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.

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.

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.

Embryo development and live birth in women with one previously failed full IVF/ICSI cycle.

PURPOSE: To evaluate the embryological and pregnancy outcomes of women who failed in their first IVF treatment if they attempted a second cycle. METHODS: For evaluating the embryological outcomes, the study cohort included 1,227 women who failed to obtain a live birth after the initial IVF cycle from September 2018 to August 2021 and returned for a second attempt. To evaluate reproductive outcomes including live birth rates (LBRs), 1227 women who returned for a second attempt were compared with 13,195 women undergoing their first oocyte retrieval with blastocyst culture attempted during the same study period. RESULTS: In women who had a second cycle, the median number of oocyte retrieved (11 vs 9), fertilized oocytes (7 vs 5), usable embryos (6 vs 4) and blastocysts (3 vs 1) was higher in the second cycle compared to the first cycle (All p < 0.001). Blastocyst formation rates were significantly increased from 33% in the first cycle to 50% in the second cycle across the age group (p < 0.001). However, the primary transfer LBRs were significantly lower in the second cycle than that in the initial cycle (40.82% versus 51.79%, aOR: 0.74 [0.65, 0.84]). LBRs in the second cycle were 42.26%, 42.68%, 25.49% and 16.22% in women aged < 35, 35-37, 38-40, and > 40 years. CONCLUSION: There was a notable enhancement in laboratory outcomes following the second attempt in women whose initial IVF cycles were unsuccessful. However, the uncertainty inherent in the successful implantation and the consequent progression to live birth remains a significant challenge.

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).

A Comparative Study of Causality Detection Methods in Root Cause Diagnosis: From Industrial Processes to Brain Networks.

Abstracting causal knowledge from process measurements has become an appealing topic for decades, especially for fault root cause analysis (RCA) based on signals recorded by multiple sensors in a complex system. Although many causality detection methods have been developed and applied in different fields, some research communities may have an idiosyncratic implementation of their preferred methods, with limited accessibility to the wider community. Targeting interested experimental researchers and engineers, this paper provides a comprehensive comparison of data-based causality detection methods in root cause diagnosis across two distinct domains. We provide a possible taxonomy of those methods followed by descriptions of the main motivations of those concepts. Of the two cases we investigated, one is a root cause diagnosis of plant-wide oscillations in an industrial process, while the other is the localization of the epileptogenic focus in a human brain network where the connectivity pattern is transient and even more complex. Considering the differences in various causality detection methods, we designed several sets of experiments so that for each case, a total of 11 methods could be appropriately compared under a unified and reasonable evaluation framework. In each case, these methods were implemented separately and in a standard way to infer causal interactions among multiple variables to thus establish the causal network for RCA. From the cross-domain investigation, several findings are presented along with insights into them, including an interpretative pitfall that warrants caution.

[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.

Hollow Core-Shell Bismuth Based Al-Doped Silica Materials for Powerful Co-Sequestration of Radioactive I2 and CH3 I.

Developing pure inorganic materials capable of efficiently co-removing radioactive I2 and CH3 I has always been a major challenge. Bismuth-based materials (BBMs) have garnered considerable attention due to their impressive I2 sorption capacity at high-temperature and cost-effectiveness. However, solely relying on bismuth components falls short in effectively removing CH3 I and has not been systematically studied. Herein, a series of hollow mesoporous core-shell bifunctional materials with adjustable shell thickness and Si/Al ratio by using silica-coated Bi2 O3 as a hard template and through simple alkaline-etching and CTAB-assisted surface coassembly methods (Bi@Al/SiO2 ) is successfully synthesized. By meticulously controlling the thickness of the shell layer and precisely tuning of the Si/Al ratio composition, the synthesis of BBMs capable of co-removing radioactive I2 and CH3 I for the first time, demonstrating remarkable sorption capacities of 533.1 and 421.5 mg g-1 , respectively is achieved. Both experimental and theoretical calculations indicate that the incorporation of acid sites within the shell layer is a key factor in achieving effective CH3 I sorption. This innovative structural design of sorbent enables exceptional co-removal capabilities for both I2 and CH3 I. Furthermore, the core-shell structure enhances the retention of captured iodine within the sorbents, which may further prevent potential leakage.

Laparoscopic Transduodenal Ampullectomy: How We Have Standardized the Technique (with Video).

BACKGROUND: The procedure of choice for the resection of ampullary tumors comprises transduodenal ampullectomy (TDA), endoscopic papillectomy (EP), and pancreaticoduodenectomy (PD).1 For neoplasms with low-grade dysplasia, TDA and EP have equivalent efficacies and lower morbidities than PD1. Compared with EP, also as an organ-preserving procedure, TDA could be applicable for tumors involving the pancreatic ducts or common bile ducts.2 Because TDA has a lower incidence of postoperative gastrointestinal bleeding and a higher R0 resection rate, its use could avoid the need to use multiple endoscopic procedures for larger lesions.3 Furthermore, during TDA, surgeons could convert to PD as necessary. However, TDA has rarely been performed using a minimally invasive approach that addresses the shortcomings of both the endoscopic and open surgical techniques without adding significant morbidity or compromising outcomes.2,4 Conventional laparoscopic TDA (LTDA) remains limited due to the complexity of the surgical anatomy of the ampulla and the reconstruction required compared with robot-assisted procedures.2-5 However, robot-assisted surgery is less popular and much more expensive than laparoscopic surgery. This report with a video describes the LTDA approach to standardize and simplify the surgical processes. METHODS: A 48-year-old man was admitted to the hospital with epigastric pain. He had a history of cholecystolithiasis with chronic cholecystitis. A tumor approximately 2.2 cm in diameter located in the duodenal papilla was diagnosed by an enhanced computed tomography (CT) scan. The endoscopic biopsy result indicated a villous adenoma with moderate dysplasia. Laparoscopic TDA and cholecystectomy were planned. However, if the frozen sample analysis showed adenocarcinoma, laparoscopic PD (LPD) would be applied. The patient was placed in the supine position with both legs apart. Trocars were distributed in the same manner as in the authors' previous study to facilitate conversion to LPD.6 The procedure began with kocherization and dissection of the gastrocolic ligament to explore the second and third portions of the duodenum. A figure-eight suture was made using 4-0 prolene in the seromuscular layer, and then the duodenum was retracted to the left side of the patient. A longitudinal duodenotomy was made, and the ampulla of Vater was identified. A transfixing suture was placed through the tumor. Submucosal injection of norepinephrine (1:500) was performed to divide the mucosa from the muscular planes. Ampullectomy was performed by first dissecting in the submucosal plane with a harmonic scalpel at the 6 o'clock position until the pancreatic duct was reached. A 6-Fr plastic catheter was inserted into the pancreatic duct for subsequent reconstruction. Continued dissection around the tumor identified the bile duct. Another 6-Fr plastic catheter was inserted into the bile duct. The dissection was completed in the submucosal plane, and the specimen was retrieved for frozen sectioning. After confirmation of villous adenoma with moderate dysplasia and the proximal margin without residual tumor on frozen biopsy, reconstruction was performed. The septum between the ducts was plastered, and the bile and pancreatic ducts were reconstructed on the duodenal wall with 5-0 PDS-II interrupted sutures to ensure that these ducts remained patent and connected. After reconstruction, the plastic catheter was kept in the pancreatic duct but removed from the bile duct. Then, cholecystectomy was applied. Finally, the duodenum was closed obliquely in two layers, and two drains were routinely placed. RESULTS: The operation time was 139 min, and the estimated blood loss was 50 ml. Final pathology confirmed villous adenoma with mild to moderate dysplasia. The postoperative course was uneventful, with a hospital stay of 9 days. There was no evidence of recurrence or patency of the reimplanted ducts 5 months after surgery. From February 2022 to May 2022, four cases of LTDA with the same surgical processes were managed by the authors, and all the patients recovered quickly without any postoperative complications. CONCLUSION: After standardization of the surgical processes, laparoscopic TDA was safe for highly selected patients. However, long-term follow-up is required to observe the quality of life and survival of patients.

Single-port laparoscopic pancreaticoduodenectomy.

BACKGROUND: Performing a single-port laparoscopic pancreatectomy is technically challenging. Single-port laparoscopic pancreaticoduodenectomy (SPLPD) is rarely reported in English literature. METHODS: Eighty-seven cases of laparoscopic pancreaticoduodenectomy (LPD) were performed by a single surgical team in the Department of Pancreatic Surgery, West China Hospital, Sichuan University between February 2020 and December 2020. Among these, 13 cases of LPD (group 1) were performed using a single-port device. Basing on the same inclusion and exclusion criteria, 68 cases of LPD performed using traditional 5-trocar were included as a control group (group 2). The patient's demographic characteristics, intraoperative, and postoperative variables were prospectively collected and retrospectively analyzed. RESULTS: Five men and eight women were included in the SPLPD group. The median age of these patients was 57 years. The patients who underwent SPLPD required a longer operative time (332.7 ± 38.1 min vs. 305.8 ± 64.7 min; p = 0.03) than those in the LPD group. The estimated blood loss, conversion rate, blood transfusion rate, time to oral intake, postoperative hospital stays, and perioperative complications were comparable between the two groups. The short-term oncological outcomes, such as R0 rate and lymph node harvested, were comparable between the two groups. The 90-day mortality of all patients was zero. CONCLUSIONS: SPLPD is a safe and feasible procedure for well-selected patients in an experienced minimally invasive pancreatic surgery team. SPLPD may provide several potential advantages, such as the requirement of fewer trocars, fewer abdominal complications, and reduced participation of assistants than conventional LPD.

Effect modification by developmental stage of embryos on the association between late follicular phase progesterone elevation and live birth in fresh transfers.

BACKGROUND: Late follicular phase progesterone elevation (LFPE) during ovarian stimulation is associated with reduced live birth rates (LBRs) after cleavage-stage embryo transfer. However, due to better synchronization with a stimulated endometrium, prior studies shown that LFPE had no effect on transferring embryos at blastocyst stage. The study aim to exam whether the developmental stage of embryos and serum progesterone levels on the day of human chorionic gonadotropin (hCG) administration jointly affect the odds of live birth in fresh fresh IVF/intracytoplasmic sperm injection (ICSI) cycles.  METHODS: The single-center retrospective cohort study included a total of 4,471 fresh embryo transfer cycles with 2,342 at cleavage stage versus 2,129 at blastocyst stage. Patients underwent IVF/ICSI with ovarian stimulation in gonadotropin-releasing hormone antagonist protocol. The serum progesterone level was examined both as a continuous variable and as a categorical variable by quartiles. Analysis was performed using the generalized estimating equations framework and multivariate regression models. RESULTS: LBRs were inversely associated with progesterone as a continuous variable on the day of hCG in both the cleavage-stage (crude OR 0.87, 95%CI 0.73-1.03; adjusted OR 0.80, 95% CI 0.65-0.98) and the blastocyst-stage (crude OR 0.66, 95%CI 0.56-0,78; adjusted OR 0.61, 95%CI 0.50-0.73) groups. The interaction testing was highly significant (P = 0.018) indicating an effect modifying role of stage of embryos transferred on the association of pregesterone values with the LBRs in fresh cycles. A similar pattern for a greater reduction in ORs for live birth in cycles with blastocysts transfer was also observed when progesterone was analyzed by interquartile ranges. The findings remained unchanged in subgroup analysis stratified by types of ovarian response. CONCLUSIONS: In fresh cycles, detrimental effect of late follicular phase progesterone elevation on live birth was more prominent in blastocyst-stage group compared with that in clevaged-stage group.

New measure of functional tooth loss for successful Oral ageing: a cross-sectional study.

BACKGROUND: This cross-sectional study evaluated the impacts of functional tooth loss on oral health-related quality of life (OHRQoL) among elderly people compared with the impacts of several common indicators of oral health. Additionally, the cut-off of functional tooth loss needed for a better OHRQoL was investigated to establish a new measure for successful oral ageing. METHODS: Data from people aged 65-74 were extracted from the Fourth National Oral Health Survey in Sichuan, China. Functional tooth loss was defined as both natural tooth loss and nonfunctional teeth, such as third molars, residual roots, and removable dentures. The cut-offs of tooth loss were first identified as 12, based on the previous definition of functional dentition (≥20 natural teeth except the third molars), and 14, 16, or 18 for further investigation. OHRQoL was evaluated by the standardized Geriatric Oral Health Assessment Index (sGOHAI) score. Logistic regression was performed to estimate the impacts on OHRQoL. Additionally, subgroup analyses were conducted using the stratified chi-square test to explore the effect of functional tooth loss at each position. RESULTS: The mean GOHAI score of the 744 participants was 48.25 ± 7.62. Elderly people who had lost ≤12 functional teeth had greater odds of reporting a higher sGOHAI score than those who had lost more functional teeth (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.05-2.11). No significant difference in the sGOHAI score was detected between people who had lost 13-16 functional teeth and those who had lost ≤12 functional teeth (0.61, 0.35-1.07). The loss of second premolars and first and second molars had great impacts on the sGOHAI score when ≤12 or ≤ 16 functional teeth had been lost. CONCLUSIONS: Compared with natural tooth loss, functional dentition and occluding pairs, functional tooth loss can be a better indicator of OHRQoL in the elderly population. Sixteen remaining functional teeth seem to be sufficient to maintain good OHRQoL and successful oral ageing despite that number being previously acknowledged as ≥20 teeth.

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.

Association between polymorphisms of anti-inflammatory gene alleles and periodontitis risk in a Chinese Han population.

OBJECTIVE: Cytokines that mediate the immune responses are important in the pathogenesis of periodontitis. The genetic polymorphisms of IL-10, TNFAIP3 (A20), and NF-κB1 (p105/p50) and their association with the risk of periodontitis were investigated. METHOD: Venous blood from 102 clinical periodontal healthy participants and 100 patients with periodontitis was collected to genotype the IL-10 (rs1800872), A20 (rs2230926, rs5029937, rs6927127), and NF-κB1 (rs28362491) SNP loci by Sanger technology. Univariable and multivariable logic regression and path analysis model was used to analyze the genotypes and alleles. RESULT: Single-gene mutations in the A20 (rs2230926, rs5029937, rs6927127) and IL-10 (rs1800872) genes were not associated with the risk of periodontitis. NF-κΒ1 (rs28362491) gene influenced periodontitis susceptibility by affecting CAL. The combined effect of A20 and IL-10 was related to the risk of periodontitis (ORa = 0.123-0.151). One site mutated in the A20 (rs2230926, rs5029937, rs6927127) gene or IL-10 (rs1800872) gene reduced the risk of periodontitis. CONCLUSION: Single gene polymorphisms in A20 and IL-10 genes were not associated with the risk of periodontitis. NF-κB1 gene polymorphism indirectly affects susceptibility to periodontitis. The combined effect of anti-inflammatory gene polymorphisms (A20 and IL-10) correlated with the decreased risk of periodontitis. CLINICAL RELEVANCE: This study helps to explore the potential mechanisms underlying the role of anti-inflammatory genes in the progression of periodontal disease and provides a basis for the selection and development of appropriate periodontal treatment strategies based on the genetic profile of the patient.

miR-145-3p Inhibits MuSCs Proliferation and Mitochondria Mass via Targeting MYBL1 in Jianzhou Big-Eared Goats.

Muscle growth and injury-induced regeneration are controlled by skeletal muscle satellite cells (MuSCs) through myogenesis in postnatal animals. Meanwhile, myogenesis is accompanied by mitochondrial function and enzyme activity. Nevertheless, the underlying molecular mechanisms involving non-coding RNAs including circular RNAs (circRNAs) and microRNAs (miRNAs) remain largely unsolved. Here, we explored the myogenic roles of miR-145-3p and MYBL1 on muscle development and mitochondrial mass. We noticed that overexpression of miR-145-3p inhibited MuSCs proliferation and reduced the number of viable cells. Meanwhile, deficiency of miR-145-3p caused by LNAantimiR-145-3p or an inhibitor retarded the differentiation of MuSCs. miR-145-3p altered the mitochondrial mass in MuSCs. Moreover, miR-145-3p targeted and negatively regulated the expression of CDR1as and MYBL1. The knockdown of the MYBL1 using ASO-2'MOE modification simulated the inhibitory function of miR-145-3p on cell proliferation. Additionally, MYBL1 mediated the regulation of miR-145-3p on Vexin, VCPIP1, COX1, COX2, and Pax7. These imply that CDR1as/miR-145-3p/MYBL1/COX1, COX2, VCPIP1/Vexin expression at least partly results in a reduction in mitochondrial mass and MuSCs proliferation. These novel findings confirm the importance of mitochondrial mass during myogenesis and the boosting of muscle/meat development in mammals.

The efficacy of mouthwashes on oral microorganisms and gingivitis in patients undergoing orthodontic treatment: a systematic review and meta-analysis.

BACKGROUND: Mouthwashes were convenient adjuncts to mechanical cleaning procedures. This review aimed to evaluate the efficacy of mouthwashes on oral microorganisms and gingivitis in orthodontic patients. METHODS: By April 16, 2022, multiple databases and grey literature were searched based on the PICOS strategy. Randomized controlled trials in orthodontic patients evaluating the efficacy of mouthwashes with at least one microbial parameter and/or plaque- and/or gingival inflammation-related index were included. Relevant data were extracted, and the risk of bias was evaluated using Cochrane's tool. Individual mean and standard deviation of the outcomes in mouthwashes and placebos/blank controls were pooled to estimate the weighted mean differences (WMDs) and 95% confidence intervals (95%CIs). Sensitivity analysis, and certainty of evidence were evaluated. RESULTS: Of 1684 articles, 32 studies satisfied the eligibility criteria, and nine were included for meta-analysis. Missing outcome data was the primary source of bias. Compared to blank controls, the short-term application of fluoride mouthwashes significantly reduced the colony counts of Mutans streptococci (MS), while the long-term application may not be effective. Compared to placebos or blank controls, Chlorhexidine mouthwashes significantly reduced the colony counts of multiple microorganisms in the short-term. Compared to placebos or blank controls, herbal mouthwashes showed the inhibitory effect of MS in the short-term, with some results lacking statistical significance. After meta-analysis, significant lower plaque- and gingival inflammation-related indexes were observed in the Chlorhexidine mouthwashes groups [Gingival Index: WMD = -0.45, 95%CI = -0.70 to -0.20 (placebos as control); WMD = -0.54, 95%CI = -0.96 to -0.13 (blank controls); Plaque Index: WMD = -0.70, 95%CI = -1.12 to -0.27 (blank controls)]. Significant lower gingival inflammation-related indexes were observed in the herbal mouthwashes groups [Gingival Index: WMD = -0.20, 95%CI = -0.32 to -0.09 (blank controls)]. CONCLUSIONS: The short-term application of fluoride mouthwashes may reduce the colony counts of cariogenic bacteria, but the long-term effect is not evident. Chlorhexidine may reduce the colony counts of multiple microorganisms in the short-term. Short-term application Chlorhexidine and herbal mouthwashes may effectively reduce plaque- and gingival inflammation-related indexes. However, the risk of bias, inconsistency, and imprecision in the included studies may reduce the certainty of the evidence.

Conception and pregnancy outcome after laparoscopic treatment of subtle distal fallopian tube abnormalities in infertile women: a prospective cohort study.

RESEARCH QUESTION: What are conception rates and pregnancy outcomes after laparoscopic treatment of subtle distal tubal abnormalities among infertile women, and which factors relate to natural conception? DESIGN: Prospective cohort study (n = 234) conducted in a single fertility referral centre between January 2017 and December 2018. Subtle abnormalities included fimbrial agglutination, tubal diverticula, accessory ostium, fimbrial phimosis and accessory fallopian tube. Pregnancy outcomes were followed-up annually until 36 months. RESULTS: One hundred and nine patients conceived naturally (natural conception rate 46.6%), and 59 patients conceived after IVF. Term live birth rate of the natural conception group was significantly higher than the IVF conception group (86.2% versus 71.2%, chi-squared = 5.625, P = 0.018). Preterm birth (11.9% versus 0%, P = 0.001) and multiple pregnancy rates (27.1% versus 0%, P < 0.001) of the IVF conception group were significantly higher than the natural conception group. Patient age (hazard ratio = 0.917, 95% CI 0.870 to 0.967, P = 0.001), duration of infertility (hazard ratio = 0.846, 95% CI 0.740 to 0.966, P = 0.014) and concurrent types of subtle abnormalities (hazard ratio = 0.636, 95% CI 0.416 to 0.970, P = 0.036) were factors associated with natural conception. CONCLUSIONS: Laparoscopy is an effective treatment for infertile patients with subtle abnormalities, especially for young patients with a short infertile period and at most two types of subtle abnormalities. For older women, a long infertile period and more than two types of subtle abnormalities, IVF may be more suitable after laparoscopic diagnosis.

Differential OAT methylation correlates with cell infiltration in tumor microenvironment and overall survival postradiotherapy in oral squamous cell carcinoma patient.

BACKGROUND: Given that DNA methylation and tumor microenvironment (TME) are susceptible to radiotherapy, we aimed to figure out specific differential DNA methylation to reflect oral squamous cell carcinoma (OSCC) prognosis and associated effect on TME changes postradiotherapy, performing as an efficient biomarker. MATERIALS AND METHODS: Differentially methylation analysis was performed using data from The Cancer Genome Atlas. Curves of Kaplan-Meier (K-M) survival, cumulative hazard and events, Cox proportional hazards, and linear regression model were conducted to screen and validate differential methylation genes, while multiple regression equation to analyze if ornithine aminotransferase (OAT) methylation correlates with radiotherapy. For correlation between OAT methylation and immune infiltrates, CIBERSORT and ESTIMATE algorithms were performed, following gene set enrichment analysis (GSEA) and ssGSEA analysis to evaluate biological process. RESULTS: Compared to normal tissues, only OAT in OSCC was differential significantly by K-M analysis (p = 0.0364). OAT hypermethylation was associated with increased overall survival (hazard ratio: 0.65, p = 0.0358). Radiotherapy correlated with OAT methylation (ß = -0.01, p = 0.0061); most patients with OAT hypermethylation were radiation-sensitive. Hypomethylated OAT correlated with higher cell infiltrations in TME. Neuroactive ligand-receptor interaction was most significantly related to OAT methylation (p = 9.2e-10). Sulfur metabolism was the most significantly in OAT hypermethylation group (p = 0.0041) and RIG-I-like receptor in OAT hypomethylation group (p = 0.0094). CONCLUSION: OAT methylation can serve as a predictor of OSCC prognosis postradiotherapy with potential mechanism by changing cell infiltrations in TME, but further experimental study deserves to carry out confirming the role and mechanism of OAT methylation in OSCC.

"Plane first" approach for laparoscopic radical antegrade modular pancreatosplenectomy.

BACKGROUND: Laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS) has not been widely performed due to its technical challenging. We introduce a novel approach, named "Plane first" approach, for L-RAMPS in this study. METHODS: From January 2015 to August 2021, we performed 51 cases of L-RAMPS. Patients were divided into two groups basing on the surgical approach: conventional approach (group 1) and "Plane first" approach (group 2). Data were retrospectively collected in terms of demographic characteristics, intra-operative variables, post-operative variables, and follow-up outcomes. RESULTS: The age, sex, BMI, and tumor size were comparable between two groups. Two patients in the group 1 required converting to open surgery. The patients in the group 2 required fewer operative time (210.5 ± 65.5 min vs. 252.4 ± 24.7 min, p < 0.01). They also suffered from less blood loss (136.0 ± 100.0 ml vs. 158.8 ± 137.0 ml, p = 0.15). The overall complications for patients in two groups were comparable. In terms of oncological outcomes, posterior margin was positive in two patients (10.5%) in the group 1. One patient (3.1%) in the group 2 had positive pancreatic neck margin. The number of lymph nodes harvested and overall survival between the two groups were comparable. CONCLUSION: "Plane first" approach RAMPS for patients with pancreatic adenocarcinoma in the left pancreas is safe and feasible, even in patients with PV/SMV involvement.