To observe the clinical efficacy and safety of continuous infusion of extremely low-dose dexmedetomidine hydrochloride injection combined with remifentanil hydrochloride for injection and propofol emulsion injection in elderly patients undergoing total hip arthroplasty (THA).

Elderly patients undergoing THA were divided into treatment group and control group according to the administration method. The control group was induced with intravenous injection of sufentanil citrate injection at a dose of 0.3 μg·kg^-1, propofol emulsion injection at a dose of 1.0-2.5 mg·kg^-1, and rocuronium bromide injection at a dose of 0.6-0.9 mg·kg^-1. Anesthesia was maintained with intravenous infusion of propofol emulsion injection at a dose of 4-6 mg·kg^-1·h^-1 and remifentanil hydrochloride for injection at a dose of 0.1-0.2 μg·kg^-1·h^-1. The treatment group received dexmedetomidine hydrochloride injection 0.2-0.5 μg·kg^-1 before anesthesia induction, followed by ultra-low dose dexmedetomidine hydrochloride injection 0.1-0.2 μg·kg¹·h^-1 intravenous infusion from after anesthesia induction to 30 min before the end of the operation, with other treatments the same as the control group. The vital signs of the two groups were compared after entering the room (T₀), immediately after tracheal intubation (T₁), at the time of upper tourniquet (T₂), when necrotizing bone and tissue were removed (T₃), when prosthesis was implanted (T₄), when tourniquet was released (T₅) and immediately after extubation (T₆) and the modified alert sedation/score (MOAA/S) was improved; the dosage of anesthetics, the occurrence of postoperative delirium, preoperative and postoperative neuronal injury markers, and neurotransmitter markers were compared between the two groups, and safety was evaluated.

A total of 120 patients were enrolled, including 63 cases in the treatment group and 57 cases in the control group. At T₁, the heart rate (HR) of treatment group and control group were (79.68±7.34) and (76.79±8.40) times·min^-1, respectively; at T₂, they were (81.43±7.37) and (78.68±7.49) times·min^-1, respectively; at T₃, they were (83.83±7.53) and (80.35±7.14) times·min^-1, respectively; at T₄, they were (82.63±6.90) and (79.77±7.39) times·min^-1, respectively; at T₅, they were (81.27±7.31) and (78.16±7.51) times·min^-1, respectively; at T₆, they were (86.16±7.32) and (83.74±7.31) times·min^-1, respectively. The heart rate of treatment group at each time were all significantly higher than those of control group (all P<0.05). At T₁, the mean arterial pressure (MAP) of treatment group and control group were (80.29±9.89) and (75.32±9.73) times·min^-1, respectively; at T₂, they were (82.10±10.00) and (77.18±9.82) times·min^-1, respectively; at T₃, they were (83.16±9.95) and (79.46±10.06) times·min^-1, respectively; at T₄, they were (82.83±9.58) and (77.19±9.92) times·min^-1, respectively; at T₅, they were (81.30±9.59) and (76.09±9.82) times·min^-1, respectively; at T₆, they were (84.14±9.87) and (82.12±9.97) times·min^-1, respectively. The MAP of treatment group at each time were all significantly higher than those of control group (all P<0.05). At T₁, the MOAA/S of treatment group and control group were (2.05±0.28) and (2.23±0.46) score, respectively; at T₂, the scores were (1.92±0.33) and (2.09±0.51) score, respectively; at T₃, the scores were (1.95±0.42) and (2.09±0.34) score, respectively; at T₄, the scores were (1.92±0.33) and (2.11±0.36) score, respectively; at T₅, the scores were (1.92±0.33) and (2.07±0.37) score, respectively; at T₆, the scores were (3.30±0.73) and (3.77±0.80) score, respectively. The MOAA/S scores of treatment group at each time were all significantly lower than those of control group (all P<0.05). The intraoperative propofol dosage in treatment group and control group were (381.81±46.48) and (407.25±49.36) mg, respectively; the intraoperative remifentanil dosage were (14.43±1.82) and (15.14±2.00) μg, respectively; the incidence of postoperative delirium at 72 h were 15.87% and 33.33%, respectively; the postoperative 24 h central nervous system-specific protein (S100β) levels were (0.59±0.11) and (0.66±0.14) μg·mL^-1, respectively; the postoperative 24 h glial fibrillary acidic protein (GFAP) levels were (0.87±0.29) and (1.02±0.22) ng·mL^-1, respectively; the postoperative 8 h 5-hydroxytryptamine (5-HT) levels were (168.91±18.25) and (159.35±17.54) μg·L^-1, respectively, with statistically significant differences (all P<0.05). The total incidence of adverse drug reactions were 12.70% in treatment group and 22.81% in control group, respectively, with no statistically significant difference (P>0.05).

Continuous infusion of extremely low-dose dexmedetomidine hydrochloride injection combined with remifentanil hydrochloride for injection and propofol emulsion injection in elderly patients undergoing THA can effectively improve intraoperative vital signs and postoperative recovery quality, enhance analgesia and sedation, reduce the dosage of remifentanil hydrochloride for injection and propofol emulsion injection, reduce the incidence of postoperative delirium, regulate the levels of neuronal injury markers and neurotransmitter markers, and has good safety.

To explore the molecular mechanism of losartan in alleviating renal injury in sepsis.

In animal experiment, mice were randomly divided into the sham group, the model group (modeled by cecal ligation and perforation), losartan group (losartan treatment at 15 mg·kg^-1 after modeling) and antagonist group [treated with the G protein-coupled receptor 84 (GPR84) antagonist GLPG1205 at 30 mg·kg^-1 after modeling], each group contained 10 mice. Enzyme-linked immunosorbent assay (ELISA) experiments were used to detect serum renal injury indicators, and immunohistochemistry was used to detect the protein expressions of GPR84 and cluster of differentiation 86 (CD86) in renal tissues. The expression of cytokines in renal tissues was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). In cell experiment, THP-1 cells were randomly divided into control group, induce group (induced to M1-type macrophages), medicine group (inducing +10 μg·mL^-1 losartan) and medicine+6-OAU group (induction +10 μg·mL^-1 losartan +1 μmol·L^-1 GPR84 antagonist 6-OAU), the relative expression levels of GPR84 protein was detected by Western blot assay, the relative expression level of CD86 was detected by immunofluorescence assay, and the expression of cytokines in cells was detected by RT-qPCR.

In animal experiments, the levels of blood urea nitrogen (BUN) in mice of the sham group, model group, losartan group and antagonist group were (48.55±4.54), (111.28±5.83), (71.52±4.79) and (79.10±8.12) mmol·L^-1, respectively; serum creatinine (SCr) were (13.33±1.58),(64.12±6.91), (30.43±5.80) and (40.09±4.49) μmol·L^-1, respectively; the average optical density values of GPR84 were 0.05±0.01, 0.08±0.01, 0.05±0.01 and 0.05±0.01, respectively; the average optical density values of CD86 were 0.03±0, 0.08±0.01, 0.05±0.01, 0.06±0.01, respectively; the relative expression levels of GPR84 mRNA were 1.00±0.13, 2.70±0.23, 1.78±0.15 and 1.12±0.09, respectively; interleukin (IL)-1β mRNA were 1.00±0.14, 1.78±0.24, 1.41±0.13 and 1.50±0.19, respectively; tumor necrosis factor-alpha (TNF-α) mRNA were 1.00±0.10, 1.85±0.12, 1.39±0.10 and 1.56±0.12, respectively; the relative expression levels of inducible nitric oxide synthase (iNOS) mRNA were 1.00±0.14, 3.33±0.23, 1.93±0.16 and 2.30±0.24, respectively. Compared between the model group and the sham group; compared the losartan group or the contagonist group with the model group and compared between the losartan group with antagonist group, the differences of the above-mentioned indicators were statistically significant (P<0.05, P<0.01, P<0.001). In cell experiments, the relative expression levels of GPR84 protein in the control group, induce group, medicine group and medicine+6-OAU group were 0.58±0.06, 0.94±0.11, 0.63±0.07 and 1.45±0.09, respectively; the fluorescence intensities of CD86 were (1 072.36±105.92), (3 209.59±206.38), (1 903.95±172.73) and (2 471.43±273.18) a.u.; the relative expression levels of iNOS mRNA were 1.00±0.11, 3.06±0.23, 1.98±0.27 and 2.85±0.24, respectively, the above-mentioned indicators compared between the control group and the induce group, compared between the medicine group and the induce group, and compared between the medicine+6-OAU group and the medicine group, the differences were all statistically significant (all P<0.001).

Losartan can alleviate renal injury in sepsis, which is related to the inhibition of GPR84-mediated M1 polarization of macrophages.

To explore the expression of thrombospondin-1 (THBS1) in pan-cancer and its relevance to tumor microenvironment (TME).

The discrepancies in the expression and prognostic significance of THBS1 were examined in 33 different types of tumors using TCGA and GTEx data. The correlation between THBS1 and the TME index, various factors like immune cell infiltration, tumor mutagenesis burden (TMB) and microsatellite instability(MSI) was evaluated using computational methods. The potential mechanism was also dissected by constructing interaction networks of THBS1 with other genes by GEPIA; this was validated using multiplex immunohistochemistry(mIHC) in pancreatic cancer (PAAD) tissues.

Pan-cancer analysis revealed THBS1 mRNA was differentially expressed in 17 common cancer types (all P<0.05) and differential expression of the THBS1 protein was observed in 9 cancer types (all P<0.001). Survival analysis indicated that higher THBS1 expression was significantly associated with poorer patient prognosis in various malignant tumors (P<0.05). THBS1 expression was statistically significantly correlated with cancer-associated fibroblast (CAFs) infiltration across all cancer types (P<0.05), and positively associated with the expression of multiple immune checkpoint genes, including CD274(P<0.001)、HAVCR2(P<0.001)、PDCD1LG2(P<0.001)、LAG3(P<0.001)、PDCD1(P<0.001)、CTLA4(P<0.001) and TIGIT(P<0.001). These findings suggested that THBS1 may contribute to reduced responsiveness to immunotherapy by shaping an immunosuppressive tumor microenvironment. Co-expression and enrichment analyses demonstrated that the integrin genes strongly correlated with THBS1 in pancreatic adenocarcinoma (PAAD) were ITGAV (r=0.60, P<0.001)、ITGB3 (r=0.54, P<0.001) and ITGB1 (r=0.69, P<0.001). These findings were validated in pancreatic cancer tissues: immunofluorescence co-localization analysis demonstrated a strong positive correlation between THBS1 expression and integrin ITGAV (r=0.75, P<0.001).

This study identifies THBS1 as a crucial pan-cancer prognostic biomarker and a key regulator of the TME, providing a compelling rationale for its potential as a therapeutic target in oncology.

This study systematically evaluated its clinical efficacy and safety of ceftolozane/tazobactam for gram-negative bacterial (GNB) infections.

Clinical studies on ceftolozane/tazobactam for GNB infections were retrieved from PubMed, Embase, Cochrane Library, CNKI, VIP, and WanFang databases from inception to April 2025. Study quality was assessed using the Cochrane Risk of Bias tool and Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan 5.4.1.

Twenty-two studies involving 5 728 patients were included. Ceftolozane/tazobactam demonstrated superior clinical efficacy against Pseudomonas aeruginosa infections compared to control drugs (OR=1.61; 95% CI: 1.07-2.42; I²=60%; P=0.02) and significantly higher bacterial eradication rates (OR=1.27; 95% CI: 1.05-1.55; I²=11%; P=0.01). No significant differences were observed in adverse event rates (OR=0.90; 95% CI: 0.70-1.15; I²=55%; P=0.40), serious adverse event rates (OR=0.83; 95% CI: 0.53-1.29; I²=73%; P=0.40), or all-cause mortality (OR=0.92; 95% CI: 0.78-1.10; I²=0%; P=0.37).

For GNB infections, ceftolozane/tazobactam exhibits non-inferior clinical efficacy and safety to comparator drugs with higher bacterial eradication rates. It may represent a preferred alternative for Pseudomonas aeruginosa nfections.

To explore the molecular mechanism of berberine in improving insulin resistance and liver lipid metabolism in obesity mice.

Sixty clean-grade C57BL/6 mice were randomly divided into control group (normal diet), model group (high fat diet), experimental-L group (model+50.00 mg·kg^-1 berberine), experimental-H group (model+100.00 mg·kg^-1 berberine), inhibitor NC group (model +100.00 mg·kg^-1 berberine + tail vein injection mmu-inhibitor NC), miR-125a inhibitor group (model +100.00 mg·kg^-1 berberine + tail vein injection of mmu-miR-125a inhibitor). Berberine was administered by gavage once a day, and subcutaneous injection was performed every 4 days. After a continuous treatment period of 28 days, the insulin resistance levels were detected, serum lipid levels were analyzed, the expression levels of related genes were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the expression of related proteins in liver tissue was detected by Western blot (WB).

The levels homeostatis model assessment of insulin resistance (HOMA-IR) in control group, model group, experimental-H group, inhibitor NC group and miR-125a inhibitor group were 2.56±0.11, 7.23±0.67, 5.04±0.20, 4.99±0.34 and 6.46±0.40, respectively; triglyceride (TG) levels were (0.46±0.04), (0.93±0.08), (0.65±0.05), (0.63±0.06) and (0.74±0.06) mmol·L^-1, respectively; the relative expression levels of miR-125a were 1.00±0.12, 0.56±0.07, 0.77±0.10, 0.78±0.11 and 0.21±0.03, respectively; fatty acid synthase (FAS) mRNA were 1.00±0.10, 1.90±0.14, 1.40±0.22, 1.41±0.16 and 1.67±0.14, respectively; the relative protein expression levels of phosphorylated phosphatidylase 3-kinase (p-PI3K) were 0.78±0.09, 0.42±0.05, 0.69±0.06, 0.70±0.03 and 0.51±0.06, respectively; phosphorylated protein kinase B (p-AKT) protein levels were 0.84±0.12, 0.30±0.05, 0.64±0.08, 0.65±0.08 and 0.49±0.07, respectively. Compared between the model group and the control group; between the experimental-H group and the model group; and between the miR-125a inhibitor group and the inhibitor NC group, all differences of the above inclicatovs went statistically significant (P<0.01, P<001).

Berberine may improve insulin resistance and fat metabolism in obesity mice by activating PI3K/AKT signal through miR-125a.

To collect the case reports of hypersensitivity reactions induced by etoposide and systematically summarize the characteristics, clinical manifestations, and treatment outcomes of hypersensitivity reactions, in order to provide corresponding reference for the safe use of etoposide.

The related case reports of hypersensitivity reactions induced by etoposide were retrieved and collected from databases such as China National Knowledge Infrastructure China Hospital Knowledge Base, Wanfang, VIP, Pubmed and Web of Science, and basic information such as patient gender, age, medication use, time of hypersensitivity reaction occurrence, and treatment outcomes was statistically analyzed as well.

A total of 27 case reports were finally included, involving 34 patients which included 21 males and 12 females and 1 patient whose gender was not mentioned. The average age of the patients was (45.83±15.50) years, with approximately 60% being over 40 years old. The majority of included cases were lung cancer patients, and the occurrence time of hypersensitivity reactions induced by etoposide was relatively short, with 18 patients experiencing hypersensitivity reactions within 1-10 minutes of medication, while only 3 patients had hypersensitivity reactions that occurred for more than 1 hour. Hypersensitivity reactions could affect many systems of the body, such as respiratory, circulatory, skin and its appendages. Common clinical manifestations of hypersensitivity reactions included difficulty breathing, chest tightness, papules, palpitations, hypotension, cyanosis; in addition, there were many serious cases such as anaphylactic shock. All cases showed improvement after treatment, and the patient did not experience any hypersensitivity reactions after receiving another infusion of etoposide, which had been pre treated with hormones or anti allergic drugs.

Hypersensitivity reactions induced by etoposide belong to immediate hypersensitivity reactions, characterized by short onset time, rapid progression, and good prognosis. In clinical practice, it is necessary to closely observe the status of patients during infusion of etoposide, strengthen medication monitoring, which can ensure the safety use of etoposide.

To track and follow up serious adverse event (SAE) occurring at a tertiary hospital clinical trial institution in Hunan province, analyze and summarize the occurrence and outcomes of SAEs, and propose interventions and improvement measures to standardize the handling of SAE, report them promptly, protect the safety of research participants, ensure the reliability of clinical trial data, and improve the level of clinical trials.

A total of 528 SAEs related to cancer drugs were collected from this clinical trial institution from January 2020 to December 2024 and analyzed using SPSS 25.0 software.

The results showed that the main departments where SAEs occurred were oncology (35.25%), pulmonology (21.21%), and hematology (10.04%). SAEs were mainly concentrated in phase III clinical trials, accounting for 69.51% of the total SAE cases. The SAE predominantly affected the respiratory system, hematologic system, and gastrointestinal system, with grade 3 severity being most common (46.02%). The outcomes for research participants were generally favorable, 39.77% fully recovered and 25.00% improved.

Clinical trial institutions need to strengthen drug safety monitoring, promptly evaluate SAE, enhance supervision over SAEs, and safeguard the rights and safety of research participants.

To conduct a systematic analysis of the issues identified during routine quality control of clinical trials, investigate the root causes of quality problems in the trial implementation process, and explore improvement measures to enhance quality.

Issues identified in 255 routine quality control activities across 142 clinical trials from February 2023 to May 2025 were collected. These issues were categorized, aggregated, and subjected to statistical analysis.

A total of 248 issues were identified. These were primarily concentrated at the trial implementation level, specifically: 77 (31.05%) pertained to essential document management, 74 (29.84%) to the standardization of source records, 25 (10.08%) to the proper execution of informed consent forms, 23 (9.27%) to the completeness of source data, and 15 (6.05%) to the completeness of researcher credentials. Analysis of the causes indicated that these problems were mainly associated with ineffective researcher training, lack of active participation from investigators, deficiencies in the management and training of clinical research coordinators (CRCs), and insufficient quality control practices within specialty teams.

The institution exhibits a prominent proportion of issues related to essential document management and the standardization of source records. To reduce the occurrence of these problems and improve clinical trial quality, it is necessary to strengthen researcher training, enhance engagement, standardize CRC management, and improve the effectiveness of quality control within specialty teams.