Objective To investigate the influencing factors for low anterior resection syndrome(LARS)at one year after ileostomy reversal in patients who have undergone radical resection for rectal cancer,and to inform clinical interventions.Methods A retrospective cohort study was conducted on 312 patients who successfully underwent ileostomy reversal after radical resection for rectal cancer between January 2023 and January 2024 at 3 tertiary hospitals in Chongqing.Based on LARS scores at 1-year after stoma reversal,they were divided into a LARS group(score≥21)and a non-LARS group(score≤20).Clinical data were collected from the medical record system,including age,body mass index(BMI),sex,tumor size,tumor distance from the anal verge,T stage,N stage,date of low anterior resection,neoadjuvant therapy,postoperative chemotherapy,anastomotic leakage,and date of ileostomy reversal.Univariate analysis was used to screen potential influencing factors,and variables with P<0.2 were included in a multivariate logistic regression model.Binary stepwise regression analysis was applied to further analyze significant influencing factors for LARS at 1 year after ileostomy reversal.Results In the cohort,there were 127 patients assigned into the LARS group and 185 into the non-LARS group.The incidence of LARS at 1 year after ileostomy reversal was 40.70%,with mild cases accounting for 21.79%and severe ones for 18.91%,and a mean LARS score of 14.52±11.64.Multivariate logistic regression analysis showed that neoadjuvant therapy(yes vs no:OR=1.830,95%CI:1.088～3.089;P=0.023),tumor distance from anal verge≤5 cm(vs>5 cm:OR=2.044,95%CI:1.249～3.374;P=0.005),occurrence of anastomotic leakage(yes vs no:OR=7.470,95%CI:2.247～34.102;P=0.003),time to reversal(≥181 d vs 91～180 d:OR=2.297,95%CI:1.363～3.917;P=0.002),and N stage(N1～N2 vs N0:OR=1.650,95%CI:1.009～2.717;P=0.047)were significant influencing factors for LARS at 1 year after ileostomy reversal.Conclusion Our results suggest that anastomotic leakage,time to reversal≥181 d,tumor distance from anal verge≤5 cm,neoadjuvant therapy,and N stage N1～N2 are associated with the occurrence of LARS at 1 year after ileostomy reversal in patients following radical resection of rectal cancer.Clinical healthcare providers should implement early intervention and long-term follow-up for patients with high-risk factors both before and after stoma reversal.

Objective To analyze the changes of serum inhibin B(INHB),anti-Müllerian hormone(AMH)and sex hormone levels in patients with infertility caused by polycystic ovary syndrome(PCOS).Methods A total of 302 patients with infertility caused by PCOS admitted to the hospital from June 2021 to June 2023 were selected as the experimental group,and 300 healthy women of childbearing age with normal menstrual cycle were selected as the control group.The levels of serum INHB,AMH and sex hormone indexes[serum luteinizing hormone(LH),follicle stimulating hormone(FSH),prolactin(PRL),progesterone(P),testoster-one(T),estradiol(E2)]and homeostasis model assessment of insulin resistance(HOMA-IR)were observed and compared between the two groups.Results The serum levels of AMH,INHB and HOMA-IR in test group were significantly higher than those in control group,with statistical significance(P＜0.05).Serum levels of LH/FSH,PRL,T and P in experimental groups were significantly higher than those in control group,and serum E2 levels were significantly lower than those in control group,with statistical significance(P＜0.05).With the passage of treatment time,serum AMH,INHB,LH/FSH,PRL,T and P levels gradually decreased,and E2 levels gradually increased(P＜0.05).The area under the curve(AUC)of AMH and INHB combined detection in the diagnosis of infertility caused by PCOS was 0.905,which was higher than the AUC of AMH or INHB detection alone(P＜0.05).Serum AMH and INHB levels were positively correlated with FSH,LH,T and HOMA-IR,PRL,P(P＜0.05),and negatively correlated with serum E2 levels(P＜0.05).Conclusion The levels of AMH and INHB in serum of infertility patients caused by PCOS are significantly increased,and AMH and INHB are correlated with sex hormone levels.Detection of serum AMH,INHB and sex hormone levels is helpful for the diagnosis of infertility caused by PCOS.

Objective:To evaluate the relationship between immunoglobulin heavy chain-binding protein (BIP) and Na v1.8 in peripheral nerve in a rat model of neuropathic pain. Methods:Forty-four SPF healthy male Sprague-Dawley rats, weighing 210-260 g, were used in this study.Neuropathic pain was induced by chronic constriction injury (CCI) in anesthetized rats.The experiment was performed in two parts.Experiment Ⅰ Twenty rats were divided into 2 groups ( n=10 each) using a random number table method: sham operation group (group Sham) and group CCI.Experiment Ⅱ Twenty-four rats were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (group Sham), CCI plus normal saline group (group CCI+ NS) and CCI plus BIP inhibitor HA15 group (group CCI+ H). Starting from 4th day after surgery, 0.9% normal saline 1 ml was intraperitoneally injected in group CCI+ NS, and HA15 0.7 mg/kg was intraperitoneally injected in group H, once a day for 3 consecutive days.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before surgery and 3, 5 and 7 days after surgery (T 0-T 4), and the expression of BIP and Na v1.8 in dorsal root ganglion (DRG) and sciatic nerve was detected by Western blot on 7th day after completion of behavioral testing in two groups.The expression and colocalization of BIP and Na v1.8 in DRG and sciatic nerve were determined by immunofluorescence on 7th day after completion of behavioral testing in group Ⅰ, and the interaction between BIP and Na v1.8 was evaluated by co-immuno-precipitation. Results:Experiment Ⅰ Compared with group Sham, the MWT was significantly decreased, and TWL was shortened at T 1-T 4, the expression of Na v1.8 in DRG was down-regulated, the expression of BIP was up-regulated, and the expression of Na v1.8 and BIP in sciatic nerve was up-regulated in group CCI ( P<0.05), and BIP and Na v1.8 on the sciatic nerve were co-localized, BIP could co-precipitate Na v1.8 from DRG, and Na v1.8 could also coprecipitate BIP in group CCI.Experiment Ⅱ Compared with group Sham, the MWT was significantly decreased, and TWL was shortened at T 1-T 4, the expression of Na v1.8 in DRG was down-regulated, the expression of BIP was up-regulated, and the expression of Na v1.8 and BIP in sciatic nerve was up-regulated in group CCI+ NS ( P<0.05). Compared with group CCI+ NS, the MWT was significantly increased, and TWL was prolonged at T 3, 4, and the expression of Na v1.8 in DRG was down-regulated in group CCI+ H ( P<0.05). Conclusion:BIP can mediate the redistribution of Na v1.8 in peripheral nerve and is involved in the pathophysiological mechanism of neuropathic pain in rats.

OBJECTIVE: To explore whether bortezomib and a Bcl-2 inhibitor exhibit synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells. METHODS: MTT assay was used to determine the cytotoxicity of bortezomib in the absence or presence of Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) in Jurkat cells. The effects of drug treatment on the expression of Bcl-2 family proteins, LC3B, p62, ubiquitin, BiP/Grp78, p-JNK, p-p38 and CHOP proteins were examined by Western blotting. Flow cytometry was used to determine the effects of bortezomib and Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) on cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression levels of the key regulatory factors of unfolded protein reaction (UPR). A zebrafish xenograft model was used to study the anti-tumor effect of bortezomib, obatoclax and their combination in vivo. RESULTS: Bortezomib or Bcl-2 inhibitors alone inhibited the cell viability of Jurkat cells, but only obatoclax and bortezomib showed synergistic cytotoxicity and pro-apoptotic effect. Obatoclax, rather than AT-101 and ABT- 199, blocked autophagic flux in the cells evidenced by concomitant accumulation of LC3B-Ⅱ and p62. Both bortezomib and obatoclax alone caused accumulation of polyubiquinated proteins, and their combination showed a synergistic effect, which was consistent with their synergistic cytotoxicity. The dual blockade of proteasome and autophagy by the combination of bortezomib and obatoclax triggered unfolded protein response followed by cell apoptosis. Preventing UPS dysfunction by tauroursodeoxycholic acid (TUDCA) significantly attenuated the cytotoxicity and pro-apoptotic effect of bortezomib in combination with obatoclax. In zebrafish xenograft models, bortezomib combined with obatoclax significantly decreased tumor foci formation. CONCLUSIONS Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.
Antineoplastic Agents ; Apoptosis ; Bortezomib ; Cell Line, Tumor ; Drug Synergism ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Proteolysis ; Proto-Oncogene Proteins c-bcl-2 ; Pyrroles

Objective To determine the median effective dose (ED50) of oxycodone inhibiting responses to laryngeal mask airway (LMA) insertion when combined with propofol in the adult female patients.Methods Female patients,aged 18-60 yr,with body mass index of 18-24 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective gynecologic surgery,were included.ED50 of oxycodone was determined by up-and-down sequential technique.Anesthesia was induced by target-controlled infusion of propofol at target plasma concentration of 3.0 μg/ml.Oxycodone was injected at the initial dose of 0.11 mg/kg after the target effect-site and plasma concentrations were balanced.LMA was inserted at 5 min following injection.When the response to LMA insertion was positive,the concentration of oxycodone was increased/decreased in the next patient.The difference between the two successive doses was 0.02 mg/kg.LMA insertion response was defined as occurrence of swallowing,biting on the LMA and bucking and/or body movement during insertion.Probit analysis was used to calculate the ED50 and 95％ confidence interval of oxycodone inhibiting responses to LMA insertion when combined with propofol.Results The ED50 (95％ confidence interval) of oxycodone inhibiting responses to LMA insertion was 0.095 (0.080-0.108) mg/kg when combined with propofol.Conclusion The ED50 of oxycodone inhibiting responses to LMA insertion is 0.095 mg/kg when combined with propofol in the adult female patients.

Objective To evaluate the modifiying efficacy of pectoral nerve ( Pecs) block com-bined with general anesthesia in patients undergoing radical mastectomy. Methods A total of 60 American Society of Anesthesiologists physical status Ⅰ or Ⅱ female patients, aged 40-64 yr, weighing 50-70 kg, scheduled for elective radical mastectomy, were divided into 2 groups ( n= 30 each) using a random num-ber table method: general anesthesia group ( group GA) and Pecs block combined with general anesthesia group ( group PB+GA) . The patients in group PB+GA received Pecs block guided by ultrasound. After the needle was advanced to the pleura plane between the pectoralis major and minor, 0. 33％ ropivacaine 15 ml was injected, and 0. 33％ ropivacaine 30 ml was injected into the surface of the serratus anterior muscle at the level of the third rib. Anesthesia was induced by intravenous injection of midazolam, propofol, sufen-tanil and cisatracurium and maintained by target-controlled infusion of propofol and intermittent intravenous boluses of sufentanil and cisatracurium. Bispectral index value was maintained at 40-60. Patient-controlled intravenous analgesia was performed with sufentanil at the end of surgery. Immediately after anesthesia in-duction, at 30 min and 2 h after skin incision, and at 2, 6 and 24 h after operation, peripheral venous blood samples were collected for determination of the concentrations of plasma epinephrine by radioimmuno-assay, and the blood samples were collected from the end of the finger at the same time for determination of blood glucose concentrations. The consumption of intraoperative sufentanil, emergence time, pressing times of patient-controlled analgesia ( PCA) and development of nausea and vomiting within 24 h after operation were recorded. Results Compared with group GA, blood glucose and plasma epinephrine concentrations were significantly decreased, the intraoperative sufentanil consumption was reduced, the emergence time was shortened, the pressing times of PCA were decreased at 2, 6 and 24 h after operation ( P<0. 05) , and no significant change was found in the incidence of postoperative nausea and vomiting in group PB+GA ( P>0. 05). Conclusion When Pecs block combined with general anesthesia is used in the patients undergoing radical mastectomy, it is helpful in reducing the opioid consumption and more helpful in inhibiting postoper-ative stress responses and pain responses than general anesthesia alone.

Objective To investigate the safety and effectiveness of different intravenous anesthesia methods for pediatric ERCP . Methods Data of 45 children undergoing ERCP at the Affiliated Hangzhou Hospital of Nanjing Medical University from August 2013 to July 2016, including intravenous anesthesia,the procedure of ERCP, adverse reactions and the waking time were retrospectively studied. Results A total of 45 patients in two groups under intravenous anesthesia successfully underwent ERCP . Seventeen patients ( 37. 8%) whose body weights were over 20 kg and the duration of surgery was predicted less than 30 minutes received deep sedation without airway intubation. Twenty?eight patients ( 62. 2%) with an initial weight of less than 20 kg and the duration of surgery was predicted more than 30 minutes received general anesthesia with airway intubation. In patients with deep sedation, the mean time of waking was 7. 2±6. 3 minutes, body movement reaction occurred in 1 case ( 5. 9%) and with transient decreasing of pulse blood oxygen ( beyond 95%) occurred in 2 cases ( 11. 8%) . In patients receiving endotracheal anesthesia with intubation, the mean waking time was 10. 5±8. 7 minutes without adverse reactions associated with anesthesia. Conclusion Both deep sedation and general anesthesia with airway intubation are safe for pediatric ERCP. However, general anesthesia with airway intubation is an ideal method ensuring the airway safety and oxygen supply for children less than 20 kg undergoing first?time ERCP or the duration of surgery lasting over 30 minutes.

Objective To evaluate the effects of different concentrations of sevoflurane on the cognitive function in neonatal rats.Methods Twenty-four neonatal Sprague-Dawley rats of both sexes,aged 7 days,weighing 12-16g,were randomly divided into high concentration sevoflurane group (group Sev1),low concentration sevoflurane group (group Sev2) or control group (group C),with 8 rats in each group.Sev1 and Sev2 groups were exposed to 2％ and 4％ sevoflurane for 6h,respectively,and C group inhaled gas mixture composed of 30％ oxygen.At 2 and 8 weeks after exposure to sevoflurane,cognitive function was assessed using the open field test and Morris water maze test.Results In the open field test,no significant differences were observed among the three groups (P ＞ 0.05).Morris water-maze test showed that the escape latency was significantly prolonged,and the frequency of crossing the original platform and the time spent in the third quadrant were decreased at 2 weeks after exposure to sevoflurane in Sev1 group and at 2 and 8 weeks after exposure to sevoflurane in Sev2 group as compared with group C (P ＜ 0.05).Morris water-maze test showed that the escape latency was significantly prolonged,and the frequency of crossing the original platform and the time spent in the third quadrant were decreased at 2 and 8 weeks after exposure to sevoflurane in Sev2 group compared with Sev1 group (P ＜ 0.05).Conclusion Exposure to 4％ and 2％ sevoflurane for 6h both can induce cognitive decline and the decreasing effect is enhanced with the increasing concentration in the neonatal rats.