Effect of estradiol supplementation on luteal support following a significant reduction in serum estradiol levels after hCG triggering: a prospective randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the impact of adding 4 mg estradiol valerate to progesterone for luteal support on pregnancy rates in IVF cycles following a long protocol with reduced luteal serum estradiol levels post-hCG triggering. DESIGN, SETTING, AND PARTICIPANTS: The prospective randomized controlled trial was conducted at a public tertiary hospital reproductive center with 241 patients who experienced a significant decrease in serum estrogen levels post-oocyte retrieval. INTERVENTIONS: Participants received either a daily 4 mg dose of estradiol valerate in addition to standard progesterone or standard progesterone alone for luteal support. RESULTS: The ongoing pregnancy rate did not show a significant difference between the E2 group and the control group (56.6% vs. 52.2%, with an absolute rate difference (RD) of 4.4%, 95% CI -0.087 to 0.179, P = 0.262). Similarly, the live birth rate, implantation rate, clinical pregnancy rate, early abortion rate, and severe OHSS rate were comparable between the two groups. Notably, the E2 group had no biochemical miscarriages, contrasting significantly with the control group (0.0% vs. 10.7%, RD -10.7%, 95% CI -0.178 to -0.041, P = 0.000). In the blastocyst stage category, the clinical pregnancy rate was notably higher in the E2 group compared to the control group (75.6% vs. 60.8%, RD 14.9%, 95% CI 0.012 to 0.294, P = 0.016). CONCLUSION: Adding 4 mg estradiol valerate to progesterone for luteal support does not affect the ongoing pregnancy rate in embryo transfer cycles using a long protocol with a significant decrease in serum estradiol levels after hCG triggering. However, it may reduce biochemical miscarriages and positively impact clinical pregnancy rates in blastocyst embryo transfer cycles. TRIAL REGISTRATION: ChiCTR1800020342.

Risk factors of textbook outcome in laparoscopic pancreatoduodenectomy: results from a prospective high-volume center study.

OBJECTIVE: Achieving textbook outcome (TO) implies a smooth recovery post-operation without specified composite complications. This study aimed to evaluate TO in laparoscopic pancreaticoduodenectomy (LPD) and identify independent risk factors associated with achieving TO. METHODS: We conducted a retrospective analysis of data from a randomized controlled trial on LPD at West China Hospital (ChiCTR1900026653). Patients were categorized into the TO and non-TO groups. Perioperative variables were compared between these groups. Multivariate logistic regression was utilized to identify the risk factors. RESULTS: A total of 200 consecutive patients undergoing LPD were included in this study. TO was achieved in 82.5% (n = 165) of the patients. Female patients (OR: 2.877, 95% CI: 1.219-6.790; P = 0.016) and those with a hard pancreatic texture (OR: 2.435, 95% CI: 1.018-5.827; P = 0.046) were associated with an increased likelihood of achieving TO. CONCLUSIONS: TO can be achieved in more than 80% of patients in a high-volume LPD center. Independent risk factors associated with achieving TO included gender (male) and pancreatic texture (soft).

PLEK2 promotes migration and invasion in pancreatic ductal adenocarcinoma by MMP1 through IL-17 pathway.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis primarily due to metastasis. Accumulating evidence suggests that PLEK2 acts as an oncogene in various tumors. This study aimed to investigate the effects of PLEK2 on PDAC. Expression analysis of PLEK2 was conducted using qRT-PCR, Western blot, and immunohistochemistry in PDAC. Wound healing and transwell assays were performed to evaluate the impact of PLEK2 on cell migration and invasion. A xenograft tumor model was employed to assess the in vivo proliferation of PLEK2. Additionally, the downstream pathway of PLEK2 was analyzed through RNA-seq and confirmed by Western blot analysis. The results demonstrated the upregulation of PLEK2 expression in tumor specimens. High PLEK2 expression was significantly associated with poor overall survival and advanced TNM stages. Correlation analyses revealed positive correlations between PLEK2 and TGF-ß, EGFR, and MMP1. Wound healing and transwell assays demonstrated that PLEK2 promoted PDAC cell migration and invasion, potentially through the activation of the epithelial-to-mesenchymal transition process. The in vivo experiment further confirmed that PLEK2 knockdown suppressed tumor growth. RNA-seq analysis revealed PLEK2's regulation of MMP1 and activation of p-ERK and p-STAT3, which were verified by Western blot analysis. Overall, the present study suggests that PLEK2 may play a tumor-promoting role in PDAC. These findings provide valuable insights into the molecular mechanisms of pancreatic cancer and highlight the potential of PLEK2 as a therapeutic target.

Artificial intelligence automated surgical phases recognition in intraoperative videos of laparoscopic pancreatoduodenectomy.

BACKGROUND: Laparoscopic pancreatoduodenectomy (LPD) is one of the most challenging operations and has a long learning curve. Artificial intelligence (AI) automated surgical phase recognition in intraoperative videos has many potential applications in surgical education, helping shorten the learning curve, but no study has made this breakthrough in LPD. Herein, we aimed to build AI models to recognize the surgical phase in LPD and explore the performance characteristics of AI models. METHODS: Among 69 LPD videos from a single surgical team, we used 42 in the building group to establish the models and used the remaining 27 videos in the analysis group to assess the models' performance characteristics. We annotated 13 surgical phases of LPD, including 4 key phases and 9 necessary phases. Two minimal invasive pancreatic surgeons annotated all the videos. We built two AI models for the key phase and necessary phase recognition, based on convolutional neural networks. The overall performance of the AI models was determined mainly by mean average precision (mAP). RESULTS: Overall mAPs of the AI models in the test set of the building group were 89.7% and 84.7% for key phases and necessary phases, respectively. In the 27-video analysis group, overall mAPs were 86.8% and 71.2%, with maximum mAPs of 98.1% and 93.9%. We found commonalities between the error of model recognition and the differences of surgeon annotation, and the AI model exhibited bad performance in cases with anatomic variation or lesion involvement with adjacent organs. CONCLUSIONS: AI automated surgical phase recognition can be achieved in LPD, with outstanding performance in selective cases. This breakthrough may be the first step toward AI- and video-based surgical education in more complex surgeries.

[Impact of Liparis nervosa extract on neuroinflammation mediated by LPS-induced BV-2 microglial cells and its bioactive components analysis].

To investigate the impact and potential mechanisms of extracts from different parts of Liparis nervosa on neuroinflammation by lipopolysaccharide(LPS)-induced BV-2 microglial cells. The materials of L. nervosa were subjected to crushing, ethanol extraction, and concentration to obtain an alcohol extract. Subsequently, the extract was further extracted to obtain petroleum ether extract, ethyl acetate extract, N-butanol extract, and aqueous phase extract. The ethyl acetate extract was separated into distillate(1)-(6)using D101 macroporous resin column chromatography. The experiment was divided into control group, LPS model group, L. nervosa extract group, and LPS + L. nervosa group. LPS was utilized to induce a neuroinflammatory cell model in BV-2 microglial cells. The Griess test was utilized for detecting the production of nitric oxide(NO) in the cell supernatant. Cell viability was detected by MTT assay. The release of interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α) in the cell supernatant was quantified using ELISA.RT-qPCR was utilized to assess the m RNA levels of pro-inflammatory cytokines inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2), interleukin( IL)-6, IL-1ß, and TNF-α. The protein expression of i NOS, COX-2, nuclear factor kappa-B p65(p65), p-p65, extracellular signal-regulated kinase(ERK), p-ERK, c-jun N-terminal kinase(JNK), p-JNK, p38 mitogen-activated protein kinase(p38), and p-p38 MAPK(p-p38) were also evaluated by Western blot. The chemical composition of active substances in L. nervosa was analyzed using the UHPLC-Q-Exactive Orbitrap technology and literature comparison. Our findings indicate that extracts from different parts of L. nervosa exhibit a significant reduction in the release of NO from LPS-induced BV-2 microglial cells.Specifically, the ethyl acetate extract demonstrates the most notable inhibitory effect without causing cell toxicity. Additionally, the distillate(6) extracted from the ethyl acetate exhibits a reduction in the m RNA and protein levels of i NOS, COX-2, IL-6, IL-1ß, and TNF-α in a dose-dependent manner, and it inhibits the protein expression of p-p65, p-ERK, p-p38, and p-JNK in LPS-induced BV-2 microglial cells. A total of 79 compounds in the distillate(6) were identified by mass spectrometry, including 12 confirmed compounds with anti-inflammatory effects. This study confirmed the remarkable efficacy of L. nervosa extract in the treatment of neuroinflammation, which may be achieved through the inhibition of NF-κB and MAPK signaling pathways.

Interim analysis of short-term outcomes after laparoscopic spleen-preserving distal pancreatectomy with or without preservation of splenic vessels: a randomised controlled trial.

BACKGROUND: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) is a widely adopted surgical approach for benign and low-grade malignant neoplasms of the distal pancreas. The Kimura and Warshaw techniques represent two principal strategies, yet it still needs to be determined which one is superior. Our investigation aimed to evaluate the clinical outcomes associated with each technique. MATERIALS AND METHODS: This single-center, parallel-group, patient-blinded randomized controlled trial (RCT) was conducted at the XXXXX University. Stratified block randomization was utilized to enroll 114 patients starting in March 2022, with an interim analysis of short-term outcomes scheduled after 45%-50% of participant enrollment. Patients were randomized to receive LSPDP via either the Kimura or Warshaw technique. The primary endpoint was intraoperative blood loss, while secondary endpoints included a range of outcomes from composite outcome to quality of life, as quantified by the EQ-5D-5L. RESULTS: From March 2022 to November 2023, 53 patients were randomly allocated to the Kimura (n=25) or Warshaw (n=28) groups for LSPDP. Baseline characteristics and postoperative outcomes were similar between the groups, such as pancreatic fistula incidence, EQ-5D-5L index scores, and delayed gastric emptying rates. Per-protocol (PP) analysis revealed that the Kimura group experienced significantly less blood loss (52.5±51.6 mL vs. 91.7±113.5 mL, P=0.007) and a reduced rate of composite outcome (23.8% vs. 56.7%, P=0.019), but incurred higher costs in the Warshaw group (¥56,227.4±¥7,027.0 vs. ¥63,513.8±¥12,944.5, P=0.013). Splenic infarction rates were higher in the Warshaw group, though not statistically significant (ITT: 39.3% vs. 12.5%, P=0.058; PP: 36.7% vs. 14.3%, P=0.113), without necessitating intervention. Neither group experienced postpancreatectomy haemorrhage, 90-day mortality, or ICU admissions, and all postoperative complications were mild (Clavien-Dindo Grade

Impact of an AI-Based laparoscopic cholecystectomy coaching program on the surgical performance: a randomized controlled trial.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the gold standard for treating symptomatic gallstones but carries inherent risks like bile duct injury (BDI). While critical view of safety (CVS) is advocated to mitigate BDI, its real-world adoption is limited. Additionally, significant variations in surgeon performance impede procedural standardization, highlighting the need for a feasible, innovative, and effective training approach. The aim of this study is to develop an Artificial Intelligence (AI)-assisted coaching program for LC to enhance surgical education and improve surgeon's performance. MATERIALS AND METHODS: We conducted a multi-center, randomized controlled trial from May 2022 to August 2023 to assess the impact of an AI-based coaching program, SmartCoach, on novice performing LC. Surgeons and patients meeting specific inclusion criteria were randomly assigned to either a coaching group with AI-enhanced feedback or a self-learning group. The primary outcome was assessed using the Laparoscopic Cholecystectomy Rating Form (LCRF), with secondary outcomes including surgical safety, efficiency, and adverse events. Statistical analyses were performed using SPSS, with significance set at P-value less than 0.05. RESULTS: Between May 2022 and August 2023, 22 surgeons were initially enrolled from 10 hospitals, with 18 completing the study. No demographic differences were noted between coaching and self-learning groups. In terms of surgical performance (LCRF scores), the coaching group showed significant improvement over time (31 to 40, P=0.008), outperforming the self-learning group by study end (40 vs 38, P=0.032). Significant improvements in CVS achievement were also noted in the coaching group (11% to 78%, P=0.021). Overall, the coaching program was well-received, outpacing traditional educational methods in both understanding and execution of CVS and participants in the intervention group expressed strongly satisfaction with the program. CONCLUSIONS: The AI-assisted surgical coaching program effectively improved surgical performance and safety for novice surgeons in LC procedures. The model holds significant promise for advancing surgical education.

Single-incision plus one port laparoscopic pancreaticoduodenectomy with major venous resection and reconstruction for pancreatic cancer with video recordings.

Laparoscopic pancreaticoduodenectomy (LPD) with superior mesenteric/portal vein (SMV/PV) resection and reconstruction was the most technically challenging procedure and had been rarely reported. However, single-incision plus one-port LPD (SILPD +1) with SMV/PV resection and reconstruction has never been reported. In this study, we will demonstrate the feasibility, safety, key surgical procedure, and long-term outcomes for SILPD +1 with SMV/PV resection and reconstruction using video evidence. Two cases of SILPD +1 with SMV/PV wedge resection were carried out by the authors. There was no tumor recurrence during the one-year follow-up. It is worth noting that skilled laparoscopic technicians are necessary to safely complete the procedure with good short-term and long-term outcomes.

CDK4/6 inhibition sensitizes MEK inhibition by inhibiting cell cycle and proliferation in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to most chemotherapy drugs, leading to poor chemotherapy efficacy. Recently, Trametinib and Palbociclib have promising prospects in the treatment of pancreatic cancer. This article aims to explore the effects of Trametinib on pancreatic cancer and address the underlying mechanism of resistance as well as its reversal strategies. The GDSC (Genomics of Drug Sensitivity in Cancer) and CTD2 (Cancer Target Discovery and Development) were utilized to screen the potential drug candidate in PDAC cell lines. The dose-increase method combined with the high-dose shock method was applied to induce the Trametinib-resistant PANC-1 and MIA PaCa-2 cell lines. The CCK8 proliferation assay, colony formation assay, flow cytometry, and western blot were conducted to verify the inhibitory effect of Trametinib and Palbociclib. RNA-seq was performed in resistant PDAC cell lines to find the differential expression genes related to drug resistance and predict pathways leading to the reversal of Trametinib resistance. The GDSC and CTD2 database screening revealed that Trametinib demonstrates a significant inhibitory effect on PDAC. We found that Trametinib has a lower IC50 than Gemcitabine in PDAC cell lines. Both Trametinib and Gemcitabine can decrease the proliferation capacity of pancreatic cells, induce cell cycle arrest, and increase apoptosis. Simultaneously, the phosphorylation of the AKT and ERK pathways were inhibited by the treatment of Trametinib. In addition, the RNA-seq of Trametinib-induced resistance PDAC cell lines reveals that the cyclin-dependent kinase (CDK)-RB-E2F regulatory axis and G2/M DNA damage checkpoint might lead the drug resistance. Besides, the combination of Trametinib with Palbociclib could inhibit the proliferation and cell cycle of both resistant cells lines and also restore the sensitivity of drug-resistant cells to Trametinib. Last but not least, the interferon-α and interferon-γ expression were upregulated in resistance cell lines, which might lead to the reversal of drug resistance. The study shows Trametinib has a critical inhibitory effect on PDAC. Besides, the combination of Trametinib with Palbociclib can inhibit the proliferation of PDAC-resistant cells.

Associations of iron metabolism and inflammation with all-cause and cardiovascular mortality in a large NHANES community sample: Moderating and mediating effects.

BACKGROUND AND AIMS: This study aimed to assess the associations between serum iron concentration, C-reactive protein (CRP) concentration and the risk of all-cause mortality and cardiovascular mortality in the general population and to explore potential mediating and moderating effects. METHODS AND RESULTS: This study analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999-2010, encompassing 23,634 participants. Cox proportional hazards regression models were employed to investigate the independent associations of serum iron and CRP with all-cause and cardiovascular mortality. Moderation and mediation analyses explored the moderating effect of CRP on the association between the serum iron concentration and all-cause and cardiovascular mortality, and the mediating role of the serum iron concentration in the association between the CRP concentration and all-cause and cardiovascular mortality. After multivariate adjustments in the Cox model, serum iron and CRP levels were independently correlated with both all-cause and cardiovascular mortality risk. Moderation analyses revealed a more pronounced correlation between the serum iron concentration and both all-cause and cardiovascular mortality in participants with higher CRP levels. Mediation analysis indicated that the serum iron concentration partly mediated the impact of CRP on the risk of all-cause mortality (13.79%) and cardiovascular mortality (24.12%). CONCLUSION: Serum iron and CRP are independently associated with all-cause and cardiovascular mortality. Moreover, the associations between serum iron concentrations and both all-cause and cardiovascular mortality are more pronounced in individuals with elevated CRP. Serum iron partially mediates the effect of CRP on all-cause and cardiovascular mortality.

Independent external validation and comparison of existing pancreatic fistula risk scores after laparoscopic pancreaticoduodenectomy with Bing's pancreaticojejunostomy.

BACKGROUND: The fistula risk score (FRS) is the widely acknowledged prediction model for clinically relevant postoperative pancreatic fistula (CR-POPF). In addition, the alternative FRS (a-FRS) and updated alternative FRS (ua-FRS) have been developed. This study performed external validation and comparison of these 3 models in patients who underwent laparoscopic pancreaticoduodenectomy (LPD) with Bing's pancreaticojejunostomy. METHODS: The FRS total points and predictive probabilities of a-FRS and ua-FRS were retrospectively calculated using patient data from a completed randomized controlled trial. Postoperative pancreatic fistula (POPF) and CR-POPF were defined according to the 2016 International Study Group of Pancreatic Surgery criteria. The correlations of the 4 risk items of the FRS model with CR-POPF and POPF were analyzed and represented using the Cramer V coefficient. The performance of the 3 models was measured using the area under the curve (AUC) and calibration plot and compared using the DeLong test. RESULTS: This study enrolled 200 patients. Pancreatic texture and pathology had discrimination for CR-POPF (Cramer V coefficient: 0.180 vs 0.167, respectively). Pancreatic duct diameter, pancreatic texture, and pathology had discrimination for POPF (Cramer V coefficient: 0.357 vs 0.322 vs 0.257, respectively). Only the calibration of a-FRS predicting CR-POPF was good. The differences among the AUC values of the FRS, a-FRS, and ua-FRS were not statistically significant (CR-POPF: 0.687 vs 0.701 vs 0.710, respectively; POPF: 0.733 vs 0.741 vs 0.750, respectively). After recalibrating, the ua-FRS got sufficient calibration, and the AUC was 0.713 for predicting CR-POPF. CONCLUSION: For LPD cases with Bing's pancreaticojejunostomy, the 3 models predicted POPF with better discrimination than predicting CR-POPF. The recalibrated ua-FRS had sufficient discrimination and calibration for predicting CR-POPF.

Textbook oncologic outcomes are associated with increased overall survival in patients with pancreatic head cancer after undergoing laparoscopic pancreaticoduodenectomy.

BACKGROUND: Textbook oncologic outcomes (TOO) have been used to evaluate long-term oncologic outcomes for patients after pancreaticoduodenectomy (PD) but not laparoscopic pancreaticoduodenectomy (LPD). The aim of the study was to assess the prognostic value of TOO for patients with pancreatic head cancer undergoing LPD and discuss the risk factors associated with achieving TOO. METHODS: Patients with pancreatic head cancer who underwent LPD in West China Hospital from January 2015 to May 2022 were consecutively enrolled. TOO was defined as achieving R0 resection, examination of ≥ 12 lymph nodes, no prolonged length of stay, no 30-day readmission/death, and receiving adjuvant chemotherapy. Survival analysis was used to determine the prognostic value of a TOO on overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify the risk factors of a TOO. The rates of a TOO and of each indicator were compared in patients who suffered or not from delayed gastric emptying (DGE). RESULTS: A total of 44 (25.73%) patients achieved TOO which was associated with improved median OS (TOO 32 months vs. non-TOO 20 months, P = 0.034) and a better RFS (TOO 19 months vs. non-TOO 13 months, P = 0.053). Patients suffering from DGE [odds ratio (OR) 4.045, 95% CI 1.151-14.214, P = 0.029] were independent risk factors for TOO. In addition, patients with DGE after surgery had a significantly lower rate of TOO (P = 0.015) than patients without DGE. CONCLUSIONS: As there were significant differences between patients who achieved TOO or not, TOO is a good indicator for long-term oncologic outcomes in patients with pancreatic head cancer after undergoing LPD. DGE is the risk factor for achieving TOO, so it is important to prevent the DGE after LPD to improve the rate of TOO.

Extended pancreatic neck transection versus conventional pancreatic neck transection during laparoscopic pancreaticoduodenectomy (LPDEXCEPT): protocol for a multicentre superiority randomised controlled trial.

INTRODUCTION: Postoperative pancreatic fistula (POPF) remains one of the most severe complications of laparoscopic pancreaticoduodenectomy (LPD). Theoretically, transecting the pancreatic neck more distally has both advantages (more blood supply, and more central pancreatic duct) and disadvantages (maybe smaller the pancreatic duct) in preventing POPF. This theoretical contradiction pushed us to organise this trial to explore the impact of the level of pancreatic transection in clinical practice. We conduct this randomised trial with the hypothesis that extended pancreatic neck transection has superiority to conventional pancreatic neck transection. METHODS AND ANALYSIS: The LPDEXCEPT (Extended pancreatic neck transection versus conventional pancreatic neck transection during laparoscopic pancreaticoduodenectomy) trial is a multicentre, randomised-controlled, open-label, superiority trial in 4 centres whose annual surgical volume for LPD is more than 25 cases with pancreatic surgeons who had completed their learning curve. A total of 154 patients who meet the inclusive and exclusive criteria are randomly allocated to the extended pancreatic neck transection group or conventional pancreatic neck transection group in a 1:1 ratio. The stratified randomised block design will be applied, with stratified factors are surgical centre and the diameter of the main pancreatic duct measured by preoperative CT scan (preMPD). The primary outcome is the incidence of the clinically relevant pancreatic fistula. ETHICS AND DISSEMINATION: Ethics Committee on Biomedical Research of West China Hospital of Sichuan University has approved this trial in March 2023 (approval no. 2023-167). Results of this trial will be published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: NCT05808894.

Luteal phase support of intramuscular progesterone associated with lower hypertensive disorders of pregnancy as compared to vaginal progesterone: A cohort study.

OBJECTIVE: To compare the hypertensive disorders of pregnancy (HDP) risk between vaginal and intramuscular (IM) progesterone in programmed frozen-thawed embryo transfer (FET) cycles. METHODS: This was a retrospective cohort study at a tertiary hospital, and only women who achieved ongoing pregnancy after programmed FET between January 2018 and June 2022 were included. Women with chronic hypertension before pregnancy or with history of gestational hypertension or pre-eclampsia in previous pregnancies were excluded. All women were divided into IM progesterone or vaginal progesterone groups according to the route of progesterone supplementation. Follow-up information on obstetric complications and neonatal outcomes were obtained by telephonic interviews. The primary outcome was HDP. Association between routes of progesterone supplementation and HDP was assessed by subgroup analysis and multivariable logistic regression. RESULTS: A total of 5891 programmed FET cycles (3196 IM progesterone cycles and 2695 vaginal progesterone cycles) were included in the analysis. The prevalence of HDP in the IM progesterone group was significantly lower than that of the vaginal progesterone group (6.54% vs 9.17%, P < 0.001). Therein, the prevalence of gestational hypertension (3.57% vs 4.94%, P = 0.009) and pre-eclampsia (2.97% vs 4.23%, P = 0.009) in the IM progesterone group were all significantly lower as compared to the vaginal progesterone group. According to subgroup analysis, IM progesterone was associated with lower HDP risk in all subgroups. The logistic regression analysis showed that the IM progesterone cycles were associated with lower risk of HDP compared to vaginal progesterone cycles (adjusted odds ratio 0.66, 95% CI: 0.54-0.80, P < 0.001). CONCLUSION: Among women undergoing programmed FET cycles, progesterone supplementation with IM progesterone was associated with reduced HDP risk compared to vaginal progesterone.

Decoding surgical skill: an objective and efficient algorithm for surgical skill classification based on surgical gesture features -experimental studies.

BACKGROUND: Various surgical skills lead to differences in patient outcomes and identifying poorly skilled surgeons with constructive feedback contributes to surgical quality improvement. The aim of the study was to develop an algorithm for evaluating surgical skills in laparoscopic cholecystectomy based on the features of elementary functional surgical gestures (Surgestures). MATERIALS AND METHODS: Seventy-five laparoscopic cholecystectomy videos were collected from 33 surgeons in five hospitals. The phase of mobilization hepatocystic triangle and gallbladder dissection from the liver bed of each video were annotated with 14 Surgestures. The videos were grouped into competent and incompetent based on the quantiles of modified global operative assessment of laparoscopic skills (mGOALS). Surgeon-related information, clinical data, and intraoperative events were analyzed. Sixty-three Surgesture features were extracted to develop the surgical skill classification algorithm. The area under the receiver operating characteristic curve of the classification and the top features were evaluated. RESULTS: Correlation analysis revealed that most perioperative factors had no significant correlation with mGOALS scores. The incompetent group has a higher probability of cholecystic vascular injury compared to the competent group (30.8 vs 6.1%, P =0.004). The competent group demonstrated fewer inefficient Surgestures, lower shift frequency, and a larger dissection-exposure ratio of Surgestures during the procedure. The area under the receiver operating characteristic curve of the classification algorithm achieved 0.866. Different Surgesture features contributed variably to overall performance and specific skill items. CONCLUSION: The computer algorithm accurately classified surgeons with different skill levels using objective Surgesture features, adding insight into designing automatic laparoscopic surgical skill assessment tools with technical feedback.

Effect of miR-206 on lower limb ischemia-reperfusion injury in rat and its mechanism.

Lower limb ischemia-reperfusion is a common pathological process during clinical surgery. Because lower limb ischemia-reperfusion usually aggravates ischemia-induced skeletal muscle tissue injury after lower limb ischemia-reperfusion, it also causes remote organ heart, intestine, liver, lung and other injuries, and there is no effective clinical treatment for lower limb ischemia-reperfusion injury, so it is urgent to study its injury mechanism. In this study, the rat model of lower limb ischemia-reperfusion was established by clamping the femoral artery with microarterial clips, and the wall destruction such as intimal injury, cell edema, collagen degeneration, neutrophil infiltration, and elastic fiberboard injury of the femoral artery wall was detected. The expression of inflammatory factors was detected by immunohistochemistry. miR-206 preconditioning was used to observe the expression of inflammatory factors, redox status and apoptosis in the vascular wall of rats after acute limb ischemia-reperfusion. Our findings suggest that vascular endothelial cell edema increases, wall thickening, neutrophil infiltration, and elastic fiber layer damage during IRI. Inflammatory factor expression was increased in femoral artery tissue, and miR-206 expression levels were significantly down-regulated. Further studies have found that miR-206 attenuates lower limb IRI by regulating the effects of phase inflammatory factors. In this study, we investigated the effect of miR-206 on inflammatory factors and its possible role in the development of lower limb IRI, providing new research ideas for the regulatory mechanism of lower limb IRI, and providing a certain theoretical basis for the treatment of lower limb ischemia-reperfusion injury after surgery or endovascular intervention.

Effectiveness of atosiban in women with previous single implantation failure undergoing frozen-thawed blastocyst transfer: study protocol for a randomised controlled trial.

BACKGROUND: Uterine contractions may interfere with embryo implantation in assisted reproductive technology. To reduce these contractions and improve success rates, the oxytocin antagonist atosiban has been suggested for administration during embryo transfer. The aim of this study is to evaluate the effectiveness of atosiban in increasing live birth rates among women who have previously experienced a single implantation failure and are scheduled for single blastocyst transfer. METHODS AND ANALYSIS: We conduct a single-centre randomised controlled study comparing atosiban and placebo in women undergoing a single blastocyst transfer with a previous failed blastocyst transfer. Women with endocrine or systemic illnesses, recurrent miscarriages, uterine malformations or fibroids, untreated hydrosalpinx, endometriosis (stage III or IV) or uterine fibroids, as well as women undergoing preimplantation genetic testing, are ineligible. The primary outcome is live birth resulting from the frozen-thawed embryo transfer. Secondary outcomes include biochemical/clinical pregnancy, miscarriage, ectopic pregnancy, multiple pregnancies as well as maternal and perinatal outcomes. We plan to recruit 1100 women (550 women per group). This will allow us to demonstrate or refute an increase in live birth rate from 40% to 50%. Data analysis will follow the intention-to-treat principle. We will measure patterns of uterine peristalsis which will allow subgroup analysis for women with or without uterine peristalsis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of Northwest Women's and Children's Hospital (No. SZ2019001). Written informed consent will be obtained from each participant before randomisation. The results of the trial will be presented at scientific meetings and reported in publications. TRIAL REGISTRATION NUMBER: ChiCTR1900022333.

Initial experience of single-incision plus one port total laparoscopic pancreaticoduodenectomy.

BACKGROUND: The use of single-incision plus one-port laparoscopic pancreaticoduodenectomy (SILPD + 1) has been never reported, and its safety and efficacy remain unknown. This study aimed to evaluate the short-term outcomes of SILPD + 1 compared with those of conventional laparoscopic pancreaticoduodenectomy (CLPD). METHOD: Fifty-seven cases of laparoscopic pancreaticoduodenectomy (LPD) were performed between November 2021, and March 2022. Among them, 10 cases of LPD were performed using a single-incision plus one-port device. Based on the same inclusion and exclusion criteria, 47 cases of LPD performed using traditional 5-trocar were included as a control group. The patient's demographic characteristics, intraoperative, and postoperative variables were prospectively collected and retrospectively analyzed. RESULTS: Three men and seven women were included in the SILPD + 1 group. All baseline parameters of both groups were comparable, except for age. Patients were younger in the SILPD + 1 group (47.2 ± 18.3 years vs. 60.6 ± 11.7 years, P = 0.05) than that in the CLPD group. Compared with the CLPD group, median operation time (222.5 (208.8-245.0) vs. 305.0 (256.0-37.0) min, P < 0.001) was shorter, median postoperative VAS scores on days 1-3 were lower, and median cosmetic score (21.0 (19.0-23.5) vs. 17.0 (16.0-20.0), P = 0.026) was higher one month after the surgery in the SILPD + 1 group. The estimated blood loss, conversion rate, blood-transfusion rate, exhaust time, time of drainage tube removal, postoperative hospital stays, and perioperative complications were comparable between the two groups. CONCLUSION: In a high-volume LPD center, SILPD + 1 is safe and feasible for well-selected patients without increasing the operation time and complications. It even has the advantages of reduced postoperative pain and improved cosmetic results.

Laparoscopic transduodenal ampullectomy: initial experience from a single center.

Background: Laparoscopic transduodenal ampullectomy (LTDA) is a function-preserving surgery for pre-malignant tumors of the ampulla of Vater (AoV). However, it is technically challenging, and only a few case reports of LTDA are available in the literature. Methods: A total of 43 cases of pre-malignant tumors of AoV were operated in West China Hospital, Sichuan University between January 2017 and July 2022. Among these patients, 9 patients (group 1) underwent LTDA, 19 patients (group 2) underwent laparoscopic pancreaticoduodenectomy (LPD), and 15 patients (group 3) underwent open transduodenal ampullectomy (OTDA). Prospective collection and retrospective analysis of the demographic characteristics, intraoperative variables, and postoperative variables were carried out. Results: The patients in the three groups were comparable in terms of sex, age, body mass index, tumor size, and preoperative blood tests. In comparison to the patients in group 2, the patients in group 1 were found to require less operative time (159.7 ± 47.5 min vs. 298.1 ± 62.6, p < 0.01) and suffered lower blood losses (23.3 ± 16.7 ml vs. 156.8 ± 112.1, p = 0.002) and complications. Moreover, the postoperative hospital stays (POHS) were significantly shorter for patients in group 1 (9.0 ± 5.3 days vs. 15.5 ± 7.3 days, p = 0.04). Compared to patients who underwent OTDA, the patients in LTDA suffered from less blood loss. The operative time and post-operative details were comparable. Conclusion: Therefore, LTDA was found to be safe and feasible in the setting of pre-malignant tumors of AoV in well-selected patients. However, multidisciplinary preoperative planning is essential before the surgery.

Multiple RNA Profiling Reveal Epigenetic Toxicity Effects of Oxidative Stress by Graphene Oxide Silver Nanoparticles in-vitro.

Introduction: The increasing industrial and biomedical utilization of graphene oxide silver nanoparticles (GO-AgNPs) raises the concern of nanosafety: exposure to the AgNPs or GO-AgNPs increases the generation of reactive oxygen species (ROS), causes DNA damage and alters the expression of whole transcriptome including mRNA, miRNA, tRNA, lncRNA, circRNA and others. Although the roles of different RNAs in epigenetic toxicity are being studied during the last decade, but still we have little knowledge about the role of circle RNAs (circRNAs) in epigenetic toxicity. Methods: Rabbit fetal fibroblast cells (RFFCs) were treated with 0, 8, 16, 24, 32 and 48 µg/mL GO-AgNPs to test the cell viability and 24 µg/mL GO-AgNPs was selected as the experimental dose. After 24 h treatment with 24 µg/mL GO-AgNPs, the level of ROS, malondialdehyde (MDA), superoxide dismutase (SOD), intracellular ATP, glutathione peroxidase (GPx), and glutathione reductase (Gr) were measured in the RFFCs. High-throughput whole transcriptome sequencing was performed to compare the expression of circRNAs, long non-coding RNAs (lncRNA) and mRNA between 24 µg/mL GO-AgNPs-treated RFFCs and control cells. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to validate the accuracy of circRNA sequencing data. Bioinformatics analyses were performed to reveal the potential functional roles and related pathways of differentially expressed circRNAs, lncRNA and mRNA and to construct a circRNA-miRNA-mRNA interaction network. Results: We found that 57 circRNAs, 75 lncRNAs, and 444 mRNAs were upregulated while 35 circRNAs, 21 lncRNAs, and 186 mRNAs were downregulated. These differentially expressed genes are mainly involved in the transcriptional mis-regulation of cancer through several pathways: MAPK signaling pathway (circRNAs), non-homologous end-joining (lncRNAs), as well as PPAR and TGF-beta signaling pathways (mRNAs). Conclusion: These data revealed the potential roles of circRNAs in the GO-AgNPs induced toxicity through oxidative damage, which would be the basis for further research to determine their roles in the regulation of different biological processes.