Immune checkpoints include a series of receptor-ligand pairs that play a key role in the proliferation, activation, and immune regulatory responses of immune cells. Although immune checkpoint inhibitors (ICIs), such as programmed death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have achieved good therapeutic effects in clinical practice, some patients still experience ineffective treatment and immune resistance. A large amount of evidence has shown that immune checkpoint proteins are related to cell metabolism during immune regulation. On the one hand, immune checkpoints connect to alter the metabolic reprogramming of tumor cells to compete for nutrients required by immune cells. On the other hand, immune checkpoints regulate the metabolic pathways of immune cells, such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) to affect the activation of immune cells. Based on a review of the literature, this article reviews the mechanisms by which PD-1, CTLA-4, T cell immunoreceptor with Ig and ITIM domains (TIGIT), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cluster of differentiation 47 (CD47), and indoleamine 2,3-dioxygenase 1 (IDO1) regulate cell metabolic reprogramming, and looks forward to whether targeting the ligand-receptor pairs of immune checkpoints in a "dual regulation" manner and inhibiting metabolic pathways can effectively solve the problem of tumor immune resistance.
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Humans ; Neoplasms/genetics* ; Metabolic Networks and Pathways/immunology* ; Animals ; Immune Checkpoint Inhibitors/pharmacology*

OBJECTIVE: To investigate the potential mechanisms of sepsis pathogenesis in intensive care unit (ICU), with a specific focus on the role of skin microbiota, and to evaluate the causal relationships between skin microbiota and ICU sepsis using Mendelian randomization (MR). METHODS: A two-sample MR analysis was performed using skin microbiota genome-wide association study (GWAS) summary data from German population cohorts as exposures, combined with ICU sepsis susceptibility and 28-day mortality GWAS summary data from the IEU OpenGWAS database as outcomes. The primary causal effect estimates were generated using the inverse variance weighted (IVW) method, supplemented by validation through MR-Egger and weighted median approaches. Heterogeneity and pleiotropy tests, along with sensitivity analyses, were conducted to evaluate the robustness of the results. RESULTS: Regarding risk of ICU sepsis, IVW analysis showed that order Pseudomonadales [odds ratio (OR) = 0.93, 95% confidence interval (95%CI) was 0.88-0.98], family Flavobacteriaceae (OR = 0.93, 95%CI was 0.90-0.96), and genus Acinetobacter (OR = 0.96, 95%CI was 0.93-0.99) were significantly negatively correlated with the risk of ICU sepsis (all P < 0.05). There was a significant positive correlation between the risk of ICU sepsis and the presence of β-Proteobacteria (OR = 1.05, 95%CI was 1.00-1.11) and Actinobacteria (OR = 1.05, 95%CI was 1.00-1.11), both P < 0.05. Regarding 28-day mortality of ICU sepsis, IVW analysis showed that phylum Bacteroidetes (OR = 0.92, 95%CI was 0.86-0.99), family Streptococcaceae (OR = 0.92, 95%CI was 0.85-0.98), family Flavobacteriaceae (OR = 0.90, 95%CI was 0.83-0.97), genus Streptococcus (OR = 0.92, 95%CI was 0.86-0.99), ASV016 [Enhydrobacter] (OR = 0.92, 95%CI was 0.87-0.98), and ASV042 [Acinetobacter] (OR = 0.92, 95%CI was 0.88-0.97) were significantly negatively correlated with the 28-day mortality of ICU sepsis (all P < 0.05); family Moraxellaceae (OR = 1.09, 95%CI was 1.00-1.18) and ASV008 [Staphylococcus] (OR = 1.08, 95%CI was 1.03-1.14) was significantly positively correlated with the 28-day mortality of ICU sepsis (both P < 0.05). Sensitivity analysis and MR-PRESSO showed no heterogeneity, pleiotropy, or horizontal pleiotropy between skin microbiota and ICU sepsis risk and 28-day mortality rate. Analysis of confounding factors showed that single nucleotide polymorphisms (SNPs) associated with relevant skin bacteria could independently and causally affect the risk of ICU sepsis or ICU sepsis related mortality rate, independent of other confounding factors. The Steiger test results indicated that the established causal relationship was not due to reverse causality. CONCLUSIONS Skin microbiota composition may influence both sepsis susceptibility and 28-day mortality in ICU settings. Family Flavobacteriaceae demonstrated protective effects against sepsis onset and mortality. These findings provide new perspectives for early detection and management strategies.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Mendelian Randomization Analysis ; Microbiota ; Skin/microbiology* ; Genome-Wide Association Study ; Risk Factors ; Skin Microbiome

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective:To investigate the clinical effect of Dynamic neutralization system applied to the treatment of lumbar degenerative diseases with fatty infiltration of multifidus muscle.Methods:From Jan 2015 to Dec 2017, a total of 53 patients of lumbar degenerative diseases with multifidus fatty infiltration treated by Dynesys in our hospital were analyzed, included 21 males and 32 females, aged 66.2±7.4 (range 48-81) years. There were lumbar spinal stenosis in 37 casesand lumbar disc herniationin 16 cases; the index level included L 2-S 1 in 3 cases, L 3-S 1 in 13 cases, L 2-L 5 in 5 cases, L 4-S 1 in 17 cases, and L 3-L 5 in 15 cases. The pedicle screws were inserted at the point of intersection of the outer edge of superior articular process and the midline of transverse process. After discectomy of herniated disc and hyperplastic ligamentum flavum, the distance between the upper and lower pedicle screws was measured and then the spacer of the corresponding length was cut out. Finally, the spacer was placed and fixed between the upper and lower pedicle screws by the elastic rope. The degree of multifidus fat infiltration, lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slop (SS), range of motion (ROM), intervertebral height (IH), Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), the MOS 36-item short-form health survey (SF-36) and visual analog scale (VAS) were evaluated postoperatively. Results:The operation was performed successfully in all the patients. The operation duration was 173.5±64.7 (range 125-240) min. Intraoperative blood loss was 469.5±118.2 (range 380-620) ml. The patients were followed up for 47.9±6.7 (range 38-62) months averagely. At the last follow-up, the degree of fatty infiltration of the multifidus muscle showed no further progress by MR scan. There was no significant difference in ROM and IH at different time points preoperativelyand postoperatively. The LL recovered from 37.6°±8.8° to 43.2°±9.1°, the PT decreased from 24.7°±9.3° to 20.5°±5.1°, and the SS increased from 22.1°±7.7°to 26.3°±8.0°. The JOA score increased from preoperative 6.4±1.2 to 20.6±2.8, ODI decreased from preoperative 50.6%±11.3% to 13.0%±3.4%, SF-36 increased from preoperative 81.5±3.6 to 95.5±4.2, and the VAS decreased from preoperative 4.2±1.0 to 1.1±0.6. One patient experienced loosening and displacement on the left side pedicle screw of the L2 vertebral body 3.5 years after operation, and herclinical symptom improved significantly after conservative treatment.Conclusion:Dynesysis is safe and effective for the treatment of lumbar degenerative diseases with fatty infiltration of multifidus muscle, and it can restore the complete structure and function of tension band at lower back and prevent the progress of multifidus muscle fat infiltration combined with postoperative rehabilitation training.

Objective:To investigate the clinical value of neuron specific enolase (NSE) and bispectral index (BIS ) in predicting the neurological prognosis in patients with severe intracerebral hemorrhage.Methods:Patients with severe intracerebral hemorrhage admitted to the ICU of Xiaolan Hospital of Southern Medical University from January 2019 to December 2020 were selected, and serum NSE detection and BIS monitoring were performed at an early stage. According to the Glasgow outcome scale (GOS) at 90 days after intracerebral hemorrhage, the patients were divided into the good neurologic prognosis group (GOS 4-5) and poor neurologic prognosis group (GOS 1-3). The levels of NSE and BIS between the two groups were compared. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive value of NSE, BIS and their combination in predicting neurological prognosis.Results:A total of 126 patients with severe intracerebral hemorrhage were enrolled in this study, and 32 patients (25.4%) had poor neurological prognosis. The level of NSC in the poor neurological prognosis group was significantly higher than that in the good neurologic prognosis group [28 (13.7, 50.4) ng/mL vs. 13.5 (9.6, 18.5) ng/mL, P < 0.05], while the BIS level was significantly lower than that in the good neurologic prognosis group [32 (25.2, 45) vs. 55 (48, 62.2), P <0.05]. For detection of poor neurologic outcome in patients with severe intracerebral hemorrhage, NSE and BIS yielded the AUC values of 0.768 (0.685, 0.839) and 0.866 (0.793, 0.920), respectively, with cut-off values of 21.7 ng/mL and 47, respectively. The combination of NSE and BIS yielded a remarkably higher AUC value of 0.927 (0.867, 0.966) for predicting poor neurologic outcome than each index alone ( P<0.05). Conclusions:Early monitoring of NSE and BIS can effectively predict the neurological prognosis of patients with severe intracerebral hemorrhage, and the combination of NSE and BIS can further improve the prediction efficiency.

Objective To analyze the safety of laparoscopic splenectomy for traumatic splenic rupture.Methods The clinical data of 62 patients with traumatic splenic rupture treated by laparoscopic splenectomy in our hospital from Jan 2013 to Jan 2018 were retrospectively analyzed.Results All 62 patients successfully underwent laparoscopic surgery except for 1 case who was converted to open surgery.One case suffered from postoperative bleeding.There was no infection,serious pancreatic leakage and other major complications.The total amount of intraoperative bleeding was 1 600 ml on average,the average operation time was 135 min,the average splenectomy time was 55 min,and the average hospital stay was 12.5 d.Conclusion Laparoscopic splenectomy is a safe and reliable minimally invasive operation for traumatic splenic rupture.

Objective To analyze CT findings in adhesive intestinal obstruction caused by different adhesion pattern.Methods Clinical data of 83 adhesive intestinal obstruction cases proved by laparotomy were reviewed.Before surgery two experienced abdominal radiologists randomly double blindly inspected and evaluated the CT findings,as to whether there was intestinal obstruction,the severity of obstruction,the site of obstruction,the adhesion type of obstruction and the diagnosis of strangulated intestinal obstruction,the consensuses were accomplished by discussion.Results The accuracy of diagnosis was 100％ for the existence of obstruction,the severity of obstruction and the site of obstruction.There were intra-abdominal hernia caused by intestinal adhesion (44 cases),a cluster of loop (12 cases),bowel twisted angle (8 cases),the intestine and abdominal adhesions (6 cases),intestinal adhesion contracture stenosis (5 cases),adhesive band compression (4 cases),intestinal volvulus caused by adhesion (1 case).The accuracy,sensitivity,specificity,positive predictive value and negative predictive value of CT in diagnosing strangulated intestinal obstruction were 78％,47％,100％,100％,73％,respectively.Conclusion CT can clearly diagnose different adhesion pattern leading to ileus and ensuing strangulation.

Objective To investigate the correlation between serum level of insulin growth factor 1 (IGF-1) and the degree of liver fibrosis in patients with chronic hepatitis C (CHC) complicated to type 2 diabetes mellitus (T2DM). Methods The cases were divided into CHC with T2DM (39 cases), CHC (96 cases), T2DM (60 cases), and healthy control (60 cases) groups. Their human data were collected and the fasting blood glucose, insulin and insulin-like growth factor-1 levels were detected, and the insulin resistance index ( HOMA-IR) wwer calculated. The serum levels of alanine transaminase ( ALT) , aspartate transaminase ( AST) , hepatitis C virus ( HCV) RNA load and HCV genotypes were detected simultaneously in patients with hepatitis C, and liver stiffness were measured ( LSM) by transient elastography ( TE) and aspartate aminotransferase-to-platelet ratio index ( APRI) score was performed. Results ⑴ There was no significant difference between CHC with T2DM group and CHC group in diabetes family history(P>0. 05), but two groups were significantly lower than that of T2DM group (P<0. 05). ⑵The levels of fasting insu-lin (FI) and HOMA-IR in CHC with T2DM group and T2DM group were significantly higher than those in the other two groups (P<0. 05), while the levels of IGF-1 in two groups were significantly lower than those in the CHC group, and were more lower than the control group (P<0. 05). ⑶Compared the serum ALT, AST and HCV RNA load between CHC with T2DM group and CHC group, there had no significant differ-ence (P>0. 05);however, the proportion of 1b genotype, LSM and APRI score of CHC with T2DM group were significantly higher than those in CHC group(P<0. 05). ⑷ The level of serum IGF-1 was negatively correlated with HOMA-IR, LSM and APRI in CHC with T2DM group (r= -0. 71, -0. 75, -0. 69, P<0. 01). Conclusions The degree of hepatic fibrosis and the damage of IGF-1 synthesis in CHC patients with T2DM were significantly higher than those in non T2DM patients, which might be related to the insulin resistance caused by 1b genotype HCV infection.

Objective:To invest the risk factors associated with delayed hemorrhage after pancreaticoduodenectomy occurred.Methods:A retrospective analysis was performed from January 2012 to June 2015 Shengjing hospital 511 cases of patients who accepted pancreaticoduodenectomy.Results:The incidence of PD postoperative delayed hemorrhage was 8.81％ (45/511).Univariate analysis shows:Preoperative bilirubin levels,pancreatic fistula,biliary fistula,postoperative abdominal infection are all the meaningful related factors(P＜0.05).With the application of multivariate logistic regression analysis,pancreatic fistula (OR=2.158) and abdominal infection (OR=3.051) were independent risk factors for postoperative delayed hemorrhages (P＜0.05).Conclusion:Dealing with the postoperative complications of PD like pancreatic fistula,abdominal infection and others,early detection and rapid diagnosis and correct treatment can effectively reduce the incidence of delayed hemorrhage.

BACKGROUND:Currently, it is stil controversial about the border, surrounding fascia, space of pelvic cavity, distribution of nerves and lymph nodes of the mesorectum, and the development of new technologies makes a progress in related anatomic research.
OBJECTIVE:To summarize the previous studies so as to describe clearly the progress of mesorectal anatomy and to discuss its clinical value.
METHODS: Using “rectum; mesentery; fascia; space; nerve; lymph node; total mesorectal excision (TME); clinical anatomy” as key words, a computer-based search of PubMed was done for articles related to the mesorectum and surrounding fasciae, space of pelvic cavity, distribution of nerves and lymph nodes.
RESULTS AND CONCLUSION:Fresh or frozen specimens are often used for studying the mesenterium, fascia, nerves and lymph nodes by using traditional pelvic and perineum anatomical methods. Computer-assisted anatomical dissection can combine immunostaining with computer imaging. A three-dimensional model can wel reflect the relationship among the different anatomical structures, as wel as nerve traveling and spatial location. Mesorectum is located behind the denonviliers and in the front of the sacral fascia of the rectum. Pelvic splanchnic nerve of the mesorectum is derived from the anterior sacral nerve root, runs through the presacral fascia, and enters into the neuro-fascial layervia the pesacral space, which is divided into the upper and lower parts according to the peritoneum. There are more folds in the rear of lymph nodes within the mesorectum within and near the peritoneum. There are stil a lot of controversies about anatomical relationship between the mesorectum and surrounding structures, and to elaborate these issues can provide an objective basis for guiding clinical work.