Multidimensional engineering of Saccharomyces cerevisiae for the efficient production of heme by exploring the cytotoxicity and tolerance of heme.

Heme has attracted considerable attention due to its indispensable biological roles and applications in healthcare and artificial foods. The development and utilization of edible microorganisms instead of animals to produce heme is the most promising method to promote the large-scale industrial production and safe application of heme. However, the cytotoxicity of heme severely restricts its efficient synthesis by microorganisms, and the cytotoxic mechanism is not fully understood. In this study, the effect of heme toxicity on Saccharomyces cerevisiae was evaluated by enhancing its synthesis using metabolic engineering. The results showed that the accumulation of heme after the disruption of heme homeostasis caused serious impairments in cell growth and metabolism, as demonstrated by significantly poor growth, mitochondrial damage, cell deformations, and chapped cell surfaces, and these features which were further associated with substantially elevated reactive oxygen species (ROS) levels within the cell (mainly H2O2 and superoxide anion radicals). To improve cellular tolerance to heme, 5 rounds of laboratory evolution were performed, increasing heme production by 7.3-fold and 4.2-fold in terms of the titer (38.9 mg/L) and specific production capacity (1.4 mg/L/OD600), respectively. Based on comparative transcriptomic analyses, 32 genes were identified as candidates that can be modified to enhance heme production by more than 20% in S. cerevisiae. The combined overexpression of 5 genes (SPS22, REE1, PHO84, HEM4 and CLB2) was shown to be an optimal method to enhance heme production. Therefore, a strain with enhanced heme tolerance and ROS quenching ability (R5-M) was developed that could generate 380.5 mg/L heme with a productivity of 4.2 mg/L/h in fed-batch fermentation, with S. cerevisiae strains being the highest producers reported to date. These findings highlight the importance of improving heme tolerance for the microbial production of heme and provide a solution for efficient heme production by engineered yeasts.

Cross-reaction mediated by distinct key amino acid combinations in the complementary-determining region (CDR) of a monoclonal antibody.

In immunology, cross-reaction between antigens and antibodies are commonly observed. Prior research has shown that various monoclonal antibodies (mAbs) can recognize a broad spectrum of epitopes related to influenza viruses. However, existing theories on cross-reactions fall short in explaining the phenomena observed. This study explored the interaction characteristics of H1-74 mAb with three peptides: two natural peptides, LVLWGIHHP and LPFQNI, derived from the hemagglutinin (HA) antigen of the H1N1 influenza virus, and one synthetic peptide, WPFQNY. Our findings indicate that the complementarity-determining region (CDR) of H1-74 mAb comprised five antigen-binding sites, containing eight key amino acid residues from the light chain variable region and 16 from the heavy chain variable region. These critical residues formed distinct hydrophobic or hydrophilic clusters and functional groups within the binding sites, facilitating interaction with antigen epitopes through hydrogen bonding, salt bridge formation, and π-π stacking. The study revealed that the formation of the antibody molecule led to the creation of binding groups and small units in the CDR, allowing the antibody to attach to a variety of antigen epitopes through diverse combinations of these small units and functional groups. This unique ability of the antibody to bind with antigen epitopes provides a new molecular basis for explaining the phenomenon of antibody cross-reaction.

Focused ultrasound versus the loop electrosurgical excision procedure to treat women with cervical high-grade squamous intraepithelial lesions under 40: a retrospective study.

BACKGROUND: This study aimed to compare the efficacy of focused ultrasound (FUS) and the loop electrosurgical excision procedure (LEEP) for the treatment of cervical high-grade squamous intraepithelial lesions (HSILs) among women of reproductive age. METHODS: Case records of patients aged < 40 years who were treated for cervical HSILs using either FUS or LEEP from September 1, 2020 to May 31, 2022 were retrospectively reviewed. Patients were followed up for cure, recurrence, human papillomavirus (HPV) clearance, and complications within 1 year of treatment. Odds ratios and 95% confidence intervals were determined using univariate and multivariate logistic regression models to analyze the association between disease evidence or HPV clearance and treatment modalities or other covariates. RESULTS: Of the 1,054 women who underwent FUS or LEEP, 225 met our selection criteria. Among the selected women, 101 and 124 received FUS and LEEP, respectively. There was no significant difference between the FUS and LEEP groups in the cure rate during the 3-6 months of follow-up (89.11% vs. 94.35%, P = 0.085) and recurrence rate during the 6-12 months follow-up (2.22% vs. 1.71%, P = 0.790). Both groups exhibited enhanced cumulative HPV clearance rates; however, the rates were not significantly different between the FUS and LEEP groups (74.23% vs. 82.79%, P = 0.122 during the 3-6 months follow-up; 84.95% vs. 89.17%, P = 0.359 during the 6-12 months follow-up). Furthermore, the incidence of complications caused by the FUS and LEEP techniques was comparable (5.0% vs. 5.6%, P = 0.818). CONCLUSIONS: We found that FUS and LEEP have similar efficacy, safety, and reliability in treating women (aged < 40 years) with HSILs.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Association between negative life events through mental health and non-suicidal self-injury with young adults: evidence for sex moderate correlation.

BACKGROUND: Non-suicidal self-injury (NSSI) has exhibited an increasing trend in recent years and is now globally recognized as a major public health problem among adolescents and young adults. Negative life events (NLEs) are positively associated with NSSI. We sought to explore (1) whether sex plays a role in the risk of NLEs leading to NSSI and (2) the role played by mental health (MH). METHODS: We adopted a multi-stage cluster sampling method to select college students across four grades from May to June 2022. Generalized linear models were used to evaluate the relationships between NLEs, sex, MH and NSSI, presented as incidence-rate ratios (RRs) with 95% confidence intervals (CIs). We examined the complex relationship between these variables using the PROCESS method for moderation analysis. RESULTS: Following the exclusion of data that did not meet the study requirements, data from 3,578 students (mean age: 20.53 [± 1.65] years) were included. Poisson regression results indicate that high-level NLEs (RR = 0.110, 95%CI: 0.047-0.173) are associated with increased NSSI. Furthermore, interaction effects were observed among sex, NLEs and NSSI. MH and sex moderated the relationship between NLEs and NSSI. CONCLUSION: Identifying risk factors for NSSI is also important when exploring the interaction between NLEs and MH given the potential for NSSI to significantly increase the risk of later psychopathological symptoms and substance abuse problems. In addition, the significance of sex differences in risk factors for NSSI should be determined. This study evaluated how the impact of NLEs on NSSI can be reduced among adolescents from multiple perspectives.

Applications of magnetic solid-phase extraction in the sample preparation of natural product analysis (2020-2023).

Sample preparation, including extraction, separation, and purification, is a vital process for natural product analysis. As an attractive sample pretreatment method, magnetic solid-phase extraction (MSPE) has gained plenty of attention, mainly due to its simpler operation, less consumption of organic solvents, and shorter processing time than traditional SPE. This updated review is devoted to summarizing the applications of MSPE based on different magnetic nanomaterials in the analysis of various natural products in complex matrixes, such as biological samples, plants, and Chinese herbal preparations in the past four years (2020-2023). The preparation and fabrication of different materials are briefly introduced. Furthermore, the extraction mechanism and interaction forces between adsorbent and analytes are elaborated, and the advantages and disadvantages of different adsorbents coupled with various analytical methods for MSPE of different natural products are summarized. Moreover, the future trends and opportunities for MSPE in the natural product analysis are discussed. It is expected that this work can provide updated information for future research on the applications of MSPE in such fields.

Implementation of social needs screening for minoritized patients newly diagnosed with breast cancer: a mixed methods evaluation in a pragmatic patient navigation trial.

BACKGROUND: Social needs inhibit receipt of timely medical care. Social needs screening is a vital part of comprehensive cancer care, and patient navigators are well-positioned to screen for and address social needs. This mixed methods project describes social needs screening implementation in a prospective pragmatic patient navigation intervention trial for minoritized women newly diagnosed with breast cancer. METHODS: Translating Research Into Practice (TRIP) was conducted at five cancer care sites in Boston, MA from 2018 to 2022. The patient navigation intervention protocol included completion of a social needs screening survey covering 9 domains (e.g., food, transportation) within 90 days of intake. We estimated the proportion of patients who received a social needs screening within 90 days of navigation intake. A multivariable log binomial regression model estimated the adjusted rate ratios (aRR) and 95% confidence intervals (CI) of patient socio-demographic characteristics and screening delivery. Key informant interviews with navigators (n = 8) and patients (n = 21) assessed screening acceptability and factors that facilitate and impede implementation. Using a convergent, parallel mixed methods approach, findings from each data source were integrated to interpret study results. RESULTS: Patients' (n = 588) mean age was 59 (SD = 13); 45% were non-Hispanic Black and 27% were Hispanic. Sixty-nine percent of patients in the navigators' caseloads received social needs screening. Patients of non-Hispanic Black race/ethnicity (aRR = 1.25; 95% CI = 1.06-1.48) and those with Medicare insurance (aRR = 1.13; 95% CI = 1.04-1.23) were more likely to be screened. Screening was universally acceptable to navigators and generally acceptable to patients. Systems-based supports for improving implementation were identified. CONCLUSIONS: Social needs screening was acceptable, yet with modest implementation. Continued systems-based efforts to integrate social needs screening in medical care are needed.

Co-augmentation of a transport gene mfsT1 in Mycolicibacterium neoaurum with genome engineering to enhance ergothioneine production.

Ergothioneine (EGT) is a rare thiohistidine derivative with exceptional antioxidant properties. The blood level of EGT is considered highly reliable predictors for cardiovascular diseases and mortality, yet animals lack the ability to synthesize this compound. Free plasmids have been previously used to overexpress genes involved in the EGT biosynthetic pathway of Mycolicibacterium neoaurum. Here, we tentatively introduced a putative transporter gene mfsT1 into high-copy plasmids and sharply increased the ratio of extracellular EGT concentration from 18.7% to 44.9%. Subsequently, an additional copy of egtABCDE, hisG, and mfsT1 was inserted into the genome with a site-specific genomic integration tool of M. neoaurum, leading a 2.7 times increase in EGT production. Co-enhancing the S-adenosyl-L-methionine regeneration pathway, or alternatively, the integration of three copies of egtABCDE, hisG and mfsT1 into the genome further increased the total EGT yield by 16.1% (64.6 mg/L) and 21.7% (67.7 mg/L), respectively. After 168-h cultivation, the highest titer reached 85.9 mg/L in the latter strain with three inserted copies. This study provided a solid foundation for genome engineering to increase the production of EGT in M. neoaurum.

Applications of Nanozymes in Chiral-Molecule Recognition through Electrochemical and Ultraviolet-Visible Analysis.

Chiral molecules have similar physicochemical properties, which are different in terms of physiological activities and toxicities, rendering their differentiation and recognition highly significant. Nanozymes, which are nanomaterials with inherent enzyme-like activities, have garnered significant interest owing to their high cost-effectiveness, enhanced stability, and straightforward synthesis. However, constructing nanozymes with high activity and enantioselectivity remains a significant challenge. This review briefly introduces the synthesis methods of chiral nanozymes and systematically summarizes the latest research progress in enantioselective recognition of chiral molecules based on electrochemical methods and ultraviolet-visible absorption spectroscopy. Moreover, the challenges and development trends in developing enantioselective nanozymes are discussed. It is expected that this review will provide new ideas for the design of multifunctional chiral nanozymes and broaden the application field of nanozymes.

Detection of Arsenic(V) by Fluorescence Sensing Based on Chlorin e6-Copper Ion.

The high toxicity of arsenic (As) can cause irreversible harm to the environment and human health. In this study, the chlorin e6 (Ce6), which emits fluorescence in the infrared region, was introduced as the luminescence center, and the addition of copper ion (Cu2+) and As(V) provoked a regular change in fluorescence at 652 nm, whereas that of As(III) was 665 nm, which was used to optionally detect Cu2+, arsenic (As(III), and As(V)). The limit of detection (LOD) values were 0.212 µM, 0.089 ppm, and 1.375 ppb for Cu2+, As(III), and As(V), respectively. The developed method can be used to determine Cu2+ and arsenic in water and soil with good sensitivity and selectivity. The 1:1 stoichiometry of Ce6 with Cu2+ was obtained from the Job plot that was developed from UV-visible spectra. The binding constants for Cu2+ and As(V) were established to be 1.248 × 105 M-1 and 2.35 × 1012 M-2, respectively, using B-H (Benesi-Hildebrand) plots. Fluorescence lifetimes, B-H plots, FT-IR, and 1H-NMR were used to postulate the mechanism of Cu2+ fluorescence quenching and As(V) fluorescence restoration and the interactions of the two ions with the Ce6 molecule.

[Gene cloning and functional analysis of an iridoid oxidase gene in Rehmannia glutinosa].

Rehmannia glutinosa is one of the commonly used Chinese herbal medicines, which has activities of heat-clearing,blood-cooling, Yin-nourishing, and body fluid-promoting. Iridoid glycosides are the main bioactive in R. glutinosa. Iridoid oxidase is a key rate-limiting enzyme in the biosynthetic pathway of iridoid glycosides. In this study, an iridoid oxidase gene Rg IO was screened based on the transcriptome data, followed by bioinformatics analysis, expression characteristic detection, and subcellular localization analysis. The results show that the coding region of Rg IO is 1 536 bp, with 511 amino acids encoded, and the molecular weight is about 58 258. 01. The protein sequence of Rg IO contains the conserved domains and motifs of cytochrome P450 oxidases. Rg IO has the highest sequence identities with its ortholog proteins in Striga asiatica, Striga hermonthica, and Centranthera grandiflora and has good sequence identities(77. 28%) with Catharanthus roseus Cr IO. Rg IO shows specific expression in the leaf of R. glutinosa. In response to MeJA induction, the expression of MeJA in leaves and roots after treatment increases by 3. 15 and 1. 3 times at 3 h and 6 h,respectively. The result of subcellular localization shows that Rg IO is distributed in the endoplasmic reticulum. Agrobacterium-mediated transient expression of Rg IO gene in leaves of R. glutinosa makes the content of catalpol increase by 0. 82 times compared with the transient expression of the empty vector. This study provides a key target gene for the molecular regulation and biosynthesis of catalpol in R. glutinosa and lays a foundation for revealing the complete biosynthetic pathway of catalpol.

Biomechanical behaviour of a novel bone cement screw in the minimally invasive treatment of Kummell's disease: a finite element study.

OBJECTIVE: To investigate and evaluate the biomechanical behaviour of a novel bone cement screw in the minimally invasive treatment of Kummell's disease (KD) by finite element (FE) analysis. METHODS: A validated finite element model of healthy adult thoracolumbar vertebrae T12-L2 was given the osteoporotic material properties and the part of the middle bone tissue of the L1 vertebral body was removed to make it wedge-shaped. Based on these, FE model of KD was established. The FE model of KD was repaired and treated with three options: pure percutaneous vertebroplasty (Model A), novel unilateral cement screw placement (Model B), novel bilateral cement screw placement (Model C). Range of motion (ROM), maximum Von-Mises stress of T12 inferior endplate and bone cement, relative displacement of bone cement, and stress distribution of bone cement screws of three postoperative models and intact model in flexion and extension, as well as lateral bending and rotation were analyzed and compared. RESULTS: The relative displacements of bone cement of Model B and C were similar in all actions studied, and both were smaller than that of Model A. The minimum value of relative displacement of bone cement is 0.0733 mm in the right axial rotation of Model B. The maximum Von-Mises stress in T12 lower endplate and bone cement was in Model C. The maximum Von-Mises stress of bone cement screws in Model C was less than that in Model B, and it was the most substantial in right axial rotation, which is 34%. There was no substantial difference in ROM of the three models. CONCLUSION: The novel bone cement screw can effectively reduce the relative displacement of bone cement by improving the stability of local cement. Among them, novel unilateral cement screw placement can obtain better fixation effect, and the impact on the biomechanical environment of vertebral body is less than that of novel bilateral cement screw placement, which provides a reference for minimally invasive treatment of KD in clinical practice.

Colorimetric Sensors: Methods and Applications.

Colorimetric sensors have attracted considerable attention in many sensing applications because of their specificity, high sensitivity, cost-effectiveness, ease of use, rapid analysis, simplicity of operation, and clear visibility to the naked eye [...].

[Effect and mechanism of Zuogui Pills on neural function recovery in ischemic stroke mice based on OPN/IGF-1/mTOR].

To explore the effect and mechanism of Zuogui Pills in promoting neural tissue recovery and functional recovery in mice with ischemic stroke. Male C57BL/6J mice were randomly divided into a sham group, a model group, and low-, medium, and high-dose Zuogui Pills groups(3.5, 7, and 14 g·kg~(-1)), with 15 mice in each group. The ischemic stroke model was established using photochemical embolization. Stiker remove and irregular ladder walking behavioral tests were conducted before modeling and on days 7, 14, 21, and 28 after medication. Triphenyl tetrazolium chloride(TTC) staining was performed on day 3 after modeling, and T2-weighted imaging(T2WI) and diffusion-weighted imaging(DWI) were performed on day 28 after medication to evaluate the extent of brain injury. Hematoxylin-eosin(HE) staining was performed to observe the histology of the cerebral cortex. Axonal marker proteins myelin basic protein(MBP), growth-associated protein 43(GAP43), mammalian target of rapamycin(mTOR), and its downstream phosphorylated s6 ribosomal protein(p-S6), as well as mechanism-related proteins osteopontin(OPN) and insulin-like growth factor 1(IGF-1), were detected using immunofluorescence and Western blot. Zuogui Pills had a certain restorative effect on the neural function impairment caused by ischemic stroke in mice. TTC staining showed white infarct foci in the sensory-motor cortex area, and T2WI imaging revealed cystic necrosis in the sensory-motor cortex area. The Zuogui Pills groups showed less brain tissue damage, fewer scars, and more capillaries. The number of neuronal axons in those groups was higher than that in the model group, and neuronal activity was stronger. The expression of GAP43, OPN, IGF-1, and mTOR proteins in the Zuogui Pills groups was higher than that in the model group. In summary, Zuogui Pills can promote the recovery of neural function and axonal growth in mice with ischemic stroke, and its mechanism may be related to the activation of the OPN/IGF-1/mTOR signaling pathway.

Iris Cerclage To Treat Persistent Mydriasis Following Acute Angle Closure Glaucoma Improves Visual Quality.

PRCIS: We developed a modified iris cerclage technique that improves best corrected visual acuity, pupillary parameters, self-assessed photophobia, and visual function index-14 questionnaire scores in patients with acute primary angle closure and permanent mydriasis after cataract surgery. PURPOSE: To evaluate the efficacy of a modified iris cerclage technique in patients with acute primary angle closure (PAC) and permanent mydriasis after cataract surgery. PATIENTS AND METHODS: 12 eyes of 12 patients with acute PAC and permanent mydriasis at more than 3 months after phacoemulsification combined with intraocular lens (IOL) implantation underwent modified iris cerclage. Best corrected visual acuity (BCVA), intraocular pressure (IOP), pupil diameter, and visual function index-14 (VF-14) questionnaire and self-assessed photophobia scores before surgery and at 1 week, 1 month, and 3 months postoperatively were compared. Further, the postoperative pupil position and morphology and complications were evaluated. RESULTS: BCVA improved from 0.48±0.23 preoperatively to 0.28±0.15, 0.27±0.15, and 0.26±0.14 at 1 week, 1 month, and 3 months postoperatively, respectively (P=0.008). No significant difference was observed between the preoperative and postoperative IOP (P=0.974). Pupil diameter improved from 6.34±0.51 mm preoperatively to 3.59±0.33, 3.59±0.34, and 3.58±0.32 mm at 1 week, 1 month, and 3 months postoperatively, respectively (P<0.001). Self-assessed photophobia scores improved from 3.33±0.78 preoperatively to 0.83±0.72, 0.51±0.15, and 0.45±0.14 at 1 week, 1 month, and 3 months postoperatively, respectively (P<0.001). VF-14 scores improved from 47.6±6.1 points preoperatively to 67.9±6.2, 72.1±6.1, and 73.5±6.0 points at 1 week, 1 month, and 3 months postoperatively, respectively (P<0.001). Postoperatively, all pupils were centered and round. No postoperative complications, such as iris-suture slippage, iridodialysis, or exposure of the IOL's optical zone edge, were observed. CONCLUSION: Modified iris cerclage creates a centered, precisely sized, round pupil. It improves visual quality in patients with acute PAC and permanent mydriasis after cataract surgery.

Azadirachtin Induces Fat Body Apoptosis by Suppressing Caspase-8 in the Fall Armyworm, Spodoptera frugiperda.

Azadirachtin is a widely used botanical pesticide for agricultural pest control worldwide. However, the molecular mechanisms of azadirachtin in insects are not fully understood. In this study, histological analysis and RNA sequencing were conducted to investigate the impact of azadirachtin on the larval development of Spodoptera frugiperda. Under azadirachtin exposure, the development was completely inhibited, and the major internal tissues, fat body, and midgut were strongly damaged under histological analysis. Differential gene expression analysis demonstrated that nutrient absorption and detoxification metabolism-related genes are differentially expressed. Interestingly, the expression of the apoptosis-related gene, caspase-8, was significantly inhibited under exposure to azadirachtin. In addition, after knocking down the expression of the caspase-8 gene, the fat body displayed a similar apoptotic phenotype as azadirachtin treatment; the distribution of chromatin and lipid droplets was uneven in the fat body cells. Thus, the results in this study demonstrated that exposure to azadirachtin rapidly activates apoptosis, resulting in innate tissue disruption, ultimately arresting larval development in S. frugiperda.

Narrative review of magnetic resonance imaging in quantifying liver iron load.

Objective: To summarize the research progress of magnetic resonance imaging (MRI) in quantifying liver iron load. Methods: To summarize the current status and progress of MRI technology in the quantitative study of liver iron load through reviewing the relevant literature at home and abroad. Results: Different MRI sequence examination techniques have formed a series of non-invasive methods for the examination of liver iron load. These techniques have important clinical significance in the imaging diagnosis of liver iron load. So far, the main MRI methods used to assess liver iron load are: signal intensity measurement method (signal intensity, SI) [signal intensity ratio (SIR) and difference in in-phase and out-of-phase signal intensity], T2/R2 measurement (such as FerriScan technique), ultra-short echo time (UTE) imaging technique, and susceptibility weighted imaging (including conventional susceptibility weighted imaging) (SWI), quantitative susceptibility mapping (QSM), T2*/R2* measurement, Dixon and its derivative techniques. Conclusion: MRI has become the first choice for the non-invasive examination of liver iron overload, and it is helpful to improve the early detection of liver injury, liver fibrosis, liver cirrhosis and liver cancer caused by liver iron overload.

Clinical application of ERCP concurrent laparoscopic cholecystectomy in the treatment of cholecystolithiasis complicated with extrahepatic bile duct stones.

Objective: To compare the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration and lithotomy (LCBDE) in the treatment of cholecystolithiasis combined with bile duct stones. Methods: From September 2018 to January 2022, 195 patients with cholecystolithiasis complicated with extrahepatic bile duct stones from Department of Department of General Surgery, Shanghai Jiading Central Hospital met the inclusion criteria, including 60 cases in the LC group and 86 cases in the LCBDE group. The general condition, operation success rate, complications and residual stone rate of the two groups were retrospectively analyzed. Results: In the simultaneous operation group, 58 patients successfully performed ERCP, and the indwelling rate of the abdominal drainage tube (41.7 % vs. 95.3 %) was significantly better than that in the LCBDE group. There was no significant difference in the conversion rate to open surgery, operation time, and intraoperative blood loss between the two groups. In the simultaneous surgery group, 4 patients (6.7 %) developed pancreatitis after ERCP, which was cured by conservative treatment. The pain score at 6 h after operation was significantly lower than that in the LCBDE group (3.9 ± 1.6 vs 6.5 ± 2.4). There were no significant differences in biliary leakage (1.7 % vs. 4.7 %), postoperative cholangitis (5.0 % vs. 5.8 %), incision infection (3.3 % vs. 3.5 %), and bile duct stone residue rate (5.0 % vs 3.5 %) between the two groups. There was no severe pancreatitis, second operation or death. The duration of hospital stay was shortened in the concurrent operation group (5.1 ± 2.3d vs 7.9 ± 3.7d), and the operation cost was significantly higher than that in the LCBDE group (48839.9 ± 8549.5 vs 34635.9 ± 5893.7 yuan). Conclusion: ERCP combined with LC and LCBDE are both safe and effective methods for the treatment of cholecystolithiasis combined with extrahepatic bile duct stones. The simultaneous operation group has certain advantages in patient comfort and rapid rehabilitation, which can be popularized in qualified units.

High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer.

BACKGROUND: Patatin like phospholipase domain containing 8 (PNPLA8) has been shown to play a significant role in various cancer entities. Previous studies have focused on its roles as an antioxidant and in lipid peroxidation. However, the role of PNPLA8 in colorectal cancer (CRC) progression is unclear. AIM: To explore the prognostic effects of PNPLA8 expression in CRC. METHODS: A retrospective cohort containing 751 consecutive CRC patients was enrolled. PNPLA8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive scores. CRC patients were divided into high and low PNPLA8 expression groups based on the cut-off values, which were calculated by X-tile software. The prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression analysis. The overall survival (OS) rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank test. RESULTS: PNPLA8 expression was significantly associated with distant metastases in our cohort (P = 0.048). CRC patients with high PNPLA8 expression indicated poor OS (median OS = 35.3, P = 0.005). CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter OS. For patients with left-sided colon and rectal cancer, the survival curves of two PNPLA8-expression groups showed statistically significant differences. Multivariate analysis also confirmed that high PNPLA8 expression was an independent prognostic factor for overall survival (hazard ratio HR = 1.328, 95%CI: 1.016-1.734, P = 0.038). CONCLUSION: PNPLA8 is a novel independent prognostic factor for CRC. These findings suggest that PNPLA8 is a potential target in clinical CRC management.