This study aimed to evaluate analyze the current quality status of investigator-initiated trials (IITs) conducted in a hospital, analyze key influencing factors, explore targeted improvement measures, and provide references for enhancing the design level of IITs.

IITs registered in the Medical Research Registration and Filing Information System by the hospital from January 2020 to April 2025 were selected as the research objects. The research compliance, scientificity, and value were assessed, and then followed by statistical analysis.

Among the 124 IITs, 76% were initiated by investigators with associate senior titles or above. The median scores of the standardization and scientificity dimensions were both 8 points, while the median score of the research value dimension was 6 points. The total scores of interventional studies and observational studies were 23 and 21, respectively (P<0.01), and the total scores of multi-center studies and single-center studies were 23 and 20, respectively (P<0.001). Except for the correlation between funding support and the scientificity score, which the difference was not statistially signifccant (P>0.05), funding support showed a significant positive correlation with both the research compliance and research value dimensions (correlation coefficients ranging from 0.300 to 0.346, all P<0.001); disciplinary strength, and investigator title were significantly positively correlated with all three dimensions of research quality (correlation coefficients ranging from 0.213 to 0.380, P<0.01, P<0.001) and disciplinary strength had the greatest impact on research value.

Medical institutions still need to strengthen the standardization and scientificity of IITs, and there is great room for improvement in research value. Disciplinary strength, investigator background, and funding support are key factors affecting the research quality. From the perspective of institutional management, the quality of IITs can be effectively improved by constructing a systematical management system that integrates scientific review, methodological support and resource guarantee.

To investigate the efficacy and safety of programmed death-1 (PD-1) inhibitor targeted therapy combined with the oxaliplatin+5-fluorouracil+calcium leucovorin (mFOLFOX6) chemotherapy regimen in the preoperative neoadjuvant treatment of locally advanced middle-low rectal cancer.

Elderly patients with locally advanced middle-low rectal cancer were divided into control group and treatment group according to the treatment method. Patients in the control group received the conventional mFOLFOX6 chemotherapy regimen, with one cycle every 2 weeks for a total of 4 cycles. Patients in the treatment group received the conventional neoadjuvant chemotherapy with the mFOLFOX6 regimen combined with the PD-1 inhibitor camrelizumab injection (200 mg intravenously infused on day 1 of each cycle), with one cycle every 2 weeks for a total of 4 cycles. The surgical intervention was undertaken 4-6 weeks following completion of the chemotherapy regimen. The short-term efficacy evaluation of solid tumors, malignant tumor markers, anorectal dynamics and surgical efficiency were compared between the two groups and the safety was evaluction.

A total of 97 patients were recruited, with 54 assigned to the control group and 43 in the treatment group. After treatment, the objective response rates (ORR) were 25.93% (14 cases/54 cases) in the control group and 48.84% (21 cases/43 cases) in the treatment group; the disease control rates (DCR) were 57.41% (31 cases/54 cases) in the control group and 76.74% (33 cases/43 cases) in the treatment group, with statistically significant differences (P<0.05). After treatment, the carcinoembryonic antigen (CEA) levels in the control group and treatment group were (3.27±0.48) and (2.75±0.43) μg·L^-1, respectively; the carbohydrate antigen 199 (CA199) levels were (22.19±3.17) and (19.80±2.94) KU·L^-1, respectively. The above indicators demonstrated statistically significant differences between the treatment and control groups (all P<0.001). After treatment, the rectal resting pressure (RRP) levels in the control group and treatment group were (11.36±1.75) and (13.95±2.03) mmHg, respectively; the maximal tolerable rectalvolume (MTV) levels were (142.97±18.39) and (135.43±15.96) mL, respectively; the rectal compliance (RC) levels were (3.13±0.58) and (2.75±0.39) mL·mmHg^-1, respectively. The above indicators demonstrated statistically significant differences between the treatment and control groups (all P<0.05). The incidence of postoperative complications was 20.37% (11 cases/54 cases) in the control group and 18.60% (8 cases/43 cases) in the treatment group, with no statistically significant difference (P>0.05).

Preoperative targeted therapy with a PD-1 inhibitor combined with the mFOLFOX6 chemotherapy regimen can significantly improve the short-term efficacy of solid tumors, reduce tumor marker levels, optimize anorectal dynamics and quality of life in patients with locally advanced middle-low rectal cancer, with mild immunosuppression and good safety.

To explore the efficacy and safty of different administration routes of dexmedetomidine injection in elderly patients undergoing total hip arthroplasty (THA).

The elderly THA patients were randomly divided into the intravenous group (ID group, ropivacaine injection nerve block, 0.5 μg·kg^-1 dexmedetomidine injection administered by intravenous pump) and the perineural group (PD group, 0.5 μg·kg^-1 dexmedetomidine injection combined with ropivacaine injection nerve block). Compare the postoperative visual analog scale (VAS) scores, inflammatory factors, hemodynamic parameters, awakening time, incidence and duration of emergence agitation (EA), mini-mental state examination (MMSE) scores, riker sedation-agitation scale (RSAS), oxidative stress and immune function between the two groups and safty evaluation was conduated.

A total of 102 cases were included, 51 in the ID group and 51 in the PD group. At 48 hours after surgery, the resting VAS scores of ID group and PD group were (1.85±0.73) and (1.52±0.61) points, and the movement VAS scores were (3.61±0.64) and (3.27±0.42) points, respectively. The rest/movement VAS scores of PD group were significantly lower than those of ID group (all P<0.05). Immediately after surgery, C-reactive protein (CRP) in ID group and PD group were (6.80±1.03) and (6.13±0.75) mg·L^-1, interleukin-1β (IL-1β) were (8.06±0.87) and (6.07±0.63) pg·mL^-1, tumor necrosis factor-α (TNF-α) were (99.24±12.03) and (81.10±9.25) ng·mL^-1, interleukin-8 (IL-8) were (8.03±0.73) and (6.19±0.68) pg·mL^-1, interleukin-6 (IL-6) were (39.68±7.25) and (32.35±6.86) pg·mL^-1; 1 day after surgery, CRP in ID group and PD group were (6.07±1.07) and (5.37±0.81) mg·L^-1, IL-1β were (6.71±0.66) and (5.24±0.65) pg·mL^-1, TNF-α were (98.21±11.00) and (77.48±10.78) ng·mL^-1, IL-8 were (6.76±0.57) and (5.29±0.60) pg·mL^-1, IL-6 were (37.93±8.65) and (30.34±7.20) pg·mL^-1; 3 day after surgery, CRP in ID group and PD group were (5.53±1.04) and (5.06±0.64) mg·L^-1, IL-1β were (6.11±0.73) and (4.30±0.68) pg·mL^-1, TNF-α were (83.97±13.78) and (51.32±9.69) ng·mL^-1, IL-8 were (6.26±0.67) and (4.33±0.52) pg·mL^-1, IL-6 were (31.35±7.06) and (28.24±5.23) pg·mL^-1. The levels of CRP, IL-1β, TNF-α, IL-8 and IL-6 in PD group were statistically significantly lower than those in ID group immediately after operation, 1 day and 3 days after operation (all P<0.05). The recovery time of ID group and PD group was (28.93±3.00) and (25.93±2.91) min, respectively; the incidence of EA was 23.53% and 7.84%, respectively; the duration of EA was (2.32±0.38) and (1.82±0.36) days, respectively. Immediately after surgery, superoxide dismu-tase (SOD) in ID group and PD group were (136.47±16.96) and (154.81±15.38) U·mL^-1, malondialdehyde (MDA) were (8.89±1.24) and (6.54±1.13) nmol·mL ^-1, CD4⁺ were (29.28±2.94)% and (32.62±2.57)%, CD4⁺/CD8⁺ were (1.34±0.39)% and (1.55±0.37)%; 1 day after surgery, SOD in ID group and PD group were (149.82±17.54) and (157.73±16.52) U·mL^-1, MDA were (6.04±1.10) and (4.37±1.02) nmol·mL ^-1, CD4⁺ were (24.75±1.71)% and (28.36±2.31)%, CD4⁺/CD8⁺ were (1.24±0.31)% and (1.37±0.33)%; 3 day after surgery, SOD in ID group and PD group were (156.44±19.73) and (164.39±19.15) U·mL^-1, MDA were (5.27±0.95) and (4.05±0.68) nmol·mL ^-1, CD4⁺ were (27.35±1.78)% and (31.16±2.33)%, CD4⁺/CD8⁺ were (1.22±0.35)% and (1.43±0.40)%. SOD、CD4⁺、CD4⁺/CD8⁺ in PD group were statistically significantly higher than those in ID group (all P<0.05), MDA was statistically significantly lower than that in ID group (P<0.05). Among the routes of administration, ID was a risk factor for EA during general anesthesia in THA in elderly patients (P<0.05). Among the administration doses, different administration doses did not increase the risk of EA during general anesthesia in elderly patients with THA (P>0.05).

Compared with intravenous administration, peripheral dexmedetomidine injection can effectively reduce the incidence of EA, reduce inflammation and oxidative stress, improve analgesia and immune function in elderly patients with THA, and the effect can be achieved at a lower dose, which is recommended as the preferred anesthesia auxiliary scheme.

To analyze the role mechanism of xuesaitong injection (lyophilized) in the treatment of cerebral infarction by network pharmacology and molecular docking technology.

The intersection targets of five important active ingredients (Ginsenoside Rg1, Ginsenoside Rb1, Ginsenoside Re, Notoginsenoside R1, Ginsenoside Rd) in xuesaitong injection (lyophilized) and acute cerebral infarction were screened by database, and the target action network was constructed. Gene ontology (GO) pathway analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed by using digital-audio-video internet devince (DAVID) database, and molecular docking verification was performed.

A total of 61 non-redundant targets were screened for Panax notoginseng saponins, and 5 737 non-redundant targets were identified for cerebral infarction. The intersection of three databases yielded 64 common targets. After intersecting the drug targets with the disease targets, two overlapping targets were obtained: protein kinase C beta (PRKCB) and tumor necrosis factor (TNF). Intersection with the non-redundant disease targets yielded 51 overlapping targets. Based on network topology parameters and the intersection target results, caspase-3 (CASP3), TNF, nuclear factor kappa B subunit 1 (NFKB1), matrix metalloproteinase-9 (MMP9), tumor protein p53 (TP53), and PRKCB were selected for subsequent molecular docking. The results of GO functional enrichment analysis showed that in terms of biological processes, the target genes were mainly involved in the positive regulation of gene expression, the negative regulation of apoptosis process, and the positive regulation of miRNA transcription. In terms of cell components, the target genes were mainly located in extracellular space, extracellular region, blood, axon and protein complex. In terms of molecular function, the target proteins mainly had the same protein binding, protease binding, Heat shock protein 90 (HSP90) protein binding and other functions, and the enrichment results were statistically significant (all P<0.05). The results of KEGG enrichment analysis revealed that the potential targets of xuesaitong injection (lyophilized) in the treatment of cerebral infarction were enriched in advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway, lipid and atherosclerosis, fluid shear stress and atherosclerosis, proteoglycans in cancer, MAPK signaling pathway, thyroid hormone signaling pathway, apoptosis pathway and other signaling pathways, and the enrichment results were statistically significant (P<0.05). The results of molecular docking displayed that the main active ingredients of xuesaitong injection (lyophilized) had good binding ability with the core target protein, among which Ginsenoside Rg1 had the lowest binding energy with TNF, and CASP3, PRKCB showed strong binding with various active ingredients.

Xuesaitong injection (lyophilized) may play a multi-target comprehensive role in the treatment of cerebral infarction by regulating CASP3, TNF, NFKB1, MMP9, TP53, PRKCB and other key targets, acting on pathways such as apoptosis, inflammation and atherosclerosis.

To investigate the effects of roxadustat capsules combined with multi-dimensional exercise rehabilitation training on microinflammation and vascular endothelial function in elderly hemodialysis patients.

Elderly patients who underwent regular dialysis and took roxadustat capsules were randomly divided into the treatment group and the control group according to the random number table. Patients in the control group took roxadustat capsules. Patients in the treatment group were given roxadustat capsules combined with multi-dimensional exercise rehabilitation training. For those weighing less than 60 kg, treated with roxadustat capsules 100 mg per time; for those weighing more than 60 kg, took roxadustat capsules 120 mg each time; three times a week. The multidimensional exercise included resistance exercise, aerobic exercise, and mindfulness meditation during dialysis, 3 times per week, 70 minutes each session, lasting 6 months. Clinical efficacy, microinflammatory factor indicators, endothelial function indicators, biochemical indicators, and adverse drug reactions were collected before and after the study.

A total of 235 cases were enrolled in this study. The treatment group included 115 cases. The control group included 120 cases. After the treatment, the total effective rates of the treatment group and the control group were 90.43% (104 cases /115 cases) and 79.17% (95 cases /120 cases), respectively, and the difference was statistically significant (P<0.05). The total effective rate in the non-diabetic patients of the treatment group was 94.38% (84 cases /89 cases), significantly higher than the 80.65% (75 cases / 93 cases) in the diabetic patients of the treatment group (P<0.05). After treatment, the levels of serum nuclear transcription factor (NF-κB) in the treatment and the control groups were (24.78±4.67) and (36.09±4.25) ng·L^-1, respectively; interleukin-6 (IL-6) levels were (25.38±4.24) and (28.47±4.62) ng·L^-1; interferon-γ (IFN-γ) levels were (40.66±4.89) and (50.01±5.95) ng·L^-1; serum endothelin-1 (ET-1) levels were (87.41±26.59) and (120.70±28.52) ng·L^-1; soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were (2 848.50±84.75) and (5 639.82±125.63) μg·L^-1; and plasma endothelial microparticles (EMP) counts were (95.43±20.19) and (110.55±26.78) per μL, respectively. The above indicators in the treatment group were statistically significantly different from those in the control group (all P<0.05). The main adverse drug reactions in the treatment group and the control group were nausea, vomiting, indigestion and fatigue. The total incidence of adverse drug reaction rates in the treatment group and the control group were 11.30% (13 cases /115 cases) and 11.67% (14 cases /120 cases), respectively. There was no statistically significant difference (P>0.05).

Roxadustat capsules combined with multidimensional exercise rehabilitation training has shown significant efficacy in microinflammation and vascular endothelial dysfunction in elderly hemodialysis patients, which can reduce microinflammatory responses and improve vascular endothelial function, outperforming the effects of roxadustat capsules alone, with good safety.

To systematically elucidate the mechanism of action of Qizhi hypoglycemic tablets (QZT) in treating diabetic vascular complications, this study adopted the methods of network pharmacology and molecular docking.

Active ingredients and their corresponding targets of QZT were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and other databases. Disease targets related to diabetic nephropathy, retinopathy, and peripheral neuropathy were collected from The human gene database (GeneCards) and online mendelian inheritance in man (OMIM). Overlapping targets between drugs and diseases were identified, and a protein-protein interaction (PPI) network was constructed. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed using the database for annotation, visualization, and integrated discovery (DAVID). Molecular docking was used to validate the binding interactions between key active components and core targets.

A total of 116 active ingredients, 2 245 disease-related targets, and 354 common targets were obtained. Core targets such as proto-oncogene tyrosine-protein kinase (SRC), signal transducer and activator of transcription 3 (STAT3), estrogen receptor 1 (ESR1), and RAC-alpha serine/threonine-protein kinase (AKT1) were identified. GO and KEGG analyses revealed that the therapeutic effects of QZT were primarily mediated through key pathways including phosphatidylinositol 3-kinase/Akt signaling pathway (PI3K-Akt) and advanced glycation end products-receptor for advanced glycation end products signaling pathway (AGE-RAGE). Molecular docking confirmed stable binding of core components including apigenin, baicalein, and 4′,7-dihydroxyflavanone (DFV) to the core targets.

This study preliminarily clarifies the multi-component, multi-target, and multi-pathway mechanism of QZT against diabetic vascular complications, providing a theoretical basis for its clinical application and further investigation.

To develop a transdermal delivery system for tetraphydrocurcumin nanoemulsion-gel (Thc@NE@gel), and to investigate its therapeutic efficacy and mechanism of action in atopic dermatitis (AD).

Thc@NE@gel was prepared using a high-energy emulsification method combined with a low-temperature swelling process. The formulation was characterized for particle size, zeta potential, drug loading, encapsulation efficiency, morphology and physicochemical properties. In vitro transdermal absorption experiments were conducted using a Franz diffusion cell. An AD mouse model was established, and successfully induced mice were randomly divided into animal control group, positive drug group (10mg·kg^-1 dexamethasone gel), animal model group, Thc@NE group (Thc@NE 20 mg·kg^-1) and animal Thc@NE@gel low-, medium- and high-dose experimental groups (10, 20, and 30 mg·kg^-1 Thc@NE@gel), with 6 mice in each group. Body weights of mice in each group were measured and changes recorded; hematoxylin and eosin (HE) staining was performed to observe histopathological damage in skin tissue; enzyme-linked immunosorbent assay (ELISA) was used to detect serum inflammatory cytokine levels. Concurrently, an in vitro inflammatory model was established using human immortalized keratinocytes (HaCaT). Cells were divided into cell control group, cell model group (LPS 1 μg·mL^-1), cell low- and high-dose Thc@NE@gel expreimental groups (10 and 30 μM Thc@NE@gel). Reactive oxygen species (ROS) were measured in each group using flow cytometry; serum inflammatory cytokine levels were detected by ELISA; Western blot analysis was performed to detect the expression of key proteins in the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway.

Thc@NE@gel was developed with a particle size of (195.30±5.20) nm, a zeta potential of (-24.51±1.45) mV, and a encapsulation efficiency of (72.70±0.67)%. The body weights of mice in the animal Thc@NE@gel low-, medium-, and high-dose treatment groups, the animal blank group, the animal model group, the Thc@NE group, and the positive control (dexamethasone) group on day 17 were (21.50±1.20), (22.30±1.15), (24.00±1.25), (26.20±1.30), (17.30±1.10), (18.20±1.15) and (17.50±1.05) g, respectively; immunoglobulin E(IgE) levels were (40.52±10.23), (32.84±9.65), (30.67±10.12), (21.23±3.45), (53.21±4.12), (56.45±5.89) and (64.32±12.14) ng·mL^-1; IL-17 levels were (48.23±8.12), (25.43±4.67), (30.21±9.87), (23.45±5.12), (84.56±12.34), (54.12±5.67), and (47.89±6.78) pg·mL^-1; IL-23 levels were (45.67±3.12), (44.23±2.98), (40.12±2.45), (25.34±7.12), (73.45±15.67), (55.23±6.78), and (24.56±1.89) pg·mL^-1; when comparing the animal animal model group with the animal blank group, all of the above inflammatory markers showed statistically significant differences (all P<0.05). Compared with the animal model group, the IgE and IL-17 levels in the animal medium- and high-dose groups of Thc@NE@gel, as well as the IL-23 levels in all dose groups, showed statistically significant differences (all P<0.05); the IgE levels in the positive control group showed no statistically significant difference compared with the animal model group (P>0.05). Furthermore, the relative protein expression levels of cGAS in the low-dose and high-dose cell Thc@NE@gel experimental groups, the cell blank group, and the cell model group were 1.15±0.12, 0.82±0.08, 1.00±0, and 1.65±0.18, respectively; the relative protein expression levels of STING were 0.95±0.10, 0.60±0.06, 1.00±0.00, and 1.65±0.15, respectively. Compared with the animal blank group, all of the aforementioned indicators in the cell model group showed statistically significant differences (all P<0.001).

Thc@NE@gel enhances the anti-inflammatory effects of Thc, providing new insights for the development of skin delivery systems for natural active ingredients; furthermore, by inhibiting the cGAS-STING pathway, Thc@NE@gel improves atopic dermatitis, offering a new mechanistic perspective for its treatment.

To provide practical references for all participants in drug clinical trials on drug safety risk management and promote the construction of a more efficient clinical trial safety management system.

Based on the regulatory practice of 40 clinical trial safety risk control cases from the Center for Drug Evaluation in 2024, this paper uses classified statistics and correlation analysis methods to analyze the characteristics of safety risk information from multiple dimensions such as drug types and indications, and systematically sorts out the response logic of regulatory measures.

Among the 40 cases where risk management procedures were initiated, distinct risk characteristics were observed across different drug types and indications. The regulatory measures reflected the principle of matching the intensity of control with the risk characteristics.

Regulatory authorities have adopted differentiated regulatory requirements in accordance with the logic of risk classification and bottom-line thinking. The regulatory initiatives have gradually evolved into focusing on the optimization and full-chain improvement of sponsors’ risk management systems, providing crucial support for the protection of subjects’ rights and interests as well as the high-quality development of pharmaceutical innovation..