Objective: To investigate the epidemiological characteristics and spatial-temporal clustering of severe fever with thrombocytopenia syndrome (SFTS) in Huai'an City, Jiangsu Province from 2011 to 2024, so as to provide a basis for optimizing local SFTS prevention and control strategies, and identifying high-risk areas and key populations. Methods: Data on SFTS incidence and deaths in Huai'an City from 2011 to 2024 were collected from the Infectious Disease Reporting Information System of the Chinese Disease Prevention and Control Information System. The reported incidence, mortality, and fatality rates were calculated. Descriptive analysis was performed on temporal, population, and regional distribution. The average annual percent change (AAPC) was used to analyze the trend in the reported incidence of SFTS. Global and local spatial autocorrelation analyses were employed to examine the spatial distribution patterns and spatial association patterns of SFTS incidence while spatio-temporal scanning analyses was used to assess the spatial-temporal clustering of SFTS. Results: A total of 337 SFTS cases were reported in Huai'an City from 2011 to 2024, with the reported incidence rising from 0.17/100 000 to 1.88/100 000. There were 20 deaths, with an average annual mortality of 0.03/100 000, and a fatality rate of 5.93%. The incidence showed obvious seasonality, with a peak in May and June (148 cases, accounting for 43.92%). Spring and summer accounted for 107 cases (31.75%) and 159 cases (47.18%), respectively. The reported SFTS cases were mainly male, farmers, and individuals aged ≥41 years, accounting for 56.38%, 79.23%, and 96.74%, respectively. The population distribution of death cases was basically consistent with that of incident cases. Xuyi County was a high-incidence area, with a total of 332 reported cases, accounting for 98.52%. All death cases were reported in this county. Spatial autocorrelation analyses revealed a positive spatial correlation in SFTS incidence from 2019 to 2024, with Moran's I values ranging from 0.214 to 0.336 (all P<0.05). Heqiao Town, Tianquanhu Town, and Guiwu Town in Xuyi County were identified as high-high clustering areas. Spatio-temporal scanning analyses showed that cluster 1 was consistent with the high-high clustering areas, with an aggregation time from the second quarter of 2019 to the second quarter of 2022. Conclusions From 2011 to 2024, the reported incidence of SFTS in Huai'an City showed an upward trend, with a high incidence in spring and summer. Males, farmers, and the middle-aged and elderly population were the key populations for prevention and control. Xuyi County was the key area for prevention and control.

ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets （TG） and the molecular mechanism of compound glycyrrhizin tablets （CG） in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights， male Sprague-Dawley （SD） rats were randomly grouped as follows： control （pure water）， low-dose TG （TG-L， 189.0 mg·kg^-1·d^-1）， high-dose TG （TG-H， 472.5 mg·kg^-1·d^-1）， TG-L+CG （189.0 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， and TG-H+CG （472.5 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration， the mRNA and protein levels of liver X receptor-alpha （LXR-α）， low-density lipoprotein receptor （LDLR）， adenosine triphosphate-binding cassette transporter A1 （ABCA1）， adenosine triphosphate-binding cassette transporter G1 （ABCG1）， 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， cholesterol 12α-hydroxylase （CYP8B1）， and sterol 27-hydroxylase （CYP27A1） in the liver tissue were determined by Real-time PCR and Western blotting， respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMG-CoAR）， a regulatory enzyme of cholesterol synthesis， was measured by enzyme-linked immunosorbent assay （ELISA）. HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically， HepG2 cells were grouped as follows： Low-dose TG （TG-l， 15 mg·L^-1）， medium-dose TG （TG-m， 45 mg·L^-1）， high-dose TG （TG-h， 135 mg·L^-1）， fenofibrate （FB， 10 μmol·L^-1）， CG extract， TG-h+FB （135 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-m+FB （45 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-l+FB （15 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-h+CG （135 mg·L^-1 TG + 60 μmol·L^-1 CG）， TG-m+CG （45 mg·L^-1 TG + 60 μmol·L^-1 CG）， and TG-l+CG （15 mg·L^-1 TG + 60 μmol·L^-1 CG）. The mRNA and protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting， respectively. ResultsThe rat experiment showed that compared with the control group， the TG-H group showed down-regulated mRNA levels of CYP7A1， CYP8B1， and CYP27A1 in the liver tissue （P<0.05， P<0.01）， which were up-regulated by the application of CG （P<0.05， P<0.01）， and the TG-H+CG group showed up-regulated mRNA level of LDLR （P<0.01）. Compared with the control group， the TG-L and TG-H groups showed down-regulated protein levels of LDLR， CYP7A1， and CYP8B1 in the liver tissue （P<0.05， P<0.01）. In addition， the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups， respectively （P<0.05）. Compared with TG alone， TG+CG up-regulated the protein levels of ABCG1 and LDLR （P<0.05， P<0.01）， and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated （P<0.05， P<0.01）. The cell experiment showed that compared with the control group， the TG-h group presented up-regulated mRNA level of LXR-α （P<0.01）， and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 （P<0.01） and up-regulated mRNA level of CYP27A1 （P<0.01） in HepG2 cells. The combination of CG with TG restored the above changes （P<0.01）. Western blotting results showed that compared with the control group， the TG-m and TG-h groups showed down-regulated protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells （P<0.01）. Compared with the TG-h group， the TG-h+CG group showed up-regulated protein level of LDLR （P<0.05）. Compared with the TG-m group， the TG-m+CG group showcased up-regulated protein levels of LDLR， ABCG1， CYP7A1， and CYP27A1 （P<0.05， P<0.01）. ConclusionThe administration of TG at 189.0， 472.5 mg·kg^-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux， endocytosis， and cholesterol biotransformation in hepatocytes， leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α， LDLR， ABCG1， CYP7A1， CYP8B1， and CYP27A1 to promote cholesterol biotransformation.

AIM: To investigate the abnormal conditions and change patterns of accommodative facility in patients with different refractive states before and after small incision lenticule extraction(SMILE)surgery.METHODS:A prospective clinical cohort study was conducted. A total of 59 patients(118 eyes)who underwent SMILE surgery and had visual function files established in our hospital from June to December 2023 were randomly selected, including 37 males and 22 females, aged 18-35 years(with an average age of 25.19±5.65 years). According to the preoperative spherical equivalent(SE), they were divided into two groups: the low-to-moderate myopia group(SE≥-6.00 DS)with 40 patients(80 eyes), and the high myopia group(SE<-6.00 DS)with 19 patients(38 eyes). The monocular and binocular accommodative facility before surgery and at 1 wk and 1 mo after surgery were compared, and the changes in accommodative facility before and after SMILE surgery in the two groups of patients were analyzed.RESULTS:All surgeries were completed successfully. In the low-to-moderate myopia group, 33 cases(66 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 17.5%(7/40). In the high myopia group, 15 patients(30 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 21.1%(4/19). After SMILE surgery, the uncorrected visual acuity and SE of both low-to-moderate myopia and high myopia were significantly improved(all P<0.05). The accommodative facility of the right eyes in all the patients at 1 mo after surgery was better than that before surgery and at 1 wk after surgery(P=0.002, 0.006), the accommodative facility of the left eyes was significantly increased at 1 mo after surgery than that at 1 wk after surgery(P=0.005), and the binocular accommodative facility at 1 mo after surgery was significantly increased compared with that before surgery(P<0.017). Furthermore, there were statistical significance in accommodative facility of the right eyes in the low-to-moderate group at 1 mo compared with that before surgery and at 1 wk after surgery(P=0.011, 0.004); it was significantly increased in the left eyes at 1 mo after surgery compared with that at 1 wk after surgery(P=0.001), and binocular accommodative facility at 1 mo after surgery was significantly better than that before surgery(P<0.001). Furthermore, there was no statistical significance in the right, left and binocular accommodative facility of patients in the high myopia group(all P>0.017).CONCLUSION: After SMILE surgery, the monocular accommodative facility shows a transient decrease and then exceeds the preoperative level at 1 mo after surgery, and the binocular accommodative facility gradually improves after surgery. SMILE surgery has a positive impact on the monocular and binocular accommodative facility in patients with low-to-moderate myopia, but has no significant impact on the accommodative facility in patients with high myopia. It is of clinical significance to strengthen the detection of monocular and binocular accommodative facility before and after SMILE surgery.

Objective To investigate the bone protective effects and underlying mechanisms of 900MHz radiofrequency radiation (RF) at different power densities (50, 150, and 450 μW/cm²) on an ovariectomy-induced osteoporosis mouse model. Methods Sixty 3-month-old C57BL/6 female mice were randomly divided into Sham group (sham exposure), OVX group (ovariectomy), OVX + LRF group (OVX + 50 μW/cm² RF), OVX + MRF group (OVX + 150 μW/cm² RF), OVX + HRF group (OVX + 450 μW/cm² RF), and OVX + E2 group (OVX + estradiol). Ovariectomized mice in the OVX + RF groups were exposed to RF of varying power densities for 4 hours daily. Ovariectomized mice in the OVX + E2 group received intramuscular injections of estradiol (0.04 mg/kg) every two days. After four weeks of intervention, Micro-CT, ELISA, RT-PCR, and immunohistochemistry were employed to analyze bone density, bone microstructure, serum bone metabolic markers, and the expression of related genes and proteins. Results Compared with the Sham group, the OVX group showed significantly decreased bone mineral density (BMD) and bone microstructure indicators such as BV, BV/TV, Tb.Th, and Tb.N, significantly increased bone microstructure indicator Tb.Sp, significantly decreased serum estradiol, significantly increased serum CTX-I, TRACP-5b, BGP, and OPG, significantly increased Nfatc1 and Runx2 mRNAs, and significantly increased OPG and RANKL. Compared with the OVX group, the OVX + MRF group and OVX + E2 group exhibited significantly increased BMD, BV, BV/TV, Tb.Th, and Tb.N, significantly decreased Tb.Sp, significantly increased serum OPG, Runx2 mRNA, and OPG, and significantly decreased serum CTX-I, TRACP-5b, Nfatc1 mRNA, and RANKL. Compared with the OVX group, the OVX + LRF group showed significantly increased cortical bone BMD and Tb.Th, the OVX + HRF group showed significantly increased cortical bone BMD and serum CTX-I and TRACP-5b, and the OVX + MRF group showed significantly increased serum BGP. Among the three power densities, the 150 μW/cm² RF showed the most significant effect. Conclusion The 150 μw/cm² 900 MHz RF can counteract the abnormalities in serum bone metabolism biomarkers, the decrease in BMD, the degeneration of bone microstructure, and the increase in bone resorption caused by ovariectomy in mice.

AIM: To analyze the changes in binocular visual function before and after small incision lenticule extraction(SMILE)in patients with different degrees of myopia.METHODS:A prospective non-randomized controlled study was conducted. A total of 94 patients(188 eyes)who visited the refractive outpatient department of the ophthalmology department of the General Hospital of the PLA from June 2022 to June 2023 and voluntarily chose SMILE were consecutively included. They were grouped according to the degree of myopia, including 24 cases(48 eyes)in the low myopia group(-3.00 D

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

Immune suppression in the tumor microenvironment (TME) is closely related to abnormal glycolysis. Tumor cells gain metabolic advantages and suppress immune responses through the "Warburg effect". Traditional Chinese medicine (TCM) has been shown to regulate key glycolysis enzymes (such as HK2 and PKM2), metabolic signaling pathways (such as PI3K/AKT/mTOR, HIF-1α) and non-coding RNAs at multiple targets, thus synergistically inhibiting lactate accumulation, improving vascular abnormalities, and relieving metabolic inhibition of immune cells. Studies have shown that TCM monomers and formulas can promote immune cell infiltration and functions, improve metabolic microenvironment, and with the assistance by the nano-delivery system, enhance the precision of treatment. However, the dynamic mechanism of the interaction between TCM-regulated glycolysis and TME has not been fully elucidated, for which single-cell sequencing and other technologies provide important technical support to facilitate in-depth analysis and clinical translational research. Future studies should be focused on the synergistic strategy of "metabolic reprogramming-immune activation" to provide new insights into the mechanisms of tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Glycolysis/drug effects* ; Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

Objective: To investigate the significant factors influencing the need for perioperative blood transfusion in patients undergoing hepatectomy. Methods: Medical records of patients who underwent elective hepatectomy in our hospital from January 2020 to December 2021 were retrospectively collected. Variables associated with transfusion were analyzed using traditional logistic regression (LR) and machine learning algorithm, the Classification and Regression Tree (CRT). The predictive values of the two methods were compared by the area under the curve (AUC) of the ROC curve. Results: Among the 402 patients, 82(20.4%) received blood transfusions. Multivariable logistic regression analysis identified several risk factors for perioperative blood transfusion, including vascular invasion, preoperative hemoglobin level, intraoperative blood loss, duration of surgery, postoperative hemoglobin level, and postoperative complications (P<0.05). In the CRT model for predicting blood transfusion, intraoperative blood loss (cutoff: 450 mL) was the parent node, with preoperative Hb, postoperative complications, and hospital stay as child nodes. The LR model demonstrated superior predictive performance compared to the CRT model, with an AUC of 0.971 (95% CI: 0.956-0.985) vs 0.937 (95% CI: 0.909-0.965). The difference in AUC between the two methods was statistically significant (P<0.05). Conclusion: Although the CRT model did not outperform logistic regression in overall predictive accuracy, it still provides a valuable tool for assisting clinicians in making decisions about blood transfusion in the perioperative period of hepatectomy, thereby facilitating more individualized guidance for preoperative blood preparation in clinical practice.