Lactic acid (LA) accumulation in tumor microenvironments (TME) has been implicated in immune suppression and tumor progress. Diverse roles of LA have been elucidated, including microenvironmental pH regulation, signal transduction, post-translational modification, and metabolic remodeling. This review summarizes LA functions within TME, focusing on the effects on tumor cells, immune cells, and stromal cells. Reducing LA levels is a potential strategy to attack cancer, which inevitably affects the physiological functions of normal tissues. Alternatively, transporting LA into the mitochondria as an energy source for immune cells is intriguing. We underscore the significance of LA in both tumor biology and immunology, proposing the burning of LA as a potential therapeutic approach to enhance antitumor immune responses.
Humans ; Tumor Microenvironment/immunology* ; Neoplasms/therapy* ; Lactic Acid/immunology* ; Mitochondria/metabolism* ; Animals ; Signal Transduction

ObjectiveTo establish a qualitative and quantitative analysis method for chemical constituents in Liu Junzitang（LJZT）， and to clarify its material basis. MethodThe chemical constituents in LJZT were analyzed by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， and the resulting compounds were identified by using databases， such as MassBank， PubChem， ChemSpider， Traditional Chinese Medicine Systems Pharmacology Database and Analytical Platform（TCMSP）， and by combining with relevant literature. UPLC was used to establish a quantitative method for analysis of 9 compounds in LJZT， including liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ. ResultBy combining the relevant literature， database and MS information， a total of 79 compounds were identified from LJZT， including 31 flavonoids， 15 terpenoids， 14 nitrogen-containing compounds， 6 phenylpropanoids， 6 organic acids and 7 other compounds. The established quantitative analytical method for the nine representative components showed good linearity within their respective linear ranges， and the precision， stability， reproducibility and recovery were in accordance with the requirements. The quantitative results showed that the contents of liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ in LJZT were 0.376 5， 2.602 1， 0.082 6， 0.128 1， 1.778 6， 0.015 7， 0.006 7， 0.030 4， 0.003 2 mg·g^-1， respectively. ConclusionThe established method can quickly， sensitively and accurately analyze the chemical constituents in LJZT， clarify that the material basis of LJZT is mainly flavonoids， terpenoids and nitrogen-containing compounds， and simultaneously determine the contents of the 9 components， which can lay a foundation for the research on quality control， mechanism and clinical application of LJZT.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca²⁺-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
Mice ; Animals ; Amyotrophic Lateral Sclerosis/pathology* ; Calcineurin/metabolism* ; Motor Neurons/pathology* ; Microfilament Proteins/metabolism* ; Cytoskeletal Proteins/metabolism*

Objective To explore the influences of continued nursing care on the recovery of intra-articular fractures of joint function of limbs and the quality of life after operation. Methods A total of 493 intra-articular fracture of limbs postoperative patients,who were discharged from our department from January 2015 to December 2016,were randomly divided into observation group and reference group.After operation,the reference group used self-management mode to practice joint functional exercise,while the observation group uses continued nursing mode to guide physical therapy to recover joint functions.After they discharged 12 weeks,we compared these two groups of patients with satisfaction of nursing care,joint function recovery and quality of life. Results After 12 weeks of operation, in observation group, the patients' joint function recovery rate was close to 79.27%(195/246), which was significantly higher than the rates 55.47%(137/247)in reference group,the difference was statistically significant(χ2=32.947,P<0.01). Respectively, the physiological function score,vigor score, mental health score, physiology role score, body pain score, health condition score, social function score and health score of the observation group in the quality of life assessment were (72.66 ± 4.41), (89.27 ± 4.10), (93.01 ± 3.05), (88.03 ± 3.19), (91.68±3.99),(76.78±4.86),(79.11±4.68),(85.57±7.07).The scores of control groups were(65.71±3.41),(64.02±4.51),(61.43±4.29),(66.49±4.52),(64.24±4.30),(62.02±6.24),(62.94±4.50),(65.02±7.72).The comparative difference of the two groups has statistical significance (t=12.48- 60.15, P<0.05). Meanwhile,in the satisfaction rate of nursing care,the great satisfaction rate of observation group(70.73%, 174/246) was much higher than reference group (37.65%, 93/247), the difference was statistically significant (χ2=59.789, P<0.01). Conclusion Offered outside continued nursing care to the intra-articular fracture of limbs postoperative patients can effectively improve the joint function of patients,their qualities of life and can considerably increase satisfaction of nursing care. Thus,it should to be clinically promoted.

Surgical site infection (SSI)following spinal surgery is the most common complications, which is devastating for both the patient and the surgeon.There is strong evidence in the literature that opti-mizing specific preoperative,intraoperative,and postoperative variables can significantly lower the risk of developing an SSI.Evidence-based approach will allow surgeons to minimize the risk of SSI and,therefore, significantly improve patient care.Here,we review the current evidence.

[ ABSTRACT] AIM:To investigate the effects of pathological products, urinary proteins and advanced glycosyla-tion end products ( AGE) produced in the progression of chronic kidney disease ( CKD) , on the structure and function of lysosomes in renal tubular epithelial cells ( TECs ) , and try to find a novel approach for preventing or delaying CKD. METHODS:The renal specimens of the untreated patients with minimal change nephrotic syndrome (MCNS), diabetic nephropathy (DN) or normal kidney were collected.The expression of lysosomal-associated membrane protein 1 (LAMP1) and cathepsin B ( CB) was studied in TECs by indirect immunofluorescent staining.Human renal tubular epithelial cell line HK-2 was incubated with 8 g/L urinary proteins or 100 mg/L AGE.The expression of LAMP1 and CB was investigated by indirect immunofluorescence and the activity of CB and cathepsin L ( CL) was measured by biochemical and enzymatic as-says.The degradation of DQ-ovalbumin was also determined.RESULTS: The lysosomal membrane permeabilization oc-curred in the TECs of MCNS and DN patients.After treatment with urinary proteins or AGE-BSA, the lysosomal membrane permeabilization of the HK-2 cells was increased.The activity of CB and CL and degradation of DQ-ovalbumin were de-creased as compared with normal control group.CONCLUSION:The digestive function of lysosome was decreased and ly-sosomal membrane permeabilization occurred in the TECs exposed to urinary proteins and AGE, which might be a key factor to induce the tubulointerstitial fibrosis.

Objective To explore the symptoms of anxiety,family structure,and the distribution features of family about in-patients.And to find out the influence of the family structure on in-patients' symptoms of anxiety.The results would provide evidentiary support and suggestions for in-patients to improve quality of life and for prevention and intervention of anxiety.Methods Family table was used to register the family structure which was classified as the nuclear family,stem/expended family and other classification.The anxiety of in-patients was measured by self-rating anxiety scale.Results A total of 512 cases of in-patients completed the survey,there were 483 valid questionnaires.The rate of effective questionnaire was 94.34％.In family structure of in-patients,core family accounted for 48.65％,stem/expended family was 36.85％.The sex of family structure showed significant difference,the female proportion of the nuclear family was significantly higher than male.Among all in-patients,78.05％ did not have anxiety,low-level,medium-level,and severe anxiety showed no significant differences.The effects of anxiety on family structure had significant differences.The anxiety level of stem family was relatively higher.Conclusions Economic development and the population flow due to industrialization and globalization changed family structure of our country,especially in coastal de-velopment cities with fast economic development,fast-paced and stressful work,and it may affect the influ-ence of Chinese traditional family structure on anxiety of the in-patients.

V infection group than in no infection group,while positive rate of other autoantibodies was not statistically different between the two groups.Conclusion Renal EBV infection may involve in the pathogenesis of LN by inducing the production of anti-Sm-Ab.

OBJECTIVE To investigate the epidemiology of bacterial infections isolated from liver disease patients with septic shock and analyze the antimicrobial susceptibility of major pathogens to provide reference for clinical therapy. METHODS A retrospective survey was conducted in 83 liver disease patients with septic shock of our hospital from Jan 2005 to Aug 2006. Identification and susceptibility of pathogens were assayed by MicroScan Auto-4 System. RESULTS The infection was frequently identified in intra-abdominal cavity (73.5%),blood stream (24.1%) or respiratory tract (13.3%). The top 3 pathogens were Escherichia coli (36.6%),Klebsiella pneumoniae (15.9%) and Staphylococcus aureus (6.1%). Gram-negative bacilli were usually resistant to multiple antimicrobial agents,but less resistant to imipenem,levofloxacin or piperacillin-tazobactam. Extended-spectrum ?-lactamases (ESBLs) positive rates of E. coli and K. pneumoniae were 53.3% and 7.7%. Asprergillus and Candida glabrata were the predominant pathogens from fungal infections,and they were mostly resistant to fluconazole. CONCLUSIONS Pathogens of liver disease patients with septic shock are mostly multi-drug resistant. The microbiological surveillance is important for guiding clinical therapy.

Aim To investigate the effects of Panax Notoginsenosides(PNS) on the gene expression and protein excretion of TGF-?_1 and CTGF of human renal tubular epithelial cell induced by uremic serum in vitro.Methods Forty sera from CRF patients and twenty sera from healthy volunteers were collected,gently mixed,inactived and separated respectively in steriled condition.HK-2 Cells were cultured in RPMI-1640 medium with 10% newborn calves serum and subcultured routinely.They were differentiated by phase contrast microscope and scanning electron microscope detection and cytokeratin18(CK-18) immunohistochemistry method.The protein levels of TGF-?_1 were examined by enzyme-linked immunoadsordent assay(ELISA).The protein levels of CTGF were examined by Western Bloting assay.The gene expression of TGF-?_1 and CTGF was detected by Semi-quantitative reverse trainscriptase polymerase chain reaction(RT-PCR).Results TGF-?_1 and CTGF gene expression and protein level were increased in 10% uremic serum groups compared with that of normal control group(P