Objective To investigate the effects of Chaihuang Yishen Granules on renal fibrosis in unilateral ureteral obstruction (UUO) mice and its underlying mechanisms. Methods Twenty-four 8-week-old male C57BL/6 mice were randomly divided into control group, model group, and low and high dose groups of Chaihuang Yishen Granules (6 in each group). In control group, only right kidney ureter was exposed and dissected. In model group, the UUO animal model was established by UUO. In low and high dose groups, mice were administered intragastrically at doses of 3.8 and 7.6 g/kg of Chaihuang Yishen Granules respectively,following the model group's method to establish the UUO model. After 7 days, the mice were euthanized and renal samples were collected. HE and Masson staining were used to observe pathological changes and fibrosis degree of the kidneys in each group, Sirius red staining was used to observe collagen deposition. The expression levels of α-smooth muscle actin (α-SMA), fibronectin (FN), type Ⅰ collagen (Col-Ⅰ), glycogen synthase kinase 3β (GSK-3β), and β-catenin related proteins were detected using Western blotting. Changes in A33 and GSK-3β, β-catenin mRNA levels were measured by RT-PCR. Additionally, a normal transformed C3H mouse kidney-1 (TCMK1) was used as control (normal group); an in vitro fibrosis model was established using TCMK1 stimulated with Transforming Growth Factor‑β (TGF‑β); and an in vitro drug model was established using TCMK1 treated with serum containing Chaihuang Yishen Granules. A33 was overexpressed in TCMK1 cells using a transfection with an A33 overexpression plasmid, and changes in fibrosis-related indicators and the expression of A33 and GSK-3β, β-catenin mRNA were observed. Results RT-PCR results showed that, compared with control group, A33 level was significantly increased in model group, while it was significantly reduced in both low and high dose groups of Chaihuang Yishen Granules (P<0.05). Western blotting showed that the expression levels of fibrosis-related factors such as α-SMA, FN, Col-Ⅰ in model group were significantly higher than those in control group (P<0.05); while compared with model group, the expression levels of α-SMA, FN, Col-Ⅰ in low and high dose groups of Chaihuang Yishen Granules were significantly lower (P<0.05). HE, Masson, immunohistochemical staining results showed that model group had severe kidney structural damage, significant increase in collagen deposition, and significantly higher expression levels of GSK-3β and β-catenin proteins compared with those in control group (P<0.01). In contrast, low and high dose groups of Chaihuang Yishen Granules had good kidney structure, significant improvement in kidney damage and fibrosis, and significantly lower expression levels of GSK-3β and β-catenin proteins compared with those in model group (P<0.05). In vitro experiment results confirmed that, compared with normal group, A33 overexpression promoted the upregulation of fibrosis-related factors in TCMK1 cells, significantly increase the expression of downstream target genes GSK-3β and β-catenin mRNA in the Wnt/β-catenin signaling pathway (P<0.05), and A33 overexpression reversed the cellular fibrosis changes downregulated by the serum containing Chaihuang Yishen Granules (P<0.01). Conclusion Chaihuang Yishen Granules significantly improve renal fibrosis in UUO mice by downregulating the A33/Wnt/β-catenin signaling pathway, suggesting that A33 may be a potential therapeutic target for renal fibrosis.

Objective To investigate the role and underlying mechanisms of WD repeat domain 82 (WDR82) protein in the pathogenesis and progression of glioma. Methods We analyzed the expression level of WDR82 in glioma tissues using GEPIA and UALCAN databases and further assessed WDR82 protein expression in glioma and adjacent normal tissues through immunohistochemical staining. The correlation between WDR82 expression and the prognosis of glioma patient was evaluated using Kaplan-Meier plotter. Experiments were conducted on A172 and U251 cell lines, which were categorized into four groups: control group (transfected with 3 μg pcDNA3), shR-control group (transfected with 3 μg pSilencer 2.1-U6), pWDR82 group (transfected with 3 μg pWDR82), and shR-WDR82 group (transfected with 3 μg shR-WDR82). Post-transfection, we confirmed transfection efficiency at 48 hours using qRT-PCR and measured cell viability at the same time point with CCK-8 assay. Clone formation assay was employed to assess cell proliferation capacity after 14 days of transfection, while flow cytometry was utilized to analyze cell apoptosis after 48 hours of transfection. Additionally, Western blotting was conducted to determine the expression levels of proteins related to proliferation and Akt/mTOR signaling pathway after 48 hours of transfection. Finally, the effect of WDR82 on tumor growth in NOD-SCID mice was investigated using tumor carrying experiment in vivo. Results Analysis of WDR82 expression in glioma tissues using GEPIA and UALCAN databases, along with immunohistochemical staining, revealed significantly higher expression levels compared to normal and paracancerous tissues (P<0.05). Additionally, WDR82 expression was not associated with gender or age of patients (P>0.05). Kaplan-Meier plotter analysis indicated that elevated WDR82 expression correlated with a poor prognosis in glioma patients (log-rank P=0.029). Overexpression of WDR82 notably enhanced the proliferation and inhibited the apoptosis of A172 and U251 cells, and also significantly upregulated the expression of MKI67, BCL2, CCND1, p-Akt and p-mTOR in A172 and U251 cells (P<0.05). Conversely, WDR82 knockdown had the opposite effects, inhibiting cell proliferation, increasing apoptosis and downregulating the expression of MKI67, BCL2, CCND1, p-Akt and p-mTOR (P<0.05). WDR82 knockdown in U251 cells significantly inhibited tumor growth in NOD-SCID mice (P<0.05). Conclusion High expression of WDR82 promotes the proliferation of glioma cells and the growth of tumors in vivo by regulating the AKT/mTOR signaling pathway.

Objective To analyze the incidence and mortality of malignant tumors among the middle-aged and elderly population in Chengguan district of Lanzhou from 2011 to 2021, and to discuss the related risk factors. Methods Using the research data of REACTION in Lanzhou, an epidemiological survey was conducted through cluster sampling in three communities in Chengguan district of Lanzhou since April 2011. The target population was middle-aged and elderly residents over 40 years old. Two follow-up surveys were carried out in 2014-2016 and 2021 successively, and 6543 people with complete follow-up data were finally included. The incidence and mortality rates of malignant tumors were calculated, as well as their age standardized rates with reference to the age composition of Segi's world standard population. Multivariate Cox regression analysis was used to screen the risk factors affecting the incidence and mortality of malignant tumors. Results After an average follow-up of 10.6 years, 314 new cases of malignant tumors were found in middle-aged and elderly residents in Chengguan district of Lanzhou, with an incidence rate and age standardized incidence rate of 454.30/100 000 and 128.93/100 000, respectively. A total of 158 deaths were attributed to malignant tumors, with a mortality rate and age standardized rate of 228.41/100 000 and 607.9/100 000, respectively; The age standardized incidence rate and mortality rate of malignant tumors males were both higher than those females (P<0.05). During the follow-up period, the age standardized incidence rate of malignant tumors in the general population showed an significant upward trend (P<0.05), whereas the age standardized mortality rate gradually decreased after a brief increase (P<0.05). Lung cancer, colorectal cancer, gastric cancer, and liver cancer were the main types of malignant tumors ranking in the top five in terms of incidence and mortality by gender. Multivariate Cox regression results indicate that male, age ≥60 years old, college education level or above, smoking history, drinking history, having been hit by major stressful events, central obesity, hypertension, and coronary heart disease are risk factors for the onset or death of malignant tumors (HR>1). Married, with family size ≥4, frequent consumption of fresh fruit, frequent consumption of fresh vegetables, frequent consumption of grains and tubers are protective factors for the onset or death of malignant tumors (HR<1). Conclusion The incidence of malignant tumors among middle-aged and elderly people in Chengguan district of Lanzhou from 2011 to 2021 showed an increasing trend, while the overall mortality was decreasing. Our study indicates early cancer screening in elderly populations, maintaining a healthy lifestyle and strengthening the management of chronic diseases are crucial for the prevention and treatment of malignant tumors.

Objective To investigate the diagnostic value of CT radiomics features in pulmonary alveolar proteinosis (PAP). Methods The general data and clinical characteristics of 24 patients with PAP in the Chinese PLA General Hospital from November 2008 to August 2022 were retrospectively collected and analyzed. Another 53 patients with other diffuse lung diseases except for PAP during the same period served as control group. The differences in the 10 conventional CT signs (semantic features) and 107 radiomics features between the two groups were compared. All patients were randomly divided into the training group (n=53) and the validation group (n=24) at a ratio of 7:3. CT semantic feature model, radiomics model and combined model to diagnose PAP were constructed in training group, and the diagnostic efficacy of models was compared using the receiver operating characteristic (ROC) curve in validation group. Decision curve analysis (DCA) was used to assess the value of models for practical clinical application. Radscore was calculated for the model with the highest diagnostic efficacy. Results A total of 24 patients with pathologically confirmed PAP were enrolled, with a male to female ratio of 3:1 and an average age of (44.6±15.2) years. The main clinical symptoms of patients with PAP included shortness of breath, cough, sputum and chest tightness. Compared with control group, the incidence of pleural effusion in PAP group was significantly lower (P<0.05), while no significant differences were observed in other CT features (P>0.05). The areas under the curve (AUC) of the semantic feature model for diagnosing PAP in training and validation group were 0.590 and 0.594, respectively, and in validation group, the accuracy, sensitivity, and specificity for diagnosis of PAP were 0.188, 1.000, and 0.188, respectively. The AUCs of the radiomics model in training group and validation group were 0.845 and 0.867, respectively, and in validation group, the accuracy, sensitivity, and specificity were 0.641, 0.938, and 0.703, respectively. The AUCs of the combined model in training group and validation group were 0.850 and 0.883, respectively, and in validation group, the accuracy, sensitivity, and specificity were 0.688, 0.750, and 0.938, respectively. The AUCs of the radiomics model and the combined model were significantly greater than that of the semantic feature model, but there was no significant difference in the AUCs between the first two models. The decision curve analysis showed that both the radiomics model and the combined model had high application value for predicting PAP. Conclusion CT radiomics shows higher clinical value in the diagnosis of PAP compared with conventional CT features.

Objective To explore the efficacy and safety of modified meibomian gland massage combined with ultrasonic atomization and drug therapy for dry eye in high-altitude military personnel. Methods A total of 180 patients (360 eyes) with dry eye who were diagnosed and treated by the medical team of General Hospital of Central Theater Command of Chinese PLA from July to October 2022 in Linzhi, Tibet (average altitude of 3100 meters) were selected as the research subjects. Patients were divided into four block groups based on the course of the disease: <1 month, 1-3 months, 3-6 months, and ≥6 months, and each block group was randomly assigned to control group, traditional group and modified group by random number table method, with 60 cases in each group. Control group received routine treatment (artificial tear drops and atomization fumigation); on the basis of routine treatment, traditional group underwent traditional meibomian gland massage, and modified group underwent modified meibomian gland massage. After 3 months of treatment, the scores of symptoms and signs, total effective rate, duration of treatment and incidence of adverse events were compared among the 3 groups. Results In the intra-group comparison before and after treatment, except for control group's symptom scores difference which was not statistically significant (P>0.05), all other scores decreased significantly (P<0.05). In the inter-group comparison after treatment, the scores of both traditional group and modified group were significantly better than those of control group (P<0.05), but no significant difference was observed in symptom and sign scores between traditional and modified groups (P>0.05). Compared with control group, the total effective rates of traditional group and modified group both significantly increased (P<0.01), but there was no significant difference in total effective rate between traditional and modified groups (P>0.05). The treatment time in modified group was significantly longer than that in control group (P<0.05), but significantly shorter than that in traditional group (P<0.05). The incidence of adverse events was significantly lower in modified group than that in traditional group (P<0.001). Conclusion In high-altitude areas, modified meibomian gland massage combined with ultrasonic atomization and local drug therapy for dry eye is safe and effective, non-invasiveness and easy to perform, and suitable for promoting and application in military field training.

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease, and hip preservation surgery has high clinical value in the early stages of ONFH, especially for young and middle-aged patients. However, the repair of ONFH is heterogeneous, leading to inter-individual variations in the efficacy of hip preservation. Currently, the existing tissue-engineered scaffolds in the field of hip preservation are uncontrollable after implantation, making it difficult to achieve precise repair. Smart responsive materials have good biocompatibility and self-feedback capability. By combining them with therapeutic drugs to construct stimulus-responsive drug delivery systems, new possibilities are provided for the precise repair of ONFH. This paper reviews the research progress of smart responsive materials at home and abroad. Based on the response principles of various materials and the repair characteristics of ONFH, the application prospects of various smart responsive materials such as reactive oxygen species-responsive, fluid shear stress-responsive, and light/magnetic-responsive materials are discussed and prospected in the field of precise repair for ONFH, providing new ideas for the precise treatment of ONFH.

Objective To explore the clinicopathological characteristics, prognosis and influencing factors of different pathological subtypes of gastric signet ring cell carcinoma (GSRC). Methods A retrospective analysis was performed on the clinical data of 232 patients with GSRC collected from January 2016 to December 2018 in Lanzhou University Second Hospital. According to the WHO classification criteria for GSRC, the patients were divided into pure gastric signet-ring cell carcinoma (pGSRC, n=36) and mixed gastric signet-ring cell carcinoma (mGSRC, n=196). The follow-up as of September 30, 2022, the survival analysis was done using Kaplan-Meier method, the univariate and multivariate Cox regression were performed to analyze the risk factors affecting the prognosis of GSRC patients. Results The median survival time of pGSRC and mGSRC patients was 41.0(6.0-70.0) months and 24.0(2.0-74.0) months, respectively. Kaplan-Meier analysis showed that combination with diabetes, anemia, tumor diameter, nerve invasion, lymphovascular invasion, T stage, N stage, GSRC pathological subtype, CA125 and tumor diameter could affect the overall survival (OS) of patients with GSRC after radical gastrectomy (P<0.05), but Her-2, whether adjuvant chemotherapy or not and others elements had no significant effect on OS of GSRC patients after radical gastrectomy (P>0.05). Univariate Cox regression analysis showed that the combination with diabetes (P=0.031), anemia (P=0.028), tumor diameter >5 cm (P=0.009), nerve invasion (P=0.002), lymphovascular invasion (P=0.002), mGSRC pathological type (P=0.039), T₂-T₄ stage (P=0.001), N₁-N₄ stage (P=0.004), pTNM stage Ⅲ (P=0.044), the number of lymph node metastasis >30 (P=0.044) and CA125 positive (P=0.009) were related to the prognosis of patients with GSRC after radical gastrectomy. Multivariate Cox regression analysis showed that mGSRC pathological type (P=0.035), T₂-T₄ stage (P=0.003), CA125 positive (P=0.010) were independent risk factors for poor prognosis of patients with GSRC after radical gastrectomy. Conclusion Compared with pGSRC, patients with mGSRC at diagnosis have higher pTNM stages, more aggressive, and shorter median survival time. mGSRC pathological type, T₂-T₄ stage, and CA125 positive were all independent factors affecting the prognosis of patients with GSRC.

Non-small cell lung cancer ( NSCLC ) is one of the most prevalent and deadly malignant tumors in the world. In recent years, artificial intelligence (AI) in computed tomography (CT) has harnessed the power of big data to automatically extract and learn imaging features, thereby assisting radiologists in reducing the workload and missed diagnosis rate of pulmonary nodules. An ELISA kit for detecting seven lung cancer autoantibodies (p53, SOX2, PGP9.5, CAGE, MAGE-A1, GAGE7, and GBU4-5) has been clinically implemented in China, showing high specificity in the early screening of NSCLC. Additionally, other liquid biopsy techniques such as circulating tumor DNA (ctDNA) methylation markers are also continually being explored. However, existing methods for the early diagnosis of lung cancer all have their limitations, and optimizing their combination or establishing diagnostic models has become a trend. This review summarizes the research progress and value of the seven lung cancer autoantibodies and CT AI in the early diagnosis of NSCLC, with the aim of providing a reference for their combined use in the early diagnosis of lung cancer in Chinese population.

Objective To investigate risk factors for acute phase reaction (APR) induced by zoledronic acid (ZA) treatment in osteoporosis and its impact on treatment adherence and persistence. Methods A retrospective analysis was conducted using clinical data from 471 osteoporosis patients with a median age of 67 years, who received 5 mg ZA in the First Affiliated Hospital of Chongqing Medical University between January 2013 and January 2022. Patients were divided into two groups based on the occurrence of APR: APR group (n=79) and non-APR group (n=392). Univariate and multivariate logistic regression analyses were used to identify factors inducing APR. The treatment persistence of ZA was analyzed using Kaplan-Meier curves. In addition, treatment adherence was analyzed. Results The incidence of APR was 33.2% after the first ZA injection, and it gradually decreased with an increase in the number of infusions. The multivariate logistic regression analysis showed that the first infusion, no history of oral bisphosphonate use, and high blood phosphorus levels were independent risk factors for APR. Three-year treatment adherence and persistence in APR group were 53% and 44%, respectively, while in non-APR group, they were 52% and 42%, respectively. Kaplan-Meier analysis showed no statistically significant difference in the persistence of ZA between two groups (P>0.05). Conclusions APR is prone to occur during ZA treatment for osteoporosis, but it does not affect the adherence and persistence of ZA treatment. First use of ZA, no history of oral bisphosphonates, and high blood phosphorus levels are independent risk factors for APR.

Objective To investigate the effects of inhibiting KDM2A gene on the proliferation, invasion and migration of liver cancer cells and its possible regulatory mechanism. Methods Forty pairs of HCC tissues and their adjacent normal counterparts were collected from 2014 to 2017 in Tongji Hospital, Tongji Medical College Affiliated to Huazhong University of Science and Technology. Human liver cancer cell lines HepG2, Huh7, HCCLM3, MHCC-97H and normal liver cells LO2 were cultured in vitro. The mRNA and protein expression levels of KDM2A in HCC tissues and cells were detected by qRT-PCR and Western blotting. Huh7 cells were taken and set up as follows: (1) si-NC group (transfected with si-NC) and si-KDM2A group (transfected with si-KDM2A); (2) mimic-NC group (transfected with mimic-NC), miRNA-29a-3p mimic group (transfected with miRNA-29a-3p mimic), inhibitor-NC group (transfected with inhibitor-NC) and miRNA-29a-3p inhibitor group (transfected with miRNA-29a-3p inhibitor). The mRNA and protein expression levels of KDM2A were detected by qRT-PCR and Western blotting. The invasion and migration of cells were detected by Transwell, the proliferation of cells was detected by CCK-8 methods. The online databases TargetScan, miRDIP, miRWalk, Starbase and miRDB were used to predict the binding sites of KDM2A and miR-29a-3p. The KDM2A 3'-UTR (WT) or KDM2A 3'-UTR (MUT) report plasmid was co-transfected with NC-miRNA or miR-29a-3p mimics respectively for 48 h in 293T cells, and the luciferase activity was detected by the luciferase reporter gene detection system. Results Compared with adjacent normal counterparts, the relative mRNA and protein expression levels of KDM2A in HCC tissues increased significantly (P<0.05). Compared with LO2, the relative mRNA and protein expression levels of KDM2A in HepG2, Huh7, HCCLM3 and MHCC-97H increased significantly (P<0.05). Compared with si-NC group, the proliferation, invasion and migration of Huh7 cells in si-KDM2A group decreased significantly (P<0.05 or P<0.01). The analysis results of TargetScan, miRDIP, miRWalk, Starbase and miRDB showed that there were binding sites between KDM2A and miR-29a-3p. The results of the dual luciferase reporter assay showed that miR-29a-3p mimic significantly reduced KDM2A-MUT luciferase activity (P<0.01). After overexpression of miRNA-29a-3p, the relative mRNA and protein expression levels of KDM2A were decreased (P<0.01), the proliferation, invasion and migration abilities were decreased (P<0.05) in Huh7 cells. After inhibiting the expression of miRNA-29a-3p, the relative mRNA and protein expression levels of KDM2A were increased (P<0.05), the proliferation, invasion and migration abilities were enhanced (P<0.05) in Huh7 cells. Conclusion Inhibiting the expression of KDM2A can reduce the proliferation and migration ability of Huh7 cells. miR-29a-3p may be the upstream regulator of KDM2A and participate in the occurrence and development of hepatocellular carcinoma.