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

Objective To evaluate the relationship between systemic inflammation makers and bone mineral density(BMD)in male patients with type 2 diabetes(T2DM).Methods A total of 261 male patients with T2DM were selected and divided into three groups based on diagnostic criteria:the normal bone mass group(96 cases),the reduced bone mass group(111 cases)and the osteoporosis group(54 cases).Differences in systemic inflammation markers and bone metabolic markers were compared between the three groups.Multivariate ordered Logistic regression analysis was used to investigate factors influencing the progression from normal bone mass to osteoporosis in male patients with T2DM.Receiver operating characteristic(ROC)curves were used to evaluate the predictive value of inflammatory markers for osteoporosis in male patients with T2DM.Correlation analysis was conducted to investigate the correlation between inflammatory markers and BMD and bone turnover markers(BTM)in male patients with T2DM.Results Platelet count(PLT),platelet-to-lymphocyte ratio(PLR),systemic inflammatory index(SII)and neutrophil-to-lymphocyte ratio(NLR)were significantly higher in the osteoporosis group than those in the normal bone mass group(P＜0.05).Multivariate ordered Logistic regression analysis showed that PLR and SII were risk factors for the progression from normal bone mass to osteoporosis in male patients with T2DM(P＜0.05).The area under the ROC curve of PLR was 0.590,and the cut-off value was 96.67.The area under the curve of SII was 0.613,with a cut-off value of 307.9,and the area under the combined curve of the above two indicators was 0.612.In patients with osteoporosis and osteopenia,SII,PLR and PLT were negatively correlated with L1-4 BMD and left hip BMD(P＜0.05).SII was also negatively correlated with left femoral neck BMD(P＜0.05).Conclusion Inflammatory markers PLR and SII have predictive values for the progression from normal bone mass to bone loss and osteoporosis in male patients with T2DM.

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.

Objective To evaluate the relationship between systemic inflammation makers and bone mineral density(BMD)in male patients with type 2 diabetes(T2DM).Methods A total of 261 male patients with T2DM were selected and divided into three groups based on diagnostic criteria:the normal bone mass group(96 cases),the reduced bone mass group(111 cases)and the osteoporosis group(54 cases).Differences in systemic inflammation markers and bone metabolic markers were compared between the three groups.Multivariate ordered Logistic regression analysis was used to investigate factors influencing the progression from normal bone mass to osteoporosis in male patients with T2DM.Receiver operating characteristic(ROC)curves were used to evaluate the predictive value of inflammatory markers for osteoporosis in male patients with T2DM.Correlation analysis was conducted to investigate the correlation between inflammatory markers and BMD and bone turnover markers(BTM)in male patients with T2DM.Results Platelet count(PLT),platelet-to-lymphocyte ratio(PLR),systemic inflammatory index(SII)and neutrophil-to-lymphocyte ratio(NLR)were significantly higher in the osteoporosis group than those in the normal bone mass group(P＜0.05).Multivariate ordered Logistic regression analysis showed that PLR and SII were risk factors for the progression from normal bone mass to osteoporosis in male patients with T2DM(P＜0.05).The area under the ROC curve of PLR was 0.590,and the cut-off value was 96.67.The area under the curve of SII was 0.613,with a cut-off value of 307.9,and the area under the combined curve of the above two indicators was 0.612.In patients with osteoporosis and osteopenia,SII,PLR and PLT were negatively correlated with L1-4 BMD and left hip BMD(P＜0.05).SII was also negatively correlated with left femoral neck BMD(P＜0.05).Conclusion Inflammatory markers PLR and SII have predictive values for the progression from normal bone mass to bone loss and osteoporosis in male patients with T2DM.

In animal experiments, ischemic stroke is usually induced through middle cerebral artery occlusion (MCAO), and quality assessment of this procedure is crucial. However, an accurate assessment method based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is still lacking. The difficulty lies in the inconsistent preprocessing pipeline, biased intensity normalization, or unclear spatiotemporal uptake of FDG. Here, we propose an image feature-based protocol to assess the quality of the procedure using a 3D scale-invariant feature transform and support vector machine. This feature-based protocol provides a convenient, accurate, and reliable tool to assess the quality of the MCAO procedure in FDG PET studies. Compared with existing approaches, the proposed protocol is fully quantitative, objective, automatic, and bypasses the intensity normalization step. An online interface was constructed to check images and obtain assessment results.
Animals ; Fluorodeoxyglucose F18 ; Infarction, Middle Cerebral Artery/diagnostic imaging* ; Positron-Emission Tomography/methods*

Objective: The objective of this study was to present the real-world patients’ portrait, and the results of niraparib treatment in China. Methods: This study included 142 patients treated with niraparib from 8 hospitals in China between December 2018 and September 2021. Patients’ characteristics were summarized. The efficacy and safety in first-line maintenance (1L-M), platinum-sensitive recurrence maintenance (PSR-M), and treatment for ovarian cancer were evaluated. Survival outcomes and the factors influencing progression-free survival (PFS) were estimated. Results: The 93 patients received Niraparib as 1L-M, 31 as PSR-M and 18 as salvage. BRCA status was wild type or unknown in 87.3% of patients. With a median follow-up time of 8.7 months, the median PFS (mPFS) for 1L-M has not yet been reached, and the mPFS for PSR-M and salvage therapy was 10.5 and 5.7 months, respectively. Responses to last chemotherapy and cancer antigen 125 value before taking niraparib were 2 important factors affecting PFS among 1L and PSR patients. The 12.7% (18/142) of patients experienced grade ≥3 hematologic adverse events and 23.2% experienced dose adjustment. It was noteworthy that when the interval of chemotherapy and niraparib <21 days, the incidence of grade ≥3 adverse events increased significantly (p=0.0355). Conclusion Generally, niraparib was effective and well tolerated, which was consistent with the results of prospective trials. However, in real world, it was more inclined to use niraparib in late-line treatment without genetic testing.

The cultivation and production of cucumber are seriously affected by downy mildew caused by Pseudoperonospora cubensis. Downy mildew damages leaves, stems and inflorescences, and then reduces the yield and quality of cucumber. This review summarized the research advances in cucumber downy mildew, including pathogen detection and defense pathways, regulatory factors, mining of pathogens-resistant candidate genes, proteomic and genomic analysis, and development of QTL remarks. This review may facilitate clarifying the resistance mechanisms of cucumber to downy mildew.
Cucumis sativus/genetics* ; Oomycetes/genetics* ; Peronospora ; Plant Diseases/genetics* ; Proteomics

Flowering is a critical transitional stage during plant growth and development, and is closely related to seed production and crop yield. The flowering transition is regulated by complex genetic networks, whereas many flowering-related genes generate multiple transcripts through alternative splicing to regulate flowering time. This paper summarizes the molecular mechanisms of alternative splicing in regulating plant flowering from several perspectives, future research directions are also envisioned.
Alternative Splicing/genetics* ; Arabidopsis/metabolism* ; Arabidopsis Proteins/genetics* ; Flowers/genetics*

Objective To observe the changes of renal tubular injury and the extent of interstitial fibrosis in the C57BL/6 mouse models of chronic kidney disease(CKD),and provide experimental animal evidence for study of the pro-gression of acute kidney injury(AKI)to chronic kidney disease as well as its mechanisms. Methods Twenty-four 8-week-old male C57BL/6 mice were randomly and equally divided into control group, low-dose, medium-dose, and high-dose cisplatin groups,6 mice in each group. Mice in the cisplatin groups were administrated with 5,7 or 10 mg/kg cispla-tin by intraperitoneal injection once a week for 4 weeks. Plasma creatinine and 24-hour urinary protein were detected to as-sess the renal function. The mice were sacrificed, and plasma and kidney samples were collected for subsequent tests. Pathological changes were observed using periodic acid-Schiff(PAS)staining. To evaluate renal tubules injury, the ex-pression of kidney injury molecule 1(KIM-1)was examined by immunohistochemistry and the level of urinary N-Acetyl-β-D-glucosaminidase was detected with a commercial kit. The infiltration of CD3-positive T cells and F4/80-positive macro-phages was observed by immunohistochemistry(IHC)and immunofluorescence. The expression of collagen I and α-smooth muscle actin(α-SMA)were tested by immunohistochemistry to assess the renal fibrosis, while total kidney collagen was detected by Picrosirius red staining. Results In contrast to the normal control group,the kidney injury became more seri-ous in the cisplatin-treated mice as cisplatin concentration increased. Particularly,significant kidney damage was observed in the high-dose cisplatin group. Compared with the control group,the plasma creatinine and 24-hour urinary protein were significantly increased in the high-dose cisplatin group(P<0.05 and P<0.001)indicating impaired renal function. Mor-phologically,numerous clear vacuoles and necrosis were present in renal tubule epithelial cells in the high-dose cisplatin group. The expression of KIM-1 was markedly up-regulated and the level of urinary NAG was elevated. Infiltration of CD3-positive T cells and F4/80-positive macrophages was enhanced in the mice of high-dose cisplatin group. Data from immuno-histochemistry and picrosirius red staining showed that mice of the high-dose cisplatin group developed renal fibrosis evi-denced by markedly up-regulated expression of collagen I and α-SMA. Conclusions Repeated administration of 10 mg /kg cisplatin for 4 weeks can induce chronic renal insufficiency in mice,which may serve as a novel model for the research on underlying mechanisms of progression from acute kidney injury to chronic kidney disease.