Combining cisplatin with Pinellia pedatisecta Schott lipid-soluble extract induces tumor immunogenic cell death in cervical cancer.

BACKGROUND: Pinellia pedatisecta Schott extract (PE) is extracted from Pinellia pedatisecta Schott (PPS), a traditional Chinese medicinal plant with the potential for direct anticancer effects or eliciting an anti-tumor response by activating the immune system. PURPOSE: To explore PE's ability and mechanism to reconstruct cisplatin's immunogenicity. METHODS: Cervical cancer cells were treated with cisplatin (CDDP) and/or PE. The exposure of calreticulin (CRT) on cell membrane was investigated by flow cytometry. The extracellular of ATP and HMGB1 was investigated by Western blot analysis, immunofluorescence and ELISA assay. Changes in immune profiles were using flow cytometry in vaccination and anti-tumor assays in vivo. Lastly, the mechanism of PE influenced the ROS/ERS pathway was examined by ROS assay kit, flow cytometry and Western blotting. RESULTS: PE treatment induced translocation of CRT from the endoplasmic reticulum to the cell membrane of tumor cells, concomitantly triggering immunogenic cell death (ICD). In terms of mechanisms, endoplasmic reticulum (ER) stress relievers could impede the ability of PE to induce immunogenicity. This indicates that PE is activated by ER stress, leading to subsequent induction of ICD. Upon analyzing RNA-seq data, it was observed that PE primarily induces programmed cell death in tumors by impeding upstream antioxidant mechanisms. Additionally, it transforms dying tumor cells into vaccines, activating a series of immune responses. CONCLUSIONS: This study observed for the first time that PE-induced CRT exposure on the membrane of cervical cancer cells compensates for the defect of nonimmunogenic cell death inducer CDDP thereby stimulating potent ICD. This ability restores the immunogenicity of CDDP through ER stress induced by the ROS signal. ROS played a role in PE's ability to induce ICD, leading to increased expression of ER stress-related proteins, including ATF3 and IRE-1α. PE exerted anti-cancer effects by increasing the ROS levels, and ROS/ERS signaling may be a potential avenue for cervical cancer treatment. Hence, the synergistic use of PE and CDDP holds potential for enhancing immunochemotherapy in cancer treatment.

Combined ultrasound and low temperature pretreatment improve the content of anthocyanins, phenols and volatile substance of Merlot red wine.

Ultrasound combined with low temperature treatment is a new food processing technology. In this study, low temperature, three ultrasound power levels, and their combinations were adopted in the must before fermentation to study their effects on Merlot red wine. The results showed that ultrasound combined with low temperature pretreatment increased the total and monomer contents of anthocyanins and phenols, affected the color of the wine, and significantly increased its antioxidant capacity. In particular, 240 W of ultrasound combined with low temperature pretreatment reduced the bad odors (caprylic acid, benzaldehyde, and 1-ethanol content) and improved the flower and fruit aroma (1-octanol and phenethyl acetate), as well as the aftertaste, thus improving the quality of the wine. Ultrasound combined with low temperature pretreatment positively affected the quality of Merlot red wine.

Effect of opioid-free anesthesia on postoperative analgesia after laparoscopic gynecologic surgery.

BACKGROUND: We performed this randomized controlled trial to evaluate the effect of opioid-free anesthesia (OFA) on postoperative analgesia after laparoscopic gynecologic surgery. METHODS: Seventy-eight patients undergoing laparoscopic gynecologic surgery were randomized to receive either OFA (group OF) or opioid-inclusive anesthesia (group C). Postoperative sufentanil consumption within the first 24 h, Visual Analogue Scale (VAS) for pain, postoperative equivalent milligrams of morphine (EMM), severity of postoperative nausea (PN) and vomiting (PV), prevalence of postoperative nausea and vomiting (PONV), use of antiemetics, time to first passage of flatus were compared by a two-tailed Student's t-test, Wilcoxon rank-sum tests or Fisher's exact tests. Repeated measures ANOVA was used to assess the effect of allocation of groups over time. RESULTS: The median [IQR] sufentanil consumption within 24 h was lower in group OF (4[4.5]) than in group C (6[8], mean difference [MD]=-2, 95% confidence interval [CI] [-4 to 0], P=0.029). The VAS scores at rest and during coughing at 6 h (P=0.009 at rest; P=0.002 during coughing), VAS scores during coughing at 2 h (P=0.013) and 4 h (P=0.008), EMM (P=0.026), severities of PN (P=0.003) and PV (P=0.003), and the mean time to first passage of flatus (P=0.017) was significantly less in group OF than that in group C. The prevalence of PONV (26.3% [group OF], 68.4% [group C], OR=0.31, 95% CI [0.158 to 0.589], P<0.001), use of antiemetics (5.3% [group OF], 28.9% [group C], OR=0.136, 95% CI [0.028 to 0.667], P=0.012) was also significantly different between groups. CONCLUSIONS: Compared to opioid-inclusive anesthesia during laparoscopic gynecologic surgery, OFA was associated with significant improvement in postoperative analgesia, reduced PONV incidence prevalence and severity, and faster first passage of flatus.

By regulating miR-182-5p/BCL10/CYCS, sufentanil reduces the apoptosis of umbilical cord mesenchymal stem cells caused by ropivacaine.

Sufentanil is a type of opioid analgesic and is usually used to facilitate painless labor in combination with the local anesthetic ropivacaine. One aim of the current study was to investigate the effects of sufentanil and ropivacaine on umbilical cord mesenchymal stem cells (UCMSCs). A second aim of this study was to determine whether sufentanil attenuated the cytotoxicity of ropivacaine in vitro. UCMSCs were divided into 3 groups: one was treated with ropivacaine at a concentration of 50, 100, 200, or 400 µg/mL, another was treated with sufentanil at a concentration of 0.5, 5, 50, or 500 nmol/L, and a third was treated with a combination of ropivacaine at a concentration of 200 µg/mL and sufentanil at a concentration of 0.5, 5, 50, or 500 nmol/L. Results indicated that cell proliferation decreased in cells treated with ropivacaine while it increased in cells treated with sufentanil. In addition, sufentanil limited the inhibitory effect of ropivacaine on UCMSC growth in a dose- and time-dependent manner. Combined treatment with ropivacaine at a concentration of 200 µg/mL and sufentanil at a concentration of 500 nmol/L decreased the proportion of dead and apoptotic UCMSCs, and fewer cells were arrested in the S phase compared to cells treated with ropivacaine. Sufentanil inhibited the apoptosis induced by ropivacaine by increasing miR-182-5p, which regulated the expression of mRNA of the pro-apoptotic genes B-cell lymphoma/leukemia 10 (BCL10) and cytochrome c, somatic (CYCS). Sufentanil also increased the expression of mRNA of anti-apoptotic genes. In short, ropivacaine inhibits the cell viability and induces the apoptosis of UCMSCs in vitro while sufentanil attenuates this apoptosis by regulating miR182-5p/BCL10/CYCS.

Effect of dexmedetomidine combined with sufentanil for post-caesarean section intravenous analgesia: a randomised, placebo-controlled study.

BACKGROUND: Few studies have investigated the use of dexmedetomidine in obstetric anaesthesia. OBJECTIVE: To evaluate the effect of dexmedetomidine combined with sufentanil for patient-controlled analgesia (PCA) after caesarean section under spinal anaesthesia. DESIGN: An interventional, randomised, double-blinded, placebo-controlled clinical study. SETTING: Department of Anaesthesiology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. PATIENTS: One hundred and twenty parturients (American Society of Anesthesiologists class 1 or 2) scheduled for elective caesarean delivery under spinal anaesthesia randomly allocated into three groups (n = 40 each). INTERVENTIONS: Group 1: physiological saline bolus after delivery and sufentanil PCA, Group 2: dexmedetomidine bolus (0.5 µg kg) after delivery and sufentanil PCA, Group 3: dexmedetomidine bolus (0.5 µg kg) after delivery and sufentanil with dexmedetomidine PCA (background infusion of 0.045 µg kg h with a bolus of 0.07 µg kg). MAIN OUTCOME MEASURES: The total consumption of sufentanil. Pain scores at rest evaluated with a visual analogue scale (VAS) and Ramsay sedation score (RSS) were recorded at the 4, 8 and 24 h after surgery. The patients' pain threshold (PTh) and pain tolerance threshold (PTTh) were measured before surgery and 1 h after initial study drug administration. Satisfaction scores were collected 24 h after surgery. RESULTS: Sufentanil consumption in group 3 was 43.9 ±â€Š19.2 µg, significantly lower than in group 1 (54.5 ±â€Š23.9 µg) and group 2 (56.3 ±â€Š20.6 µg) (P < 0.05). Compared with group 3, VAS was increased at 4, 8 and 24 h after surgery in groups 1 and 2 (P < 0.05); there was no difference between groups 1 and 2. PTh and PTTh were significantly increased 1 h after drug administration in groups 2 (1.59 ±â€Š0.45, 2.57 ±â€Š0.46 mA) and 3 (1.74 ±â€Š0.37, 2.56 ±â€Š0.48 mA) compared with group 1 (1.49 ±â€Š0.49, 2.42 ±â€Š0.62 mA) (P < 0.05). CONCLUSION: The combination of sufentanil and dexmedetomidine for PCA after caesarean section can reduce sufentanil consumption and improve parturients' satisfaction compared with sufentanil PCA alone. TRIAL REGISTRATION: ChiCTR-TRC-11001442.