total statistical moment parameters and the zero-order， first-order， second-order， third-order molecular connectivity indexes of the components were calculated. Result:Number of peaks （RSD were 28.5%， 33.4%， respectively）， total zero-order moments （RSD were 55.5%， 128.9%， respectively） and total second-order moments （RSD were 15.3%， 21.5%， respectively） of 10 batches of Lonicerae Japonicae Flos and Lonicerae Flos were unstable， indicating that the types and contents of volatile components fluctuated sharply， but the total first-order moments （RSD were 7.5%， 8.8%， respectively） and the zero-order， first-order， second-order and third-order molecular connectivity indexes （RSD ranged from 8.1% to 10.3% and 4.2% to 5.5%， respectively） were relatively stable， indicating that the overall "imprinting template" of the components was similar. Statistical analysis of each parameter found that there were no significant differences in the number of peaks， total first-order moments and zero-order， first-order， second-order， third-order molecular connectivity indexes between volatile oils from Lonicerae Japonicae Flos and Lonicerae Flos. Conclusion:Under the guidance of supramolecular gas evolution "imprinting template" theory， the molecular connectivity index method and total statistical moment parameters are used to jointly characterize the "imprinting template" of TCM components in vitro， which can control the stability and consistency of TCM quality.