Association between thyroid function and prognosis of severe COVID-19 among patients with SARS-CoV-2 infection: a retrospective cohort study in China.

Objective: This study aims to examine the thyroid hormone profile and its association with severe coronavirus disease 2019 (COVID-19) in patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This retrospective cohort study enrolled patients admitted to a tertiary hospital due to SARS-CoV-2 infection between February 18 and May 18, 2022. Clinical data were collected retrospectively from the electronic medical record system. Based on the thyroid function, patients were divided into five groups: normal, non-thyroid illness syndrome (NTIS), hypothyroidism, thyrotoxicosis, and unclassified. The association between thyroid function and severe COVID-19 was detected using multivariable logistic regression and restricted cubic splines analysis. Results: This study included 3,161 patients, with 7.7% of them developing severe COVID-19. 44.9% of the patients had normal thyroid function, 36.5% had NTIS, 6.7% had hypothyroidism, and 1.0% had thyrotoxicosis on admission. After adjusting for age, sex, and relevant clinical characteristics, NTIS and hypothyroidism were associated with increased risks of severe COVID-19 (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.59-3.56 and OR 2.29, 95% CI 1.23-4.26, respectively), compared to normal thyroid function group. Among patients with NTIS or hypothyroidism, higher levels of total triiodothyronine (TT3) are associated with lower risks of severe COVID-19 (OR 0.73, 95% CI 0.64-0.82, for every 0.1nmol/L increase in TT3 level). Conclusion: Thyroid hormone profiles of NTIS or hypothyroidism are associated with increased risks of severe COVID-19. The decreased level of TT3 correlated with the increased risk of severe COVID-19 in patients with NTIS or hypothyroidism.

Effects of low-frequency pulsed electrical stimulation at the common peroneal nerve on chronic refractory wounds of the lower limb: A randomized controlled trial.

Background and aims: Electrical stimulation (ES) has been shown to substantially enhance the quality of life by alleviating pain in patients with chronic wounds. This study aimed to observe the effects of low-frequency pulsed wearable ES at the common peroneal nerve on chronic refractory wounds of the lower limb. Methods: Forty-eight participants were randomly divided into control group (n = 24) and treatment group (n = 24) in this study. The control group received standard wound care (SWC) exclusively, whereas the treatment group was administered both SWC and the wearable low-frequency ES targeting the common peroneal nerve. Measurements of wound area, pain intensity, wound status, and quality of life scores were systematically recorded both before and after 4 weeks treatment. Results: After 4 weeks of intervention, the percentage area reduction was significantly higher in the treatment group compared to the control group (Z = -3.9, p < 0.001), and the healing rate of the treatment group was significantly higher than that of the control group (33% vs. 4%). Moreover, the visual Analog Scale for Pain score (ß = -0.65, p = 0.019), the Bates-Jensen Wound Assessment Tool score (p < 0.05), and the questionnaire on quality of life with chronic wounds (Wound-Qol) score (ß = -4.23, p = 0.003) were significantly decreased in the patients in the treatment group compared to the control group. Conclusion: The wearable low-frequency pulsed ES at the common peroneal nerve for the treatment of chronic refractory wounds showed significant improvement and were far superior compared to SWC. Future research should broaden its scope to include a diverse range of wound types and benefit from collaboration across multiple research centers.

Evaluation of the community involvement of nursing experts in reducing unintentional injuries in children.

BACKGROUND: Nursing experts regularly visited the community to deliver safety education on the prevention of unintentional injuries in children to the parents of children aged 0-6 years and to pregnant women in a maternity school. This was undertaken to explore the effects of the measure on preventing unintentional injuries in children in Chizhou, China. METHODS: Using the convenience sampling method, the guardians(it means mother in this study)of children were investigated. The nursing experts visited communities in which the number of nursing experts is declining. Data on unintentional injuries in children in the previous year were collected retrospectively. RESULTS: After the nursing experts delivered safety education to the community, the scores of the questionnaire on unintentional injury prevention knowledge completed by children's guardians increased significantly (p < 0.01). Among the children whose guardians completed the questionnaire, there were 157 cases of unintentional injury in 2020 and 103 cases in 2021 (p < 0.05). The types of unintentional injuries included scratches, falls, sharp object injuries, swallowing of foreign bodies, burns and traffic accidents; there was no statistical difference (p > 0.05). However, there were significant differences in terms of gender ratio and location (p < 0.05). CONCLUSION: In conjunction with the maternity school for pregnant women and the vaccination programme, nursing experts delivered safety education regarding unintentional injuries in children; this may have promoted safety and protection awareness in the children's guardians and reduced unintentional injuries.

Phase I, First-in-Human, Single and Multiple Ascending Dose- and Food-Effect Studies to Assess the Safety, Tolerability and Pharmacokinetics of a Novel Anti-hepatitis B Virus Drug, Bentysrepinine (Y101), in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVE: Bentysrepinine (Y101), a derivative of repensine (a compound isolated from Dichondra repens Forst), is a novel phenylalanine dipeptide currently under development for the treatment of hepatitis B virus (HBV). The objectives of these studies were to assess the safety, tolerability and pharmacokinetics of bentysrepinine in healthy Chinese subjects. METHODS: Two randomised, double-blind, placebo-controlled trials evaluated a single oral dose (50-900 mg, study 01) and multiple doses (300 mg and 600 mg, study 02), and a randomised, open, crossover food-effect study (600 mg, study 03) of bentysrepinine was established. Safety and tolerability were assessed by adverse event (AE) reporting, clinical laboratory tests, physical examinations, vital sign monitoring and electrocardiogram (ECG). Plasma, urine and faecal samples were analysed using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods to investigate the pharmacokinetics of bentysrepinine. RESULTS: Ninety-four subjects were enrolled, and bentysrepinine was well tolerated. Mild and reversible AEs occurred for single and multiple oral doses between 50 and 900 mg. The most common adverse effects were increased alanine aminotransferase (ALT) and aspartate transaminase (AST). Other clinically significant AEs included nausea and elevated urine leukocytes, urine red blood cells, transaminase, creatine kinase, total cholesterol, triglycerides, and low-density cholesterol. There were no clinically significant changes in the ECG, vital signs or laboratory assessments during the studies. The maximum tolerated dose (MTD) was not reached in the dose escalation study. Bentysrepinine was rapidly absorbed and metabolised with a mean time to reach maximum concentration (Tmax) between 1-2 h and a mean terminal elimination half-life (t1/2) of approximately 1-3 h. In the single ascending dose study, the exposure including the area under the concentration-time curve (AUC) and the maximum plasma concentration (Cmax) of bentysrepinine generally increased in a dose-dependent but not dose-proportional manner in the 50-900 mg dose range. The urinary excretion and faecal excretion of unchanged bentysrepinine were 2.98% and 4.58% of the total dose, respectively. In the multiple-dose study, no accumulation was found after repeated administration at the 300 mg and 600 mg dose levels. The food-effect study using a 600 mg single dose showed that food intake has an obvious effect on the absorption of bentysrepinine from tablets. No experimental differences were found based on sex. CONCLUSION: Bentysrepinine exhibited acceptable safety and tolerability in healthy subjects in the dose range of 50-900 mg in both single- and multiple-dose studies. The drug did not exhibit linear pharmacokinetic characteristics. No accumulation was observed after the administration of multiple 300 and 600 mg doses. Bentysrepinine is extensively metabolised in the body. Food may increase its bioavailability. TRIALS REGISTRATION: CFDA registration numbers CTR20160096, CTR20160094, and CTR20140543 (www.chinadrugtrials.org.cn).

Study on Drug-Drug Interactions Between Chiglitazar, a Novel PPAR Pan-Agonist, and Metformin Hydrochloride in Healthy Subjects.

Chiglitazar (CHI) is a potent and selective peroxisome proliferator-activated receptor potentially for the treatment of patients with type 2 diabetes mellitus (T2DM). An open-label, randomized, 3-period crossover and self-controlled study was conducted to investigate drug-drug interaction potential between CHI and metformin hydrochloride (MET). Eligible subjects received a single oral dose of CHI (48 mg), MET (1000 mg), or a combination in each period, followed by serial blood sampling collected for up to 48 hours postdose, and safety was assessed throughout the trial. The area under the plasma concentration-time curves from time 0 to 48 hours (AUC0-48 h ) of CHI was similar following administration alone or with MET (AUC0-48h , 12 540 ng·h/mL [9811-15 269 ng·h/mL] vs 12 130 ng·h/mL [9304-14 956 ng·h/mL]; 90% confidence interval [CI] of its geometric mean ratio [GMR], 89.7%-103.8%), whereas the maximum concentration (Cmax ) of CHI was reduced during coadministration, as its 90%CI of the GMR was slightly outside the acceptance range for bioequivalence (Cmax , 1620 ng/mL [1418-1822 ng/mL] vs 1420 ng/mL [1049-1791 ng/mL], 90%CI GMR, 77.%-94.1%). However, it was not considered clinically meaningful. The MET exposures remained consistent in the absence or presence of CHI (AUC0-48 h , 12 570 ng·h/mL [10681-14 459 ng·h/mL] vs 13 190 [10973-15 407 ng·h/mL); 90%CI of GMR: 99.1%-110.5%; Cmax , 1790 ng/mL [1448-2132 ng/mL] vs 1820 ng/mL [1510-2130 ng/mL]; 90%CI of GMR, 94.2%-110.9%). No moderate to severe adverse events were reported. Our study indicated no clinically significant pharmacokinetic drug-drug interaction between CHI and MET and demonstrated good tolerance in subjects. These results support future application of CHI in combination with MET for treatment of T2DM.

[Preventing laryngeal anterior commissure adhesion after operation: a study in canines].

OBJECTIVE: To explore the better operational methods by the laser surgery to treat diseases involving the laryngeal anterior commissure. It can excise the diseases as well as avoid anterior commissure adhesion, laryngostenosis and dyspnea after operations. METHOD: Twelve dogs were divided into 4 groups at random. There were three dogs in one group. A: excising experimental dog's anterior commissure by twice operations, the interval time was two weeks; B: excising experimental dog's anterior commissure in one time, at the same time suturing the silica gel sheet on the anterior commissure; C: excising experimental dog's anterior commissure in one time and then applying MMC on the wound of the anterior commissure; D: excising experimental dog's anterior commissure in one time, without any treatment. RESULT: All of the dog's surgery were completed successfully by laser. Four weeks later, we observed the raw surfaces. A: the neonatal membrane covered the wound, inflammatory reaction slight, we could not see obvious adhesion in the anterior commissure. B: the membrane covered the wound, appearing the dark chronic inflammation, we could see the adhesion in the anterior commissure slight. C: the membrane covered the wound, edematization, we could see the moderate adhesion in the anterior commissure. D: edematization, we could see the adhesion in the anterior commissure obviously. Four groups were all appeared hoarsenesses, the most slightly in group A, secondly in B and C, the worst in D. The analysis of vocal cord length of 4 groups, we used matched-pairs t-test, A, B, C groups' P>0.05, the vocal cord length didn't become shorter than before obviously. Group D's P<0.01, that meant the vocal cord length became shorter obviously. Between each group,we used reiterature-measurement analysis of variance (P<0.05), the change of vocal cord length had disparity in different groups. The comparison in two groups suggested that group A is the best. B and C are inferior ,but no disparity between them. The analysis of glottis area of 4 groups, as the same method above, A,B groups' P>0.05, the glottis area didn't shrink than before obviously. C and D groups' P<0.05, that meant having statistical significance and glottis area shrinked obviously. Between each group, we used reiterature-measurement analysis of variance (P>0.05), we could not think that the changes of four groups have disparity. CONCLUSION: Excising the experimental dog's anterior commissure by laser, compared the 4 different operation methods, group A is the best method. B and C are inferior. The results are valuable in clinic when we perform operations by laser to treat the disease involving the anterior commissure.