Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

Immunotherapy represents the third revolution in the pharmacological treatment of tumors and has demonstrated considerable efficacy in the management of malignant solid tumors, including melanoma and lung cancer. By contrast, breast cancer is frequently categorized as a “cold tumor” because of its limited immunogenicity and immunoreactivity, which hinder research progress and clinical outcomes in immunotherapy. Only a small proportion of patients derive benefits from immunotherapeutic interventions, and the development of drug resistance remains a concern. In this regard, novel strategies should be explored for converting immunologically inert “cold tumors” into immunologically active “hot tumors”, thereby expanding the population that will benefit from breast cancer immunotherapy. This study reviews new strategies to transform breast cancer from “cold tumor” to “hot tumor”. Strategies include enhancing the expression of tumor antigens, promoting immune infiltration, and reversing the immunosuppressive microenvironment. Results also emphasize the importance of comprehensive treatment to enhance systemic immunity.

Objective To analyze the prognosis of elderly patients with community-acquired pneumonia (CAP) and its correlation with serum angiopoietin 2 (Ang-2), activated protein C (APC) and pentraxin 3 (PTX3) levels. Methods A total of 508 elderly patients with CAP in the hospital from March 2021 to March 2024 were divided into death group (n=104) and survival group (n=404) according to the survival status at 28 days after admission. Another 110 healthy subjects with physical examination were included in the control group. The levels of serum Ang-2, APC and PTX3 were compared, and their correlation with prognosis was explored by Pearson correlation analysis. Results In this study, 404 cases survived after 28 days and 104 cases died. The levels of C-reactive protein, procalcitonin and interleukin-8 and the proportion of severe condition in the survival group were lower than those in the death group (P<0.05). The level of serum APC in the case group and the death group was lower than that in the control group and the survival group (P<0.05), while the levels of Ang-2 and PTX3 were higher than those in the control group and the survival group (P<0.05), respectively. Serum APC level was negatively correlated with community-acquired pneumonia in the elderly CAP (r=-0.476, P<0.05), while Ang-2 and PTX3 were positively correlated with prognosis (r=0.489, 0.502, P<0.05). Conclusion Serum levels of Ang-2 and APC in elderly patients with CAP are decreased and the level of PTX3 is increased. Serum Ang-2 and APC levels are negatively correlated with elderly CAP, and PTX3 is positively correlated with prognosis.

Cancer represents a significant disease that profoundly impacts human health and longevity. Projections indicate a 47% increase in the global cancer burden by 2040 compared to 2020, accompanied by a further rise in the associated economic burden. Consequently, there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer. Natural products (NPs) play a crucial role in the identification and development of anticancer therapeutics. This study identified ustusolate E (UE) and its analog 11α-hydroxy-ustusolate E (HUE) from strain Aspergilluscalidoustus TJ403-EL05, and examined their antitumor activities and mechanisms of action. The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS (human gastric cancer cells) and 786-O (human renal clear cell carcinoma cells), induced irreversible DNA damage, blocked the cell cycle at the G₂/M phase, and further induced apoptosis in tumor cells. To the best of the authors' knowledge, this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms. The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.
Humans ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Tumor Suppressor Protein p53/genetics* ; Cell Proliferation/drug effects* ; Antineoplastic Agents/pharmacology* ; Sesquiterpenes/pharmacology* ; Aspergillus/chemistry*

Objective To explore whether renal denervation (RDN) could improve the left ventricular ejection fraction (LVEF) of patients with heart failure (HF) on the basis of guideline-directed management and therapy (GDMT). Methods From January 1, 2023 to August 31, 2024, HF patients diagnosed as dilated cardiomyopathy (DCM) who underwent RDN in the Second Affiliated Hospital of Chongqing Medical University were retrospectively enrolled, all patients had received GDMT for at least three months but the LVEF remained below 55%. Parameters of transthoracic echocardiography (TTE) at baseline, during GDMT, and after RDN were compared to analyze whether RDN can further improve the LVEF of patients on the basis of GDMT. Results A total of 7 HF patients diagnosed with DCM were enrolled, the mean age was (52.86±9.86) years old, and 5(71.4%) were male. After an average of (9.29±8.06) months of GDMT, LVEF significantly increased from baseline (34.86%±10.22%) to (44.57%±5.59%, P=0.024).Three months after RDN, LVEF was further significantly improved (54.43%±9.05%, P=0.026). The average follow-up after RDN was (11.00±4.12) months. The LVEF remained stable (54.86%±7.10%, P=0.805), and no adverse events occurred in the patients. Conclusions RDN can further enhance the LVEF of HF patients on the basis of GDMT.

Objective: To establish a progressive research strategy for “colonic components analysis - efficacy verification and mechanism exploration - gut microbiota”, screen pharmacodynamic substances, and investigate their mechanism via gut microbiota. Methods: The pharmacodynamics of Gegen Qinlian decoction (GQD) were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis (UC). Ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC. To analyze the structure and function of characteristic genera of GQD and its active components, 16S rRNA sequencing was performed. Results: We identified 67 prototypic and 14 metabolic components of GQD in the UC colon. The primary prototype components are flavonoids and alkaloids, including puerarin (PUE), baicalin (BAI), and berberine (BER). The metabolism was predominantly sulfonation. Efficacy verification showed that the main active components, puerarin, baicalin, and berberine, had good therapeutic effects on UC. The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota. The abundance of gut microbiota involved in the metabolism of the prototype components was influenced by the corresponding components. The function prediction results showed that PUE was the most comparable to GQD, with 24 consistent pathways. BAI and BER showed comparable gut microbiota regulation pathways. Characteristic pathways of BER include glucometabolic processes. Conclusion This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components. This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC, as well as changes in the structure and function of the gut microbiota, clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.

Objective:To investigate the risk factors for esophageal varices in patients with liver cirrhosis,to establish a predictive model,and to provide reasonable guidance for the prevention of early esophageal varices in patients with liver cirrhosis.Methods:A retrospective analysis was performed for 1 113 patients with liver cirrhosis who attended the hospitals in Chongqing,China from Decem-ber 2006 to May 2021.Recursive feature elimination(RFE)and four machine learning methods were used for the screening of features,and five machine learning predictive models were established by logistic regression,random forest,support vector machine(SVM),de-cision tree,and eXtreme Gradient Boosting(XGBoost).The receiver operating characteristic(ROC)curve was used to evaluate the per-formance of each model,and the model with the best performance was used to investigate the risk factors for esophageal varices in pa-tients with liver cirrhosis.SHAP plots were used to explain the impact of each risk factor on patients.Results:The XGBoost model showed the best performance in predicting the risk of esophageal varices in patients with liver cirrhosis,with an area under the ROC curve of 0.872(95%CI=0.813-0.918).SHAP plots showed that platelet count,diameter of the portal vein,cholinesterase,albumin,ala-nine aminotransferase,hemoglobin,prothrombin ratio,prothrombin time,and serum total protein were risk factors for esophageal vari-ces in patients with liver cirrhosis.Conclusion:This study shows that the XGBoost predictive model has a relatively high predictive value,and the risk factors obtained by this model have a certain guiding significance for the clinical prevention and treatment of early esophageal varices in patients with liver cirrhosis.

Objective:To investigate the hepatoprotective effect of N-acetylcysteine(NAC)on rats with liver injury induced by cisplatin and its effect on intestinal flora and the expression of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and nuclear factor-kappa B(NF-κB).Methods:Male Sprague-Dawley rats were randomly divided into control group(CG),cisplatin group(CP),and NAC group.The rats in the NAC group were given NAC 15 mg/kg by gavage for 8 consecutive days.At half an hour after intragastric administration on the fifth day,all rats except those in the NC group were given intraperitoneal injection of 8 mg/kg cisplatin to induce acute liver injury.An automatic biochemical analyzer was used to measure the content of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),and total bilirubin(TBIL);liver index was calculated for the rats;Western blot was used to measure the relative expression levels of NF-κB,IL-6,and TNF-α in liver tissue;the 16S rDNA technique was used to measure and analyze the amplification information of the V3-V4 regions of each sample.Results:Compared with the NC group,the CP group had significant increases in the content of AST,ALT,ALP,and TBIL,while NAC reversed the abnormal liver function caused by cisplatin.Compared with the NC group,the CP group had a sig-nificant increase in liver index(P=0.000),while the NAC group had a significant reduction in liver index compared with the CP group(P=0.007).Compared with the NC group,the CP group had signifi-cant increases in the expression levels of IL-6,TNF-α,and NF-κB,while the NAC group showed reductions in the expression of these genes,with significant differences in the expression of IL-6 and TNF-α(P=0.006 and 0.000).Compared with the NC group,the CP group had a significant increase in the α-diversity index of intesti-nal flora,while compared with the CP group,the NAC group tended to have a reduction in the α-diversity index of intestinal flora.Com-pared with the CP group at the phylum level,the NAC group had an increase in the abundance of Actinobacteria and a reduction in the abundance of Firmicutes.Compared with the CP group at the genus level,the NAC group had a reduction in the abundance of Rumino-coccaceae and increases in the abundance of Bifidobacterium and Allobaculum.Conclusion:NAC can alleviate acute liver injury caused by cisplatin,possibly by downregulating the expression of IL-6,TNF-α,and NF-κB and regulating the abundance and diver-sity of intestinal flora.

Objective To systematic analyze the risk factors for new-onset urethral stricture after transurethral holmium laser enucleation of the prostate(HoLEP)in the treatment of benign prostatic hyperplasia(BPH).Methods A case-control study was conducted on 746 BPH patients undergoing HoLEP treatment in Department of Urology of the Third Medical Center of Chinese PLA General Hospital from November 2021 to August 2024.After 23 cases were excluded because of complication of prostate cancer,finally 723 patients were included.General clinical data such as age,height,weight,history of smoking and drinking,perioperative parameters,and follow-up data at 1,3 and 6 months after operation were collected.Univariate and multivariate logistic regression analyses were used to identify the clinical risk factors for new-onset urethral stricture after HoLEP.Results The subjected patients had a median age of 66.5(64.0,75.0)years,and a preoperative median prostate volume of 66(45,92)mL,and a median indwelling catheter time of 4(4,5)d.The incidence of new urethral stricture after operation was 5.8%(42/723),with membranous part of the urethra(61.9%)the most common site,followed by the external urethral orifice(21.4%)and the bladder neck(7.1%).Risk factor analysis indicated that low BMI(<18.5 kg/m2)(OR=4.682,P=0.037),young age(OR=0.946,P=0.005),and postoperative urinary tract infection(OR=4.513,P=0.001)were independent risk factors for new-onset urethral stricture after surgery.Prostate volume and indwelling time of urinary catheter had no significant association with the occurrence of new urethral stricture after surgery.Conclusion The occurrence of new-onset urethral stricture after HoLEP is significantly correlated with BMI,age and urinary tract infection.The above 3 factors can be used as better predictors of new-onset urethral stricture after HoLEP.

Objective To explore the role and mechanism of mechanically sensitive ion channel Piezo2 in mechanical allodynia of rats with low back pain induced by simulating the low-frequency vibration of a helicopter.Methods Low-frequency vibration(LFV)model with 3-dimensional 6 degrees of freedom was used to induce low back pain in awake rats in a sitting position.Twenty-four male SD rats(8 weeks old)were randomly divided into control(Ctrl)group and LFV group.HE staining was used to evaluate the injury of the multifidus muscle.Von Frey test was carried out to detect pain sensitivity.Open field test was employed to assess the spontaneous activity and anxiety.ELISA,Western blotting and immunofluorescence staining were performed to detect the expression of NGF,TrkA and downstream molecule Piezo2.Dorsal root ganglia(DRG)neurons was isolated from SD rats and primarily cultured.After identified with immunofluorescence staining,the neurons were divided into the Ctrl group,the LFV group,and the LFV+D-GsMTx4(D-G4,an Piezo2 channel antagonist)group.Western blotting was used to detect the protein expression of Piezo2,and a calcium ion fluorescent probe was utilized to detect the intracellular Ca2+.The DRG neurons were pretreated with 50 ng/mL NGF for 1 h.Calcium ion fluorescent probe was used to observe the changes in intracellular Ca2+in the LFV group,the LFV+NGF group,and the LFV+NGF+D-G4 group.Results The rats of the LFV group showed abnormal morphology in multifidus muscles,accompanied with inflammatory cell infiltration,decreased paw withdrawal reflex threshold(P<0.05),and shortened total active time and active time in the centre,and decreased distance traveled in the centre(P<0.05),while prolonged total stationary time,stationary time in the periphery,and increased distance traveled in the periphery(P<0.05),and moreover,enhanced expression of Piezo2,NGF and TrkA in the DRG tissues(P<0.05).Cell experiments showed that compared with the Ctrl group,the expression of Piezo2 in the neurons was increased(P<0.05),and the intracellular Ca2+level was significantly elevated in the LFV group(P<0.05).Compared with the LFV group,the Ca2+level was higher in the LFV+NGF group(P<0.05),and the sensitization effect of NGF on Piezo2 was reversed after D-G4 treatment(P<0.05).Conclusion Sustained low-frequency vibration induces low back pain and mechanical allodynia in rats through the NGF-TrkA/Piezo2 pathway.