To conduct a statistical analysis of clinical trial visit time windows and propose targeted recommendations based on risk management from the perspective of the institutional office, so as to provide references for clinical research practice.

Data of drug clinical trial projects undertaken by a single institution from 2018 to 2024 were collected. Visit time windows were statistically analyzed and compared across the screening phase, visit phase, and follow-up phase. A risk classification standard for time windows was established by integrating management practice, regulatory requirements, and relevant literature. Corresponding recommendations were put forward for sponsors, researchers, participants, and the institutional office based on this classification.

A total of 137 projects were included, with the number of visits ranging from 1 to unlimited. Visit modalities included on-site visits and remote visits (telephone visits). The most prevalent time windows in each phase were 28 days (45.99%) for the screening phase, 3 days (62.26%) for the visit phase, and 7 days (68.93%) for the follow-up phase. The risk classification results were as follows: extremely high-risk time windows (1 to 30 minutes in the visit phase), high-risk time windows (42 to 183 days: before screening in the screening phase, 1 to 24 hours in the visit phase, and 1 to 3 days in the follow-up phase), medium-risk time windows (1 to 7 days: before screening in the screening phase, 1 to 3 days in the visit phase, and 5 to 10 days in the follow-up phase), and low-risk time windows (14 to 35 days: before screening in the screening phase, 4 to 14 days in the visit phase, and 14 to 30 days in the follow-up phase). Compared phase Ⅱ with phase Ⅲ or phase Ⅳ, statistically significant differences were all observed in the distribution of visit windows during the visit phase (all P<0.05). Based on this classification, the institutional office recommends that all parties adopt strategies of scientific design, risk-based response, and closed-loop management, and deeply understand and actively cooperate with each other for different risk levels of time windows.

Significant differences exist in visit time windows across different phases of clinical trials. Risk classification and targeted responses from all parties can effectively ensure the quality of clinical trial data and the rights and interests of participants.

To clarify the role of acyl-CoA thioesterase 8 (ACOT8) across cancers, particularly its prognostic value, and its links to ferroptosis and the immune microenvironment in prostate cancer (PCa).

Using data from The Cancer Genome Atlas (TCGA), R software was used to analyze the gene differential expression of ACOT8 in pan-cancer and the correlation between prognosis. The single sample gene set enrichment analysis (ssGSEA), cell-type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) and tumor immune dysfunction and exclusion (TIDE) algorithms were employed to assess correlations with ferroptosis and immune cell infiltration.

ACOT8 was upregulated in 11 cancers and high expression predicted poor survival, most significantly in PCa. In PCa, ACOT8 expression was negatively correlated with ferroptosis activity and positively correlated with immunosuppressive cells.

ACOT8 is a poor prognostic marker in PCa, potentially by inhibiting ferroptosis and promoting an immunosuppressive microenvironment.

To evaluate the in vitro antibacterial effects and post-antibiotic effect (PAE) of dequalinium chloride against common pathogens isolated from oral infections in China in recent years.

The minimum inhibitory concentration (MIC) was determined by the standard microbroth or agar (for anaerobes) two-fold dilution method; the minimum bactericidal concentration (MBC) was determined by the broth two-fold dilution method; time-kill curves and PAE were determined by the colony count method.

MICs of dequalinium chloride and commonly used antimicrobial drugs were determined for 274 bacterial strains from 22 hospitals in 19 cities across China. Result showed that, for Gram-positive bacteria, the MIC₅₀ values of dequalinium chloride against Staphylococcus aureus and Streptococcus pyogenes were 1 and 2 mg·L^-1, respectively, with MIC₉₀ values of 2 and 4 mg·L^-1, respectively. For Streptococcus pneumoniae, Enterococcus faecalis, and the viridans group streptococci, the MIC₅₀ values were 8, 4 and 8 mg·L^-1, respectively, while the MIC₉₀ values were 8, and 16 mg·L^-1, respectively. Among Gram-negative bacteria, the MIC₅₀ and MIC₉₀ values of dequalinium chloride against Klebsiella pneumoniae were both 64 mg·L^-1; and >512 mg·L^-1 for MIC₅₀ against Pseudomonas aeruginosa. For 32 strains of anaerobic bacteria, the MIC₅₀ and MIC₉₀ of dequalinium chloride were 16 and 128 mg·L^-1, respectively. Dequalinium chloride showed superior antibacterial activity against genera of Peptostreptococcus and Porphyromonas compared to Prevotella. MBC and time-kill curves showed that dequalinium chloride has a good bactericidal effect on Staphylococcus aureus, Streptococcus pyogenes, and oral streptococci, killing bacteria from an initial count of 1.0×10⁵-1.0×10⁶ CFU·mL^-1 to 0 at 1-4 times MIC concentration within 4-24 h. It also showed good bactericidal effect on Enterococcus faecalis. The time-kill curves indicating a concentration-dependent characteristic of the drug. The PAE of dequalinium chloride against the above four bacterial strains was between 0.5-1 h.

Dequalinium chloride exhibits superior antibacterial activity against Gram-positive bacteria than Gram-negative bacteria and anaerobes, especially against Staphylococcus aureus and Streptococcus pyogenes, warranting further clinical research.

To understand the distribution and antibiotic resistance changes of clinical isolated Klebsiella pneumoniae in Xinjiang from 2019 to 2023, and provide a basis for the rational use of antibiotics in clinical practice.

Clinical isolates from Xinjiang region between 2019 and 2023 were collectd and identified and subjected to drug sensitivity tests using the fully automated bacterial identification analyzer VITEK-2 compact and VITEK-MS, supplemented by the K-B paper method.

Over the course of 5 years, a total of 72 678 strains of Klebsiella pneumoniae were detected, among which 19 061 were extended-spectrum β-lactamases (ESBLs) producing strains, accounting for a detection rate of 26.23%. The strains mainly come from sputum, urine, blood, etc. The top three departments in terms of strain distribution were the intensive care medicine, respiratory medicine, and pediatrics. The resistance rates of Klebsiella pneumoniae to third-generation cephalosporins ceftriaxone and ceftazidime were 21.42% and 15.73%, respectively. The resistance rates to carbapenems ranged from 6.82% to 7.48%, and the resistance rate to amikacin was 4.15%.

Klebsiella pneumoniae has become one of the most common pathogenic bacteria in clinical practice. The resistance of Klebsiella pneumoniae detected in Xinjiang is not optimistic. In order to improve the treatment effect of antibiotics, the resistance of antibiotics in the local area should be continuously monitored, and antibiotics should be selected reasonably based on drug sensitivity results.

To observe the clinical efficacy and safety of emedastine difumarate sustained-release capsules in conjunction with tacrolimus ointment for treating elderly patients with skin pruritus.

The senile patients with pruritus who were treated in our hospital were divided into control group and treatment group according to the treatment methods. The control group was treated with tacrolimus ointment twice a day on the basis of conventional treatment for 6 consecutive weeks. The treatment group, on the basis of the control group, orally administered 2 mg of emestine fumarate sustained-release capsules after breakfast or before going to bed, twice a day for 6 consecutive weeks. The clinical efficacy of patients, evaluation of itching degree, the levels of eosinophils (EOS), histamine and immunoglobulin E (IgE), levels of inflammatory response indicators recurrence situation, and safety were compared between two groups.

A total of 122 cases were included in this study, including 59 cases in the control group and 63 cases in the treatmnet group. The total effective rates of treatment in the treatmnet group and the control group were 92.06% (58 cases/63 cases) and 76.27% (45 cases/59 cases), respectively; the pruritus degree scores were (2.35±0.48) and (2.64±0.52) points, respectively; the EOS were (208.07±33.69) and (225.61±34.82) ×10⁶·L^-1 respectively; the histamine was (0.79±0.13) and (1.25±0.21) ng·mL^-1, respectively; the IgE was (42.07±6.56) and (45.17±6.08) ng·mL^-1, respectively; the monocyte chemoattractant protein-1 was (279.77±39.14) and (298.52±47.64) pg·mL^-1, respectively; the eosinophil chemoattractant was (44.77±6.21) and (47.96±7.45) pg·mL^-1, respectively; the interleukin-6 was (6.56±1.07) and (7.13±1.08) pg·mL^-1, respectively; the tumor necrosis factor -α was (5.91±0.69) and (6.24±0.89) pg·mL^-1, respectively, and the recurrence rates were 11.11% and 25.42%, respectively. The comparison of above indicators showed that there were statistically significant differences between the two groups (P<0.05, P<0.01, P<0.001). The adverse reactions in the control group included a burning sensation on the skin and rosacea, while those in the treatmnet group included a burning sensation on the skin, rosacea, drowsiness, headache, dizziness and tinnitus. The adverse reaction rates of the control group and the treatmnet group were 11.86% and 19.05%, without tatistically significant difference (P>0.05).

Emedastine difumarate sustained-release capsules combined with tacrolimus ointment can alleviate patients′ pruritus symptoms, reduce inflammatory response, regulate immune function, improve efficacy and reduce the risk of recurrence without increasing adverse reactions.

To observe the clinical efficacy and safety of trifluridine-tipiracil hydrochloride tablets combined with tislelizumab injection and fruquintinib capsules in advanced colorectal cancer patients after progression in second-line treatment.

Advanced colorectal cancer patients who had progression after second-line treatment were divided into the control group and the treatment group according to the treatment methods. The control group received tislelizumab injection 200 mg combined with fruquintinib capsules 5 mg, and the treatment group received 25 mg·m² trifluridine-tipiracil hydrochloride tablets combined with tislelizumab injection and fruquintinib capsules. A 21-day period was considered as one cycle, and both groups were treated continuously for 3 cycles. Clinical efficacy, tumor marker levels, angiogenesis factor levels, safety evaluation and survival were compared between the two groups.

This study enrolled 86 patients in total. The control group consisted of 45 patients, while the treatment group had 41 patients. After treatment, the disease control rates of the control group and the treatment group were 48.89% (22 cases/45 cases) and 73.17% (30 cases/41 cases), respectively; the levels of carbohydrate antigen 125 were (51.97±6.49) and (48.17±4.55) U·mL^-1, respectively; the levels of cytokeratin 19 fragment antigen 21-1 were (24.41±4.54) and (21.53±3.56) μg·L^-1, respectively; the levels of carcinoembryonic antigen were (30.84±6.42) and (27.76±4.44) ng·mL^-1, respectively; the levels of vascular endothelial growth factor (VEGF) were (97.82±16.74) and (90.29±16.74) pg·mL^-1, respectively; the levels of angiopoietin (Ang)-1 were (11 829.14±1 367.27) and (12 612.20±1 889.47) pg·mL^-1, respectively; the levels of Ang-2 were (486.90±113.66) and (430.59±76.93) pg·mL^-1, respectively; the levels of interleukin (IL)-8 were (10.54±2.39) and (9.05±1.85) pg·mL^-1, respectively; and the median progression free survival periods were 11 and 16 months, respectively. The above indicators of the treatment group were statistically significant different compared with the control group (all P<0.05). The main adverse drug reactions in the treatment group and the control group were nausea and vomiting, leukopenia, anemia, thrombocytopenia, hematochezia, elevated alanine aminotransferase, hand-foot syndrome, hypothyroidism, oral mucositis, hypertension and proteinuria. There was no statistically significant difference in the incidence of adverse drug reactions between the treatment group and the control group (P>0.05).

Trifluridine-tipiracil hydrochloride tablets combined with tislelizumab injection and fruquintinib capsules can significantly improve the clinical efficacy in patients with advanced colorectal cancer who progressed after second-line treatment, prolong progression-free survival, reduce angiogenesis factor levels, and have a certain degree of safety.

To investigate the effect of sestrin 2 (SESN2) on JS-1 cell activation through unc-51-like kinase 1 (ULK1) and its mechanism.

The JS-1 cells were divided into seven groups: the control group (cultured under normal conditions), si-NC group (transfected with si-NC), the si-SESN2 group (transfected with si-SESN2), model group (cultured in medium containing 5 μg·L^-1 transforming growth factor-β1 for 24 h), model + oe-SESN2 group (transfected with oe-SESN2 on the basis of the model group), model + si-SESN2 group (transfected with si-SESN2 on the basis of the model group), and model+si-SESN2 + oe-ULK1 group (co-transfected with si-SESN2 and oe-ULK1 on the basis of the model group). The levels of fibrous actin (F-actin) was detected by immunofluorescence. Quantitative real time polymerase chain reaction was used to detect the ULK1 mRNA level. The relevtive expression levels of SESN2, light chain 3 Ⅱ/Ⅰ (LC3Ⅱ/Ⅰ), connective tissue growth factor (CTGF), collagen type I α1 (Col1a1), phospho-c-Jun N-terminal kinase (p-JNK), c-Jun N-terminal kinase (JNK), c-Jun and activating transcription factor 2 (ATF2) were detected by Western Blot. Cell proliferation rate was detected by cell counting kit-8. Transwell assesses the ability of cells to invade.

The relative expression levels of SESN2 protein in the control group, model group, model+oe-SESN2 group, and model+si-SESN2 group were 1.00±0.19, 2.57±0.49, 3.61±0.68, and 1.66±0.31, respectively; the relative fluorescence intensity of F-actin was 1.00±0.18, 4.57±0.92, 6.33±1.19, and 2.81±0.57, respectively; the relative expression levels of ULK1 mRNA were 1.00±0.15, 2.67±0.48, 3.52±0.66, and 1.95±0.37, respectively. The relative expression levels of LC3Ⅱ/Ⅰ protein in the control group, model group, model+oe-SESN2 group, model+si-SESN2 group, and model+si-SESN2+oe-ULK1 group were 1.00±0.20, 2.79±0.53, 3.57±0.68, 1.88±0.35, and 2.51±0.48, respectively; the cell proliferation rates were (100.00±2.23)%, (141.31±4.17)%, (156.52±8.84)%, (109.49±7.35)%, and (127.08±8.16)%, respectively; the number of cell invasions was 66.04±11.45, 137.84±21.73, 215.19±35.28, 75.46±13.51, and 124.27±19.50, respectively; the relative expression levels of CTGF protein were 1.00±0.17, 2.65±0.51, 3.77±0.72, 1.51±0.29, and 2.53±0.51, respectively; the relative expression levels of Col1a1 protein were 1.00±0.15, 2.93±0.57, 3.88±0.75, 1.61±0.31, and 2.72±0.52, respectively; the relative phosphorylation levels of JNK protein were 1.00±0.16, 2.21±0.42, 3.08±0.59, 1.46±0.29, and 2.04±0.37, respectively. Compared with the control group, the above indicators of the model group showed statistically significant differences; compared with the model group, the above indicators of the model+oe-SESN2 group or model+si-SESN2 group showed statistically significant differences; compared with the model+si-SESN2 group, the above indicators of the model+si-SESN2+oe-ULK1 group all showed statistically significant differences (P<0.05, P<0.01, P<0.001).

SESN2 activates ULK1, promotes JS-1 cell activation, promotes cell proliferation and invasion, and regulates cell homeostasis, possibly through the activation of JNK signaling pathway.

To observe the clinical efficacy and safety of quilu tablets combined with lithium carbonate tablets and modified electroconvulsive therapy (MECT) in the treatment of bipolar disorder.

Patients with bipolar disorder were divided into control group and treatment group, both receiving routine treatment. The control group received MECT in addition to conventional treatment, with 3 sessions per week, administered every other day, totaling 12 treatments. During the treatment period, the patient was prescribed sustained-release lithium carbonate tablets with an initial dose of 0.25 g·d^-1, administered in 1-2 divided doses. Serum lithium levels were monitored weekly, maintained within the therapeutic range of 0.8-1.2 mmol·L^-1, and the medication was continued for a total of 6 weeks. The treatment group took quetiapine fumarate tablets orally after meals based on control group. The total doses for the first 4 days were 50, 100, 20 and 300 mg, respectively, taken in 2 doses. After the 4th day, the dose gradually increased to 300-450 mg·d^-1, and the dose was adjusted according to the patient’s clinical response and tolerance. The intake was controlled at 150-750 mg·d^-1, and the medication was shared for 6 weeks. Clinical efficacy, serological testing, depression and mania severity, cognitive ability, social function and occurrence of adverse drug reactions were compared between the two groups.

A total of 136 cases were screened in this study. Among them, 22 did not meet the inclusion and exclusion criteria, leaving 114 eligible for the study. They were divided into treatment group and control group, each comprising 57 cases. Six cases in control group were excluded due to personal reasons and loss to follow-up, while two cases in treatment group were excluded due to adverse drug reactions and loss to follow-up. Ultimately, 51 and 55 cases were included in control and treatment groups, respectively. After 6 weeks of treatment, the overall response rates were 72.55% (37 cases/51 cases) and 89.09% (49 cases /55 cases) in control and treatment groups; thyroid-stimulating hormone (TSH) levels were (2.72±0.42) and (2.90±0.44) μIU·mL^-1, respectively; prolactin (PR) levels were (13.58±2.40) and (15.27±2.56) ng·mL^-1, respectively; Hamilton depression scale -17 (HAMD-17) scores were (9.53±1.79) and (8.76±1.67) score, respectively; Bech - Rafaelsen mania rating scale (BRMS) scores were (7.04±1.39) and (6.47±1.35) score, respectively; Hopkins verbal learning test-revised (HVLT-R) scores were (26.94±4.85) and (29.76±3.81) score, respectively; continuous performance test (CPT) scores were (0.79±0.12) and (0.84±0.10) score, respectively; and social dysfunction screening scale (SDSS) scores were (6.92±1.18) and (6.38±0.99) score, respectively. All these indicators in treatment group showed statistically significant differences compared to control group (all P<0.05). During treatment, the main adverse drug reactions in treatment group were drowsiness, dry mouth, dizziness and orthostatic hypotension; while those in control group were nausea, drowsiness, dry mouth and constipation. The overall incidence of adverse drug reactions were 11.76% (6 cases/51 cases) and 7.27% (4 cases /55 cases) in control and treatment groups, respectively, with no statistically significant difference (P>0.05).

Quetiapine tablets combined with lithium carbonate tablets and MECT are more effective than using only lithium carbonate tablets and MECT in treating bipolar disorder, and the safety is good.