Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

Objective To analyze the influence of midazolam and propofol on sedation effect and blood gas indicators in elderly patients undergoing mechanical ventilation after cardiopulmonary bypass(CPB)cardiac surgery.Methods The elderly patients with mechanical ventilation after CPB cardiac surgery were grouped according to cohort method,including midazolam group(group M),propofol group(group P)and midazolam-propofol combined administration group(group M-P).Group M was treated with midazolam(intravenous injection of 0.05-0.10 mg kg-1 midazolam for sedation induction,and then continuously intravenous injection of 0.05-0.15 mg·kg-1·h-1 midazolam by micropump),and group P was treated with propofol(intravenous injection of 0.5 mg·kg-1 propofol for sedation induction,and then continuously intravenous injection of 0.5-2.0 mg·kg-1·h-1 propofol by micropump),and group M-P was given combined administration of midazolam and propofol(intravenous injection of 0.02-0.05 mg·kg-1 midazolam and 0.2-0.5 mg·kg-1 propofol for sedation induction and then continuously intravenous pump of 0.05-0.1 mg·kg-1 midazolam and 0.5-0.8 mg·kg·h-1 propofol).The sedation effect,blood gas indicators,hemodynamic indicators,extubation time,intensive care unit(ICU)stay time and treatment cost were compared among the three groups,and the adverse drug reactions during sedation therapy were recorded.Results There were 43 cases in group M,44 cases in group P,39 cases in group M-P.The drug onset times in groups M,P and M-P were(77.94±12.05),(18.18±5.20)and(21.25±9.36)s;the times to achieve satisfactory sedation effect were(42.57±11.41),(22.63±8.17)and(23.98±10.25)min;the recovery times after withdrawal were(59.30±14.86),(19.83±5.44)and(22.16±6.29)min;the extubation times were(1.61±0.20),(1.45±0.22)and(1.37±0.15)d;the ICU stay times were(2.17±0.29),(1.91±0.36)and(1.84±0.25)d;the treatment costs were(186.59±60.83),(922.97±164.34)and(375.03±71.16)thousand yuan;and the total incidence rates of adverse drug reactions were 34.88％,4.55％and 7.69％respectively,all with significant difference(all P＜0.05).There were no statistically significant differences in mean arterial pressure(MAP),heart rate(HR),oxygen saturation(SpO2),partial pressure of oxygen(PaO2),partial pressure of carbon dioxide(PaCO2)at T0,T1,T2,T3 and T4 among the three groups(all P＞0.05).Conclusion Combined administration of midazolam and propofol in elderly patients underwent mechanical ventilation after CPB cardiac surgery has a significant sedation effect,and it is conducive to reducing the dosages of sedative drugs,and it has small impact on blood gas indicators and hemodynamic indicators of patients.Compared with midazolam alone,it is more beneficial to shortening the extubation time and ICU stay and reducing the total incidence rate of adverse drug reactions,and compared with propofol alone,it is more beneficial to reducing treatment cost,and is a more ideal sedation administration model.

Aprocitentan is a dual endothelin receptor antagonist.Based on the effective evidence of Ⅲ phases of clinical trials,the drug was approved for marketing by the U.S.Food and Drug Administration on March 19,2024 for the treatment of refractory hypertension.At present,multiple clinical studies have confirmed that Aprocitentan has excellent antihypertensive effects and good tolerability.This article reviews the pharmacological effects,preclinical.

Objective To investigate the bacterial community diversity in Dermatophagoides farinae. Methods Laboratory-cultured D. farinae was collected, and the composition of microbial communities was determined by sequence analyses of the V4 region in the bacterial 16S ribosomal RNA (16S rRNA) gene on an Illumina PE250 high-throughput sequencing platform. Following quality control and filtering of the raw sequence files, valid reads were obtained and subjected to operational taxonomic units (OTU) clustering and analysis of the composition of microbial communities and alpha diversity index using the Usearch software, Silva database, and Mothur software. Results A total of 187 616 valid reads were obtained, and 469 OTUs were clustered based on a sequence similarity of more than 97%. OTU annotation showed that the bacteria in D. farinae belonged to 26 phyla, 43 classes, 100 orders, 167 families and 284 genera. The bacteria in D. farinae were mainly annotated to five phyla of Proteobacteria, Firmicutes, Bacteroidota, Actinobacteriota, and Acidobacteriota, with Proteobacteria as the dominant phylum, and mainly annotated to five dominant genera of Ralstonia, norank-f-Mitochondria, Staphylococcus and Sphingomonas, with Wolbachia identified in the non-dominant genus. Conclusions A high diversity is identified in the composition of the bacterial community in D. farinae, and there are differences in bacterial community diversity and abundance among D. farinae.

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.
Alanine Transaminase ; Antiviral Agents/therapeutic use* ; DNA, Viral ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic ; Humans ; Retrospective Studies ; Tenofovir/therapeutic use* ; Treatment Outcome

Background: A patient’s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. Methods: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients’ oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. Results: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0–62.0) years were analyzed. After in-hospital treatment, patients’ inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0–11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients’ stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0–16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0–4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients’ urine specimens after throat swabs were negative. Using a multiple linear regression model (F=2.669, P=0.044, and adjusted R²=0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’ stools (t=-2.699, P=0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs 8.0 days, respectively; t=2.550, P=0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs 11 days, respectively; t=4.631, P <0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P >0.05). Conclusions In brief, as the clearance of viral RNA in patients’ stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.
Adult ; Aged ; Betacoronavirus ; genetics ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; genetics ; rehabilitation ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; genetics ; rehabilitation ; RNA, Viral ; genetics ; Real-Time Polymerase Chain Reaction ; Retrospective Studies

Coronary Artery Bypass ; adverse effects ; Female ; Humans ; Male ; Mammary Arteries ; injuries

Objective The aim of this work was to study whether PM2. 5 induces oxidative stress and histopatholog-ical changes in uterine tissue of rats. Methods Thirty 4-week-old female Sprague-Dawley rats were randomly divided into the control group (normal saline), the low dose of PM2.5 group (1. 5 mg/kg) and the high dose of PM2.5 group (37. 5 mg/kg) . After exposed to PM2. 5 for 10 days, the rats were sacrificed to examine the histopathological changes in uterine tissues using H&E staining. The contents of SOD, GSH, MDA and LDH were also determined in the uterine tissues. Results Compared with the control group, PM2. 5 caused changes in the uterine structure, showing a thinner endometrial epithelium and reduction of stromal cells and blood vessels. The assessment of oxidative stress parameters showed that the levels of MDA and LDH in the high dose group were (6. 53 ± 1. 24) nmol/mg prot and (265. 62 ± 24. 65) U/g prot, significantly higher than those in the control group ( P<0. 05 ) . Compared with the control group, the levels of SOD and GSH in the high dose and low dose groups were significantly decreased (P<0. 05). Conclusions PM2.5 exposure can cause damages in the rat uterus by inducing oxidative stress.