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

Thyrotoxic periodic paralysis(TPP) is a rare but potentially life-threatening complication of thyrotoxicosis. TPP secondary to thyrotoxicosis factitia(TF) is exceptionally uncommon. Here, we report the case of a 31-year-old female who developed TF and subsequent TPP after taking laxatives containing unknown ingredients. The patient presented with acute onset of quadriplegia. Laboratory investigations revealed severe hypokalemia(serum potassium 1.47mmol/L), thyrotoxicosis[thyroid stimulating hormone(TSH)<0.005 mIU/L, free thyroxine(FT 4) 30.84 pmol/L, free triiodothyronine(FT 3) 7.71 pmol/L], and a decreased thyroglobulin level(3.08 ng/mL). The patient′s symptoms resolved rapidly following potassium supplementation, and thyroid function gradually normalized after discontinuation of the suspected medication. This case highlights the importance of considering TF in the differential diagnosis of TPP, particularly in patients with a history of unknown medication use. It also underscores the diagnostic value of thyroglobulin measurement in identifying TF and outlines clinical strategies for the management of TF-induced TPP.

Thyrotoxic periodic paralysis(TPP) is a rare but potentially life-threatening complication of thyrotoxicosis. TPP secondary to thyrotoxicosis factitia(TF) is exceptionally uncommon. Here, we report the case of a 31-year-old female who developed TF and subsequent TPP after taking laxatives containing unknown ingredients. The patient presented with acute onset of quadriplegia. Laboratory investigations revealed severe hypokalemia(serum potassium 1.47mmol/L), thyrotoxicosis[thyroid stimulating hormone(TSH)<0.005 mIU/L, free thyroxine(FT 4) 30.84 pmol/L, free triiodothyronine(FT 3) 7.71 pmol/L], and a decreased thyroglobulin level(3.08 ng/mL). The patient′s symptoms resolved rapidly following potassium supplementation, and thyroid function gradually normalized after discontinuation of the suspected medication. This case highlights the importance of considering TF in the differential diagnosis of TPP, particularly in patients with a history of unknown medication use. It also underscores the diagnostic value of thyroglobulin measurement in identifying TF and outlines clinical strategies for the management of TF-induced TPP.

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.

Objective Measuring effects of obsessive-compulsive symptom on resting-state functional connectivity changes for children with first-episode schizophrenia. Methods Resting-state functional magnetic resonance imaging data analysis toolkit (REST) were employed to analyze resting-state functional magnetic resonance imaging data. The data were obtained from 51 children with first-episode schizophrenia and 30 healthy controls (HCG). The children with schizophrenia were divided into two groups, 21 ones with obsessive-compulsive symptom (OCG), and 30 ones without obsessive-compulsive symptom (NOCG). The right side of the medial frontal gyrus was selected as seed point to analyze its functional connectivity with the whole brain, utilizing REST. And the MNI coordinate was set as (18, 42, 27). Connectivity differences between any two groups were compared by two-sample t-test. Results Compared with HCG, functional connectivity with the left frontal lobe in OCG and NOCG was strengthened, while functional connectivity with the left precentral gyrus, the left inferior frontal gyrus, the left medial frontal gyrus, and the right frontal lobe was weakened (t=4.141,-4.223,-4.833,-4.636,-3.859, P<0.05). In NOCG, functional connectivity with the right middle occipital gyrus and parietal, the left inferior frontal gyrus and precentral gyrus was enhanced, while functional connectivity with the left lentiform nucleus, the left medial frontal gyrus, the left cingulate gyrus, the right lentiform nucleus, the right brainstem and frontal lobe was weakened(t=3.735, 4.321, 3.453, 4.393,-3.134,-3.987,-3.456,-4.739,-4.034,-4.322,P<0.05). In OCG, functional connectivity with the right middle frontal gyrus, and the left frontal lobe was enhanced, but connectivity with the right cerebellum anterior lobe, and the right precuneus was weakened (t=4.493, 4.403, 4.259,-3.513,-3.522, P<0.05). In OCG, compared with NOCG, functional connectivity with brain regions including the right middle frontal gyrus, the right lentiform nucleus, and the right inferior parietal lobule was strengthened, while functional connectivity with brain regions including the right cerebellum anterior lobe, and the right precuneus was weakened (t=4.493, 4.403, 4.259,-3.513,-3.522, P<0.05). Conclusions For children with first-episode schizophrenia with and without obsessive-compulsive symptom, there may be differences in resting-state functional connectivity disorder. Obsessive-compulsive symptom may have effect on resting-state functional connectivity changes for children in first-episode schizophrenia.

Objective To explore neurological soft signs (NSS) and its' relationship with the DISC1 gene polymorphism in childhood schizophrenia.Methods 300 childhood-onset schizophrenia patients,and 270 gender/age matched healthy controls were enrolled in this study.The genotype of SNP rs821597 was detected by polymerase chain reaction based restriction fragment length polymorphism analysis.And the two groups were assessed with the soft signs examination based on the Cambridge Neurological Inventory.Results Both the genotype (AA:90(30.0％),AG:141(47.1％),GG:69(22.9％) vs.AA:58(21.3％),AG:136(50.4％),GG:76(28.3％)) and allele frequencies (A:321(53.5％),G:279(46.5％) vs.A:252(46.7％),G:288(53.3％)) were significantly different between patients and controls (x2=6.54,6.12;P=0.040,0.010).After multiple test correction,the childhood-onset schizophrenia patients showed higher rates of positive sign than the control group in left finger-thumb tapping,finger thumb opposition and fingeragnosia,right diadochokinesis,left and right fist-edge-palm test and graphesthesia oseretsk test (x2=15.42,21.31,10.47,17.66,23.21,19.16,21.49,74.64,33.78; all P＜0.002),and the motor coordination scores,sensory integration scores,disinhibition scores and the NSS total scores(Z=-9.336,-6.736,-2.951,-8.861; all P＜0.05),which were analyzed by nonparameter test.There were significant differences in left and right finger thumb opposition,diadochokinesis,stereognosis and mirror movement of finger thumb opposition,right graphesthesia and fist-edge-palm test,oseretsky test,wink(x2=24.89,25.22,50.08,29.41,20.00,46.27,14.09,26.75,33.75,63.54,15.11,34.20; all P＜0.002),motor coordination scores,NSS total scores (Z=-4.400,-3.580;both P＜0.05) between different genotypes carriers.The AA and AG genotypes carriers in patients showed significant higher NSS positive rates,NSS total scores and motor coordination scores than the GG carriers by Q test.Conclusions The rs821597 gene polymorphism is possibly associated with childhood-onset schizophrenia disease and the patients' NSS,which means the childhood-onset schizophrenia patients showing more NSS abnormalities than the healthy controls.The A allele carriers show higher risk to schizophrenia disease,and have more NSS positive symptoms.

Objective Measuring effects of obsessive-compulsive symptom on resting-state functional connectivity changes for children with first-episode schizophrenia. Methods Resting-state functional magnetic resonance imaging data analysis toolkit (REST) were employed to analyze resting-state functional magnetic resonance imaging data. The data were obtained from 51 children with first-episode schizophrenia and 30 healthy controls (HCG). The children with schizophrenia were divided into two groups, 21 ones with obsessive-compulsive symptom (OCG), and 30 ones without obsessive-compulsive symptom (NOCG). The right side of the medial frontal gyrus was selected as seed point to analyze its functional connectivity with the whole brain, utilizing REST. And the MNI coordinate was set as (18, 42, 27). Connectivity differences between any two groups were compared by two-sample t-test. Results Compared with HCG, functional connectivity with the left frontal lobe in OCG and NOCG was strengthened, while functional connectivity with the left precentral gyrus, the left inferior frontal gyrus, the left medial frontal gyrus, and the right frontal lobe was weakened (t=4.141,-4.223,-4.833,-4.636,-3.859, P<0.05). In NOCG, functional connectivity with the right middle occipital gyrus and parietal, the left inferior frontal gyrus and precentral gyrus was enhanced, while functional connectivity with the left lentiform nucleus, the left medial frontal gyrus, the left cingulate gyrus, the right lentiform nucleus, the right brainstem and frontal lobe was weakened(t=3.735, 4.321, 3.453, 4.393,-3.134,-3.987,-3.456,-4.739,-4.034,-4.322,P<0.05). In OCG, functional connectivity with the right middle frontal gyrus, and the left frontal lobe was enhanced, but connectivity with the right cerebellum anterior lobe, and the right precuneus was weakened (t=4.493, 4.403, 4.259,-3.513,-3.522, P<0.05). In OCG, compared with NOCG, functional connectivity with brain regions including the right middle frontal gyrus, the right lentiform nucleus, and the right inferior parietal lobule was strengthened, while functional connectivity with brain regions including the right cerebellum anterior lobe, and the right precuneus was weakened (t=4.493, 4.403, 4.259,-3.513,-3.522, P<0.05). Conclusions For children with first-episode schizophrenia with and without obsessive-compulsive symptom, there may be differences in resting-state functional connectivity disorder. Obsessive-compulsive symptom may have effect on resting-state functional connectivity changes for children in first-episode schizophrenia.