To observe the clinical efficacy and safety of tacrolimus ointment combined with dupilumab injection in treatment of adult atopic dermatitis (AD).

Adult patients with AD in the Affiliated Hospital of Xuzhou Medical University were enrolled as study subjects. The control group was treated with tacrolimus ointment (external use, twice a day) + ebastine tablets (oral administration, 10 mg·times^-1·d^-1), and the observation group received tacrolimus ointment + ebastine tablets + dupilumab injection (subcutaneous injection, initial dose of 600 mg, followed by 300 mg·times^-1, once every two weeks). The clinical efficacy, skin barrier indicators, serum thymic stromal lymphopoietin (TSLP) and interleukin-31 (IL-31) were compared between the two groups, and the safety was assessed.

A total of 140 cases (80 cases in control group and 60 cases in observation group) were screened in this study. 48 pairs were successfully matched by the propensity matching score method according to the ratio of 1∶1. Finally, 48 cases in control group and 48 cases in observation group were included. After 4 weeks of treatment, the effective rate in observation group was 93.75% (45 cases/48 cases), which was significantly higher than 79.17% (38 cases /48 cases) in control group (P<0.05). the scoring atopic dermatitis (SCORAD) scores in observation and control groups were (15.56±3.33) and (21.50±3.51) points, and the investigator global assessment (IGA) scores were (1.98±0.57) and (2.25±0.44) points, and pruritus index (NRS) scores were (2.85±0.58) and (3.19±0.49) points, and dermatological life quality index (DLQI) scores were (10.04±1.03) and (10.88±1.16) points, and AD disease control (ADCT) scores were (7.00±0.29) and (7.17±0.43) points, respectively. The transdermal water loss (TEWL) values in observation group and control group were (13.17±2.37) g·m^-2·h^-1 and (15.35±3.21) g·m^-2·h^-1, and skin moisture contents were (26.46±4.68)% and (22.23±5.10)%, and sebum contents were (89.79±3.44) μg·cm^-2 and (80.31±3.73) μg·cm^-2, respectively. Serum TSLP levels in observation group and control group were (138.81±14.79) pg·mL^-1 and (148.30±16.23) pg·mL^-1, and serum IL-31 levels were (74.63±9.42) pg·mL^-1 and (85.34±10.18) pg·mL^-1, respectively, and the above indicators in observation group were statistically significantly different compared with those in control group (all P<0.05). During treatment, the adverse drug reactions in observation group were conjunctivitis, edema, diarrhea, swelling and pain at the injection site, and the adverse drug reactions in control group were nausea and edema, and there was no statistical significantly differences in the total incidence rate of adverse drug reactions between groups (P>0.05).

Combination of dupilumab injection on the basis of tacrolimus ointment and ebastine tablets has a significant clinical effect in the treatment of AD, and it can statically significantly improve the symptoms and skin barrier, and reduce the levels of serum TSLP and IL-31.

To explore the value of texture features in magnetic resonance imaging (MRI) for predicting post-stroke cognitive impairment (PSCI) in elderly patients, and to analyze its correlation with the efficacy of PSCI drug therapy, providing a basis for selecting the timing and optimizing clinical drug intervention plans.

A retrospective analysis was conducted on the data of stroke patients admitted from January 2020 to January 2024. The data was divided into a training set (n=160) and a validation set (n=56) according to the data source. Collect PSCI standardized medication treatment data (including cholinesterase inhibitors, memantine, and combination therapy regimens) for all patients from baseline to cognitive assessment. After preprocessing of T1 weighted imaging (T1w) images, texture features were measured in the hippocampus and entorhinal cortex. Patients with high hippocampal kurtosis (≥ 2.5) and low hippocampal kurtosis were grouped and analyzed. A PSCI prediction and efficacy prediction model was constructed and validated based on drug treatment information. As a result, a total of 327 patients were included in this study, including 211 males and 116 females. The accuracy of the prediction model in the training set and validation set is 90% and 77%, respectively; Covariance analysis showed that there were differences (P<0.05) in hippocampal kurtosis, entorhinal cortex kurtosis, and entorhinal cortex deficit anomaly (IDM) between PSCI patients and non PSCI patients. The effective rate of donepezil treatment showed that the group with high hippocampal kurtosis was significantly higher than the group with low kurtosis (76.31% vs. 41.22%, P<0.01); Patients with IDM ≥ 0.4 in the entorhinal cortex showed better efficacy with combination therapy (donepezil+memantine) compared to monotherapy (82.13% vs. 58.28%, P<0.05). After optimizing the model and incorporating drug treatment factors, the validation set AUC increased to 0.82.

Conventional clinical MRI texture features are reliable early predictors of PSCI and are significantly associated with the efficacy of PSCI drug therapy. They can be combined with drug therapy information to construct more accurate prediction and efficacy evaluation models, providing imaging support for individualized drug intervention in PSCI.

To investigate the effects of andrographolide on microRNA (miR) -218-5p/RY box transcription factor 5 (SOX5) on the proliferation, invasion and epithelial mesenchymal transformation (EMT) of oral squamous cell carcinoma cells.

CAL-27 cells were divided into the following groups: blank group (conventional culture), andrographolide group (treated with 15 μmol·L^-1 andrographolide), andrographolide + inhibitor NC group (treated with 15 μmol·L^-1 andrographolide and transfected with inhibitor NC), andrographolide + miR-218-5p inhibitor group (treated with 15 μmol·L^-1 andrographolide and transfected with miR-218-5p inhibitor), andrographolide + miR-218-5p inhibitor + si-NC group (treated with 15 μmol·L^-1 andrographolide and co-transfected with miR-218-5p inhibitor and si-NC), and andrographolide + miR-218-5p inhibitor + si-SOX5 group (treated with 15 μmol·L^-1 andrographolide and co-transfected with miR-218-5p inhibitor and si-SOX5). The relative expression levels of miR-218-5p and SOX5 mRNA were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), cell proliferation ability was measured using the 5-ethynyl-2′-deoxyuridine (EdU) assay, cell invasion ability was assessed by Transwell assay, and the relative expression levels of EMT-related proteins were determined by Western blotting.

After different treatment periods, the relative expression levels of miR-218-5p in blank group, andrographolide group, andrographolide + inhibitor NC group and andrographolide + miR-218-5p inhibitor group were 1.00±0.11, 2.76±0.48, 2.69±0.50 and 1.19±0.17, respectively; the relative expression levels of SOX5 mRNA were 1.00±0.09, 0.36±0.07, 0.35±0.05 and 0.93±0.18, respectively. Compared with the blank group, the andrographolide group showed statistically significantly upregulated miR-218-5p relative expression levels and statistically significantly reduced SOX5 mRNA relative expression levels (all P<0.05). The proliferation rates in blank group, andrographolide group, andrographolide + inhibitor NC group, andrographolide + miR-218-5p inhibitor group, andrographolide + miR-218-5p inhibitor + si-NC group and andrographolide + miR-218-5p inhibitor + si-SOX5 group were (62.76±8.14)%, (23.58±2.87)%, (25.12±3.64)%, (51.29±9.12)%, (50.76±8.29)% and (34.18±6.83)%, respectively; the number of invasive cells were (154.23±17.24), (67.13±9.37), (72.81±11.28), (125.36±18.74), (118.15±19.80) and (80.44±12.13), respectively; the relative expression levels of E-cadherin were 1.00±0.12, 2.62±0.43, 2.56±0.47, 1.47±0.27, 1.51±0.23 and 2.24±0.43, respectively; the relative expression levels of N-cadherin were 1.00±0.11, 0.41±0.08, 0.39±0.06, 0.83±0.17, 0.86±0.15 and 0.51±0.10, respectively; the relative expression levels of Vimentin were 1.00±0.08, 0.49±0.07, 0.46±0.09, 0.85±0.16, 0.88±0.17 and 0.55±0.11, respectively. Compared with blank group, andrographolide group showed statistically significantly decreased proliferation rate, number of invasive cells and relative expression levels of N-cadherin and Vimentin, while demonstrating statistically significantly increased relative expression levels of E-cadherin (all P<0.05).

Andrographolide inhibits the proliferation, invasion, and EMT in oral squamous cell carcinoma, potentially through upregulating miR-218-5p and subsequently targeting the suppression of SOX5 expression.

This current study was conducted in healthy Chinese volunteers to evaluate its safety, tolerability pharmacokinetics and immunogenicity profiles of recombinant human interferon beta-1b (rIFN β-1b) by subcutaneous administration (SC).

The clinical study included four single-dose (SD) cohorts and one multiple-dose (MD) cohort. The single-dose part was designed as a double-blind, randomized, placebo-controlled, dose-escalation (4-16 MIU dose range) study. Eight participants enrolled in each single-dose cohort were allocated (3∶1) to receive either rIFN β-1b or placebo. The multiple-dose cohort was mainly designed to assess the pharmacokinetics and immunogenicity profile of rIFN β-1b, with 8 MIU dose for eight consecutive days in eight healthy volunteers. The blood concentration of rIFN β-1b and the titre of anti-drug antibody (ADA) were quantified by a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetic parameters were calculated using a non-atrioventricular model with the WinNonlin software. The safety monitoring was carried out across the trial.

All 40 healthy participants enrolled and completed the trial. In 4, 8, 12 MIU SD groups, the C_max were (63.18±34.64)、(125.17±59.19) and (214.00±89.02) pg·mL^-1, respectively; AUC_0-t were (3 247.63±1 842.60)、(7 903.33±3 427.03) and (9 740.00±2 333.47) h·pg·mL^-1, respectively; AUC_0-∞ were (4 374.00±1 087.74)、(8 861.67±3 677.13) and (10 528.33±2 344.60) h·pg·mL^-1, respectively. The mean C_max of rIFN β-1b approximately increased linearly with dose-relationship in the SD group (4-12 MIU) and the mean AUC_0-t and AUC_0-∞ showed the similar treand. The median t_max ranged from 5 to 12 hours in the SD groups. The median t_max was 4 hours in the MD group and no increase of the titre level of anti-drug antibody was found. The elimination half-life (t_1/2) was similar in all dose groups, approximately 50 hours. No serious adverse events occurred and all adverse events returned to normal or baseline level. The common adverse events were mainly influenza-like illness, injection site adverse reactions and fever, all of which were graded as mild (Grade 1) or moderate (Grade 2).

The rIFN β-1b showed safe and well-tolerated in single and multiple doses cohorts of this study. Systemic exposure of IFN β-1b increased with dose-relationship in the single-dose group. These findings support the necessity for further clinical studies.

To investigate the clinical efficacy of sevelamer combined with Shenshuaining and calcitriol in the treatment of stage 5 chronic kidney disease (CKD) patients complicated with chronic kidney disease-mineral and bone disorder (CKD-MBD).

Patients with stage 5 CKD and CKD-MBD were randomly assigned by a random number table method to the control group (n=54) and the treatment group (n=54). The control group received sevelamer (800 mg per dose, three times daily, taken with meals). On this basis, the treatment group additionally received Shenshuaining oral solution (10 mL per dose, three times daily) and calcitriol (0.25 μg, once daily, orally). The treatment lasted for 12 weeks. The two groups were compared in terms of clinical efficacy, renal function indicators [24-hour urinary total protein (24hUTP), serum creatinine (SCr), and blood urea nitrogen (BUN)], inflammatory cytokines [interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α)], biochemical indices [intact parathyroid hormone (iPTH)], bone metabolism indices [alkaline phosphatase (ALP) and 25-hydroxyvitamin D (25(OH)D)], and adverse reactions.

A total of 120 patients were screened, and 108 were enrolled (54 in each group). After treatment, the total effective rate was 96.30% (52 cases/54 cases) in the treatment group, higher than 81.48% (44 cases/54 cases) in the control group (P<0.05). After treatment, 24 h UTP, SCr, and BUN levels in the treatment and control groups were (0.83±0.25) vs. (1.32±0.41) g·L^-1; (130.28±29.74) vs. (174.91±34.18) μmol·L^-1; and (9.42±1.94) vs. (12.15±2.61) mmol·L^-1; respectively. IL-6, hs-CRP, and TNF-α levels were (14.32±3.07) vs. (17.61±3.58) ng·L^-1; (3.38±1.14) vs. (6.75±1.63) mg·L^-1; and (16.93±3.15) vs. (21.34±3.81) ng·L^-1, respectively. Serum phosphorus and PTH levels were significantly lower in the treatment group [(1.75±0.37) vs. (2.11±0.42) mmol·L^-1; (101.78±8.68) vs. (125.46±10.73) pg·mL^-1]; while ALP was reduced [(64.31±7.28) vs. (76.45±9.31) IU·L^-1] (all P<0.05). The incidence of adverse drug reactions was 11.11% (6 cases/54 cases) in the treatment group and 7.41% (4 cases/54 cases) in the control group, with no significant difference (P>0.05).

Sevelamer combined with Shen Shuai Ning and Calcitriol significantly improves renal function, bone metabolism, and inflammation in stage 5 CKD patients complicated with CKD-MBD compared to Sevelamer alone, with similar safety and better clinical efficacy.

With the release of guidance for adaptive design in clinical trials both domestically and internationally, designing interim analyses in clinical trials has great guiding significance for the success of clinical trials. It not only helps to improve research and development efficiency, but also has important preventive significance for clinical trials that have chosen incorrect statistical methods, resulting in serious issues such as type I error inflation and introduction of bias, which may lead to the failure of clinical trials. This article combines three cases that have occurred in current clinical trials to analyze and summarize the statistical issues related to confirmatory clinical trial interim analyses, promoting a deeper understanding of interim analyses and providing references for the high-quality design, implementation, analysis, and interpretation of results of confirmatory clinical trials..

This systematic review and Meta-analysis compared the efficacy and safety of dexibuprofen with ibuprofen across diverse clinical settings.

A comprehensive literature search was performed across multiple databases (PubMed, Embase, Web of Science, Scopus, Cochrane Library, and CNKI) to identify all relevant clinical trials comparing dexibuprofen and ibuprofen. Statistical analyses were conducted using RevMan 5.4.

A Meta-analysis incorporating 21 randomized controlled trials demonstrated that dexibuprofen showed no statistically significant differences in efficacy compared to ibuprofen at full-dose (RR=1.02, 95% CI: 0.99-1.05), 70% doses (RR=0.92, 95% CI: 0.72-1.17), or 50% doses (RR=0.99, 95% CI: 0.82-1.19). Subgroup analyses indicated comparable efficacy between dexibuprofen and ibuprofen for both adult analgesia (RR=1.09, 95% CI: 0.97-1.23) and pediatric antipyresis (RR=1.01, 95% CI: 0.98-1.04). Regarding safety, full-dose dexibuprofen showed a lower risk of adverse events compared to ibuprofen (RR=0.76, 95% CI: 0.58-1.00).

Dexibuprofen demonstrates comparable efficacy to ibuprofen, exhibits good dose-sparing characteristics in the fields of analgesia and antipyresis. Furthermore, it exhibits superior safety at equivalent doses, making it suitable for patient populations requiring reduced drug exposure or those at risk of gastrointestinal adverse reactions.

To investigate the clinical efficacy of betahistine mesylate combined with oxiracetam in the treatment of patients with posterior circulation ischemic vertigo (PCIV).

This prospective study included 80 patients with PCIV who were treated at our hospital between June 2022 and June 2024. The patients were randomly assigned into two groups: the observation group (40 cases, treated with betahistine combined with oxiracetam) and the control group (40 cases, treated with betahistine monotherapy). After two weeks of treatment, the following were assessed: vertigo symptom scores [Electronystagmography (ENG) score, Visual Vertigo Analogue Scale (VVAS), and Sheikh Control Scale (SCS)], imaging indicators, and serum-related factors.

After treatment, the nystagmogram score and Visual Vertigo Analog Scale (VVAS) score of the observation group were (3.08±0.86) and (37.13±3.26) points, respectively, which decreased significantly, while the Situational Vertigo Scale (SCS) score was (82.55±7.89) points, which increased significantly (P<0.05). The average blood flow velocities of the basilar artery and vertebral artery in the observation group were significantly higher than those in the control group (P<0.05). The serum levels of endothelin-1 (ET-1) and platelet-derived growth factor-BB (PDGF-BB) decreased, and the level of nerve growth factor (NGF) increased, with the observation group showing a better effect than the control group (P<0.05). The observation group experienced 2 cases of nausea and vomiting, 2 cases of rash, 2 cases of drowsiness, and 4 cases of dizziness, while the control group had 1 case of nausea and vomiting, 1 case of rash, and 1 case of dizziness, with no drowsiness reported. The incidence of adverse reactions was higher in the observation group than in the control group (χ²=4.501, P=0.034)(P<0.05).

Betahistine mesylate combined with oxiracetam significantly improves symptoms in patients with PCIV, enhances hemodynamics, and modulates serum factors, demonstrating promising clinical application potential.