Atients undergoing radical gastrectomy. METHODS: One hundred fifteen patients, ASA physical status I–III, who were scheduled for radical gastrectomy under general anesthesia, were enrolled in this study. Patient-controlled IV analgesia with fentanyl was administered during the first 48 hours after surgery. Visual analog scale score for patients’ pain was maintained at ≤30 mm. The amount of fentanyl consumed and side effects were recorded for the first 24 and 48 hours postoperatively. The SNPs of COMT (rs6269, rs4633, rs4818, and rs4680) of all patients were screened by DNA sequence analysis of polymerase chain reaction−amplified DNA or polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There were no significant differences in the doses of fentanyl used among patients possessing different SNPs of COMT rs6269, rs4633, rs4818, and rs4680 at 24 (all P > 0.207) and 48 (all P > 0.148) hours after surgery. COMT gene haplotypes combined by COMT rs6269, rs4633, rs4818, and rs4680, however, significantly affected fentanyl consumption at 24 (P = 0.029) and 48 (P = 0.032) hours after surgery. Among the haplotypes of COMT gene, patients with haplotype ACCG consumed more fentanyl than GCGG and ATCA haplotypes during the first 24 and 48 hours (all P < 0.042) after surgery. No significant differences were found in the incidence of nausea, vomiting, and dizziness among the 4 SNPs of COMT gene (all P > 0.079) and their haplotypes (all P > 0.482). CONCLUSIONS: COMT gene haplotype constructed by rs6269, rs4633, rs4818, and rs4680 contributes to the individual variation of postoperative analgesia with fentanyl. Patients carrying the COMT gene haplotype ACCG consumed the most drug during the first 24 and 48 hours postoperatively....

Background: Propofol is widely used for sedation of hysteroscopy. It can cause injection pain, respiratory depression, and hypotension. Remimazolam is a novel ultra-short-acting benzodiazepine. Clinical practice has found that the use of remimazolam alone often leads to body movement during hysteroscopy, which decreases the safety and comfort. Here this study is to investigate whether remimazolam combined with low-dose propofol can improve the sedation effect and safety of hysteroscopy. Patients and Methods: In this prospective, randomized, parallel-controlled trial, women (18 to 60 years) undergoing hysteroscopy were randomly assigned to receive propofol (Group P), remimazolam tosylate (Group R), or remimazolam tosylate plus propofol (Group RP). Intraoperative sedation depth was kept at the bispectral index (BIS) value of 40– 60. 6 μg/kg alfentanil was used for analgesic before sedation. Intraoperative low pulse oxygen saturation (SpO₂), body movement, injection pain, mean arterial pressure (MAP), heart rate (HR), and postoperative recovery time, dizziness, nausea and vomiting were recorded and compared. Results: From February to July 2022, 193 patients were recruited and randomly assigned to group P (n=64), group R (n=64), or group RP (n=65). There was no significant inter-group difference of the intraoperative BIS values. The incidence of low SpO₂, injection pain, hypotension, and postoperative dizziness in group RP were less than that in group P, and had no significant difference from group R. The incidence of body movement in group RP was less than that in group R, and had no significant difference from group P. Postoperative recovery time of group RP was shorter than that of the other two groups. No significant inter-group difference in bradycardia, nausea and vomiting was observed. Conclusion: Remimazolam tosylate combined with low dose of propofol improved sedation and safety in hysteroscopy, and may be a more ideal sedative method for hysteroscopy.

Defective mitophagy in renal tubular epithelial cells is one of the main drivers of renal fibrosis in diabetic kidney disease. Our gene sequencing data showed the expression of PINK1 and BNIP3, two key molecules of mitophagy, was decreased in renal tissues of VDR-knockout mice. Herein, streptozotocin (STZ) was used to induce renal interstitial fibrosis in mice. VDR deficiency exacerbated STZ-induced renal impairment and defective mitophagy. Paricalcitol (pari, a VDR agonist) and the tubular epithelial cell–specific overexpression of VDR restored the expression of PINK1 and BNIP3 in the renal cortex and attenuated STZ-induced kidney fibrosis and mitochondrial dysfunction. In HK-2 cells under high glucose conditions, an increased level of α-SMA, COL1, and FN and a decreased expression of PINK1 and BNIP3 with severe mitochondrial damage were observed, and these alterations could be largely reversed by pari treatment. ChIP-qPCR and luciferase reporter assays showed VDR could positively regulate the transcription ofPink1andBnip3genes. These findings reveal that VDR could restore mitophagy defects and attenuate STZ-induced fibrosis in diabetic mice through regulation of PINK1 and BNIP3.

Background: Chronic postsurgical pain (CPSP) is common and would reduce the quality of life of patients. Transversus abdominal plane (TAP) block has been widely used in lower abdominal surgery and many researches demonstrated that it could improve acute postsurgical pain. We aim to determine whether TAP block could improve chronic postoperative pain at 3 months and 6 months after colorectal surgery. Methods: A total of 307 patients received selective colorectal surgery under general anesthesia between January, 2015 and January, 2019 in a single university hospital were included: 128 patients received TAP block combined with patient-controlled intravenous analgesia (PCIA) for postsurgical analgesia (group TP) and 179 only administrated with PCIA (group P). Main outcome was the NRS score of pain at 3 months after colorectal surgery. The data was analyzed by two-way repeated measures anova and the chi-square test. Results: The NRS score at rest and during movement was decreased significantly at 24 h after surgery (rest NRS 1.07 ± 1.34 vs 1.65 ± 1.67, movement NRS 3.00 ± 1.45 vs 3.65 ± 1.89; all P = 0.003) in group TP than those of group P. There was no significant difference of NRS score at 48 h after surgery (P > 0.05). At 3 months after surgery, the NRS score during movement was also lower in group TP than that in group P (0.59 ± 1.23 vs 0.92 ± 1.65, P = 0.045). There was no significant difference of NRS score at 6 months after surgery (P > 0.05). The prevalence of CPSP was 19.5% (25/128) in group TP and 20.7% (37/179) in group P at 3 months after surgery. 13.2% (17/128) of patients suffered from CPSP in group TP and 13.9% (25/179) in group P at 6 months after surgery. Both at 3 months and 6 months after surgery, there was no statistical difference of the prevalence of CPSP between the two groups (all P > 0.05) . Conclusions: TAP block reduced NRS during movement at 3 months after surgery but did not reduce the incidence of CPSP at 3 months and 6 months after selective colorectal surgery.

The aim of this study was to investigate the effect of the µ-opioid receptor gene (OPRM1) A118G polymorphism on the requirement for post-operative fentanyl analgesia in patients undergoing radical gastrectomy. One hundred and twenty-eight gastric cancer patients scheduled to undergo radical gastrectomy under general anesthesia were enrolled in the study. Post-operative, patient-controlled intravenous analgesia of fentanyl was provided for satisfactory analgesia until 48 h after surgery. OPRM1 A118G was screened by DNA sequence analysis of polymerase chain reaction (PCR)-amplified DNA. Differences in fentanyl consumption and adverse effects were compared among the different genotypes at 24 and 48 h after surgery. The ranges of fentanyl dose in the 128 patients at 24 and 48 h after surgery were 5.4-17.3 µg/kg and 12.4‑29.9 µg/kg, respectively. Among these patients, there were 54 wild-type homozygotes (AA), 53 heterozygotes (AG) and 21 mutant homozygotes (GG). The frequency of the G allele was 0.371 in the OPRM1 polymorphism. There were no significant differences in fentanyl dose or adverse effects, including nausea, vomiting and dizziness, for the OPRM1 A118G polymorphism (P>0.05). The OPRM1 A118G polymorphism does not play a significant role in post-operative fentanyl analgesic dose or post-operative nausea, vomiting and dizziness in patients undergoing radical gastrectomy.

Background: Flurbiprofen axetil (FA) is a commonly prescribed agent to relieve perioperative pain, but the relationship between FA and postoperative acute kidney injury (AKI) remains unclear. This study attempted to evaluate the effects of different dose of perioperative FA on postoperative AKI.Methods: A total of 9915 patients were enrolled for this retrospective study. The clinical characteristics and the prevalence of postoperative AKI among patients non-using, using low dose (50-100 mg), middle dose (100-250 mg) and large dose (≧250 mg) of FA were analyzed respectively. The impact of different dose of FA on postoperative AKI was analyzed using univariable and multivariate logistic regression analysis.Results: The prevalence of postoperative AKI was 6.7% in the overall subjects and 5.1% in 2446 cases who used FA. The incidence of AKI in low dose group was significantly less than that of non use group (4.5% vs 7.2%,P < 0.001), but the incidence of AKI in large dose group was significantly higher than that in the non-use group (18.8% vs 7.2%,P < 0.001). However, there was no significant difference between patients without using FA and subjects using middle dose of FA (7.2% vs 5.6%,p = 0.355). Multivariate logistic regression analysis showed that low dose of FA was a protective factor for postoperative AKI (OR = 0.75,p = 0.0188), and large dose of FA was a risk factor for postoperative AKI (OR = 4.8,p < 0.0001).Conclusions: The impact of FA on postoperative AKI was dose-dependent, using of low dose FA (50-100 mg) perioperatively may effectively reduce the incidence of postoperative AKI.