Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To evaluate the clinical efficacy of intervertebral disc radiofrequency(RF)ablation combined with dorsal medial branch(DMB)neurotomy in elderly patients suffering from chronic low back pain.Methods:A retrospective analysis was conducted on patients aged 60 years and older with chronic low back pain admitted to Beijing Hospital from March 2023 to September 2024.The combined treatment group underwent intervertebral disc radiofrequency ablation combined with radiofrequency treatment of the dorsal medial branch of the spinal nerve.The single treatment group underwent intervertebral disc radiofrequency ablation alone.Pain visual analogue scale(VAS)scores were assessed before treatment and on the first day, 3 months, and 6 months post-treatment.The Oswestry Disability Index(ODI)and Barthel Index were evaluated before treatment and at 3 months and 6 months post-treatment.Clinical efficacy was compared between the two groups.Results:A total of 115 elderly patients with chronic low back pain were enrolled, aged 61 to 72 years(mean 66.5 ± 5.6 years), with 44 males.The combined therapy group consisted of 71 patients, and the monotherapy group consisted of 44 patients.All patients were followed up continuously for 6 months.At all-time points post-treatment, the VAS scores in the combined therapy group were significantly lower than those in the monotherapy group( t=-4.887, -10.095, -7.687, all P<0.05); at 3 and 6 months post-treatment, the combined therapy group showed significantly greater improvements in ODI( t=-3.645, -9.451, both P<0.001)Barthel Index improvement were significantly greater than those in the monotherapy group( t=6.578, 8.530, both P<0.001); the overall good-to-excellent rate in the combined therapy group was 88.7%, higher than the 72.7% in the monotherapy group( χ2=4.85, P<0.05). Conclusions:Combined disc RF ablation and DMB neurotomy provide superior pain relief, functional recovery, and improvement in daily activities compared to single disc ablation in elderly patients with CLBP.This minimally invasive approach represents a safe and effective therapeutic strategy for managing chronic low back pain in the geriatric population.

Objective:To explore the clinical value of computed tomography-three-dimensional(CT-3D)imaging technique in assessing small airway disease(SAD)in children with asthma.Methods:A total of 104 pediatric patients with suspected SAD,who admitted to our hospital from September 2021 to August 2024,were selected,and they were divided into lesion group(48 cases,with obstruction in small airway)and control group(56 cases,lung function without abnormality)according to the results of test for pulmonary function.Both two groups underwent test for lung function and respiratory biphasic CT scan,and the manifestations of high resolution CT(HRCT)image were observed.The correlation between the SAD and the relative indicators of determining ventilation function of lung,which included maximum mid-expiratory flow(MMEF25-75%),forced expiratory flow at 75%vital capacity(FEF75%),forced expiratory flow at 50%vital capacity(FEF 50%),forced expiratory flow at 25%vital capacity(FEF25%)and forced expiratory volume at the first second(FEV1),was analyzed.Results:The MMEF25-75%,FEF75%,FEF50%,FEF25%and FEV1 in the lesion group were significantly lower than those of the control group(t=8.735,12.757,9.724,13.928,10.303,P＜0.05).The incidences of bronchial wall thickening,air retention,Mosaic sign and bronchiole obstruction of HRCT signs of the lesion group were significantly higher than those of the control group(x2=10.715,6.119,6.330,6.587,P＜0.05).Bronchial wall thickening significantly correlated with MMEF25-75%,FEF75%,FEF50%,FEF25%and FEV1(r=-0.360,-0.379,-0.374,-0.367,-0.268,P＜0.001),respectively,and the correlation between it and FEF75%was extremely strong.Air retention significantly correlated with FEF75%and FEV1(r=-0.249,-0.240,P＜0.05),respectively.The Mosaic sign significantly correlated with MMEF25-75%,FEF75%and FEV1(r=-0.236,-0.245,0.257,P＜0.05),respectively.Bronchial obstruction significantly correlated with MMEF25-75%,FEF75%,FEF50%and FEV1(r=-0.248,-0.271,-0.253,-0.275,P＜0.05),respectively.The incidence of asthma in the lesion group was significantly higher than that in the control group(x2=36.783,P＜0.05).Conclusion:The incidence of bronchiolar wall thickening,air retention,Mosaic sign and bronchiolar obstruction of HRCT signs significantly increase in SAD children.They highly correlated with the indicators of ventilation function of lung,especially FEF75%and FEV1,which can reflect the function of small airway at a certain extent.They have great value for identifying early SAD.The application of CT-3D imaging technique in SAD children has a certain of predictive value for the occurrence of asthma.

BACKGROUND: The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD). METHODS: We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships. RESULTS: The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages. CONCLUSIONS: Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit. REGISTRATION No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
Humans ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Dose-Response Relationship, Drug ; Randomized Controlled Trials as Topic

Objective:To evaluate the clinical efficacy of intervertebral disc radiofrequency(RF)ablation combined with dorsal medial branch(DMB)neurotomy in elderly patients suffering from chronic low back pain.Methods:A retrospective analysis was conducted on patients aged 60 years and older with chronic low back pain admitted to Beijing Hospital from March 2023 to September 2024.The combined treatment group underwent intervertebral disc radiofrequency ablation combined with radiofrequency treatment of the dorsal medial branch of the spinal nerve.The single treatment group underwent intervertebral disc radiofrequency ablation alone.Pain visual analogue scale(VAS)scores were assessed before treatment and on the first day, 3 months, and 6 months post-treatment.The Oswestry Disability Index(ODI)and Barthel Index were evaluated before treatment and at 3 months and 6 months post-treatment.Clinical efficacy was compared between the two groups.Results:A total of 115 elderly patients with chronic low back pain were enrolled, aged 61 to 72 years(mean 66.5 ± 5.6 years), with 44 males.The combined therapy group consisted of 71 patients, and the monotherapy group consisted of 44 patients.All patients were followed up continuously for 6 months.At all-time points post-treatment, the VAS scores in the combined therapy group were significantly lower than those in the monotherapy group( t=-4.887, -10.095, -7.687, all P<0.05); at 3 and 6 months post-treatment, the combined therapy group showed significantly greater improvements in ODI( t=-3.645, -9.451, both P<0.001)Barthel Index improvement were significantly greater than those in the monotherapy group( t=6.578, 8.530, both P<0.001); the overall good-to-excellent rate in the combined therapy group was 88.7%, higher than the 72.7% in the monotherapy group( χ2=4.85, P<0.05). Conclusions:Combined disc RF ablation and DMB neurotomy provide superior pain relief, functional recovery, and improvement in daily activities compared to single disc ablation in elderly patients with CLBP.This minimally invasive approach represents a safe and effective therapeutic strategy for managing chronic low back pain in the geriatric population.

Objective:To explore the clinical value of computed tomography-three-dimensional(CT-3D)imaging technique in assessing small airway disease(SAD)in children with asthma.Methods:A total of 104 pediatric patients with suspected SAD,who admitted to our hospital from September 2021 to August 2024,were selected,and they were divided into lesion group(48 cases,with obstruction in small airway)and control group(56 cases,lung function without abnormality)according to the results of test for pulmonary function.Both two groups underwent test for lung function and respiratory biphasic CT scan,and the manifestations of high resolution CT(HRCT)image were observed.The correlation between the SAD and the relative indicators of determining ventilation function of lung,which included maximum mid-expiratory flow(MMEF25-75%),forced expiratory flow at 75%vital capacity(FEF75%),forced expiratory flow at 50%vital capacity(FEF 50%),forced expiratory flow at 25%vital capacity(FEF25%)and forced expiratory volume at the first second(FEV1),was analyzed.Results:The MMEF25-75%,FEF75%,FEF50%,FEF25%and FEV1 in the lesion group were significantly lower than those of the control group(t=8.735,12.757,9.724,13.928,10.303,P＜0.05).The incidences of bronchial wall thickening,air retention,Mosaic sign and bronchiole obstruction of HRCT signs of the lesion group were significantly higher than those of the control group(x2=10.715,6.119,6.330,6.587,P＜0.05).Bronchial wall thickening significantly correlated with MMEF25-75%,FEF75%,FEF50%,FEF25%and FEV1(r=-0.360,-0.379,-0.374,-0.367,-0.268,P＜0.001),respectively,and the correlation between it and FEF75%was extremely strong.Air retention significantly correlated with FEF75%and FEV1(r=-0.249,-0.240,P＜0.05),respectively.The Mosaic sign significantly correlated with MMEF25-75%,FEF75%and FEV1(r=-0.236,-0.245,0.257,P＜0.05),respectively.Bronchial obstruction significantly correlated with MMEF25-75%,FEF75%,FEF50%and FEV1(r=-0.248,-0.271,-0.253,-0.275,P＜0.05),respectively.The incidence of asthma in the lesion group was significantly higher than that in the control group(x2=36.783,P＜0.05).Conclusion:The incidence of bronchiolar wall thickening,air retention,Mosaic sign and bronchiolar obstruction of HRCT signs significantly increase in SAD children.They highly correlated with the indicators of ventilation function of lung,especially FEF75%and FEV1,which can reflect the function of small airway at a certain extent.They have great value for identifying early SAD.The application of CT-3D imaging technique in SAD children has a certain of predictive value for the occurrence of asthma.

ObjectiveTo observe the clinical effectiveness and safety of Xuandi Ziyin Mixture （玄地滋阴合剂） for central precocious puberty （CPP） in girls with syndrome of yin deficiency and fire exuberance， and to analyse the effect of body mass index （BMI） on the effectiveness. MethodsA total of 236 girls with CPP of yin deficiency and fire exuberance syndrome were included， and all of them were given Xuandi Ziyin Mixture， 30 ml each time， twice a day， for a total treatment period of 6 months. Before and after treatment， children's weight， height and bone age were measured， BMI and BMI Z-score （BMI Z） and the difference between bone age and actual age were calculated； ultrasound was used to detect uterine and ovarian sizes， and to calculate uterine volume （V_uterus）， bilateral ovarian volume （V_{left ovary}， V_{right ovary}）， and bilateral maximal follicle diameters （r_{left follicle} and r_{right follicle}）； and serum sex hormones were measured， including follicle-stimulating hormone （FSH）， luteinising hormone （LH）， prolactin （PRL）， estradiol （E₂）， and testosterone （T）， and were scored for traditional Chinese medicine （TCM） syndrome. Multiple linear regression was used to analyse the influence factors of the difference between bone age and actual age， and changes in uterine volume. The children were divided into the normal weight group and the overweight/obesity group according to baseline BMI， and the bone age， the difference between bone age and actual age， V_uterus and BMI Z scores before and after treatment were compared between the two groups. ResultsFinally， 199 children entered the statistical analysis. Compared with pre-treatment， the bone age， BMI and BMI Z scores of the children increased after treatment， and the difference between bone age and actual age， TCM syndrome scores， V_uterus， V_{left ovary}， V_{right ovary}， r_{left follicle} and r_{right follicle} decreased； and the levels of serum FSH， LH， E₂， and T significantly decreased （P＜0.05 or P＜0.01）. The difference between bone age and actual age was negatively correlated with LH and V_uterus （P＜0.05）， and changes in uterine volume were positively correlated with LH （P＜0.01）. Comparing between the groups before and after treatment， the bone age， difference between bone age and actual age， and BMI Z scores of children in the normal weight group （100 cases） were significantly smaller than those in the overweight/obesity group （99 cases） （P＜0.01）. Compared with pre-treatment， the bone age of the children in both groups increased， but the difference between bone age and actual age and V_uterus were significantly smaller （P＜0.01）. Further comparison of Δ bone age and actual age difference and ΔV_uterus （Δ = post-treatment value - pre-treatment value） between the two groups showed no statistically significant difference （P＞0.05）. ConclusionsXuandi Ziyin Mixture can reduce bone age， sex hormone level， ovary and uterus size， and improve clinical symptoms in girls with yin deficiency and fire exuberance syndrome of CPP. It is also effective in overweight/obese children， and the inhibitory effect on bone age in girls with CPP is not affected by BMI， with good safety.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.