OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

AIM To identify the chemical components of Longmu Qingxin Mixture by UPLC-Q-TOF-MS and study its material basis for the treatment of attention deficit hyperactivity disorder.METHODS The sample was detected by mass spectrometry in positive and negative ion mode on a Waters CORTECS? UPLC? T3 chromatographic column.The data were analyzed with Peakview 1.2 software and matched with the Natural Products HR-MS/MS Spectral Library 1.0 database,and the components were identified in combination with literature reports.The material basis of Longmu Qingxin Mixture for the treatment of attention deficit hyperactivity disorder was analysed according to the identified components.RESULTS Forty chemical components were identified,including 11 flavonoids,6 monoterpene glycosides,4 triterpene saponins,3 phenolic acids,6 alkaloids etc.,which mainly derived from Radix Astragali,Radix Paeoniae Alba,Radix Scutellariae,licorice root,Ramulus Uncariae cum,etc.,baicalein,formononetin,astragaloside Ⅳ and rhynchophylline may be the material basis for the therapeutic effect of Longmu Qingxin Mixture.CONCLUSION UPLC-Q-TOF-MS can quickly identify the chemical components of Longmu Qingxin Mixture.Flavonoids,triterpene saponins and alkaloids may be the material basis for Longmu Qingxin Mixture for the treatment of attention deficit hyperactivity disorder,which can provide the basis for its material basis research,quality standard establishment and pharmacological study of the dismantled formula.

Objective:To compare the clinical effects of different combinations of anesthetics in transperineal prostate biopsy in elderly male patients.Methods:We randomly divided 132 ≥65-year-old male patients to receive transperineal prostate biopsy under combined intravenous anesthesia with propofol+sufentanil(the PS group),remimazolam+sufentanil(the RS group),propofol+alfentanil(the PA group),or remimazolam+alfentanil(the RA group).We recorded the mean arterial pressure(MAP)and heart rate(HR)of the patients,the required rescue sedation,the Richmond Agitation-Sedation Scale(RASS)scores upon admission into the postanesthesia care unit(PACU)after surgery,the length of stay in the PACU and the incidence of adverse reactions,followed by comparison of the data obtained among the four groups.Results:Operations were successfully completed in all the patients.At 5 moment points from T3 to t2,RA and RS groups had less effect on MAP than PA and PS groups(P＜0.05);at 5 moment points from Tl to T5,RA and RS groups had less effect on HR than PA and PS groups(P＜0.05),and this effect was more obvious in RA group than in RS group.During anesthesia-induction,the incidence rate of injection pain was remarkably lower in the RA and RS than in the PA and PS groups(P＜0.05),and that of respiratory depression was higher in the PS than in the other three groups(P=0.013).The RASS scores were significantly higher(P＜0.05)and the PACU stay shorter in the RA and RS than in the PA and PS groups(P＜0.05).Dramatically more cases of intraoperative body movement and remedial medication requirement were observed in the former than in the latter two groups(P=0.013),but there was no statistically significant difference in the dose of remedial medi-cation between the four groups of patients(P＞0.05).Conclusion:For elderly male patients undergoing transperineal prostate bi-opsy under intravenous anesthesia with preservation of spontaneous breathing,the combined use of remimazolam and alfentanil can a-chieve more stable intraoperative hemodynamics,faster recovery from anesthesia and a lower incidence of perioperative adverse reac-tions,and produce an even better anesthetic effect with a small dose of propofol to suppress the body movement at the time of needle puncture.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

ObjectiveTo preliminarily predict the active components， action targets， and signaling pathways of Arnebia euchroma in the treatment of melanoma based on network pharmacology and molecular docking， and to verify its possible mechanism of action in in vitro experiments. MethodThe active components and related targets of A. euchroma were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）SwissTargetPrediction and literature， and the targets related to melanoma from the GeneCards， Online Mendelian Inheritance in Man （OMIM）， and Comparative Toxicogenomics Database （CTD）. Following the construction of the protein-protein interaction （PPI） network of active components and related targets of A. euchroma and melanoma-related targets using STRING， Cytoscape 3.8.2 was used for screening and analyzing the nodes in the network of A. euchroma against melanoma. The intersections were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis using DAVID 6.8. Acetyl alkannin， the active component in A. euchroma， was docked to the target by AutoDock Vina 1.1.2. The in vitro experiments were then carried out to verify the anti-melanoma effect of A. euchroma. ResultA total of 271 common targets of A. euchroma and melanoma were harvested， among which 23 were key targets， including matrix metalloproteinase-9 （MMP-9） and Janus kinase 2 （JAK2）. As revealed by KEGG enrichment analysis， A. euchroma mainly acted on Janus kinase/signal transduction and activator of transcription （JAK/STAT）， tyrosine kinase receptor （ErbB）， and vascular endothelial growth factor （VEGF） signaling pathways to resist melanoma. According to molecular docking， acetyl alkannin exhibited a good docking activity with JAK2， STAT3， VEGF， MMP-9， and E-cadherin receptors. The results of Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） showed that acetyl alkannin at different doses inhibited the protein and gene expression of JAK2， STAT3， VEGF， MMP-9， and E-cadherin in A375 cells （P<0.05）. ConclusionA. euchroma alleviates melanoma via multiple targets and multiple pathways， and it may exert the therapeutic effects by affecting the expression of such key target proteins as JAK2， STAT3， VEGF， MMP-9， and E-cadherin and inhibiting the invasion and metastasis of melanoma cells. This study has provided an experimental basis for the treatment of tumor with A. euchroma.

Objective: The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. Methods: A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Results: Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Conclusions Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.
COVID-19/complications* ; Follow-Up Studies ; Humans ; Olfaction Disorders/etiology* ; Pandemics ; Prospective Studies ; SARS-CoV-2

Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.
Blood-Brain Barrier ; Brain ; Central Nervous System Diseases ; Humans ; Medicine, Tibetan Traditional ; Stroke/drug therapy*

The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.
Acetaminophen/toxicity* ; Animals ; Antioxidants/pharmacology* ; Glutamate-Cysteine Ligase/pharmacology* ; Glutathione ; Interleukin-6/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Liver ; Medicine, Tibetan Traditional ; Mice ; NF-E2-Related Factor 2/metabolism* ; NF-kappa B/metabolism* ; RNA, Messenger/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.
Aluminum Chloride/adverse effects* ; Alzheimer Disease/drug therapy* ; Animals ; Galactose/metabolism* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Hippocampus/metabolism* ; Mice ; Mice, Inbred BALB C ; Plant Extracts ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; tau Proteins