Objective To study the relationship between serum insulin-like growth factor-1 (IGF-1) and resistin levels and osteoporosis in patients with type 2 diabetes mellitus (T2DM). Methods This study was conducted on 306 T2DM patients admitted to Baoding No.2 Central Hospital from January 2018 to January 2022. According to the detection results of bone mineral density, the patients were divided into osteoporosis group (T≤-2.5) and non-osteoporosis group (T>-2.5). The differences in IGF-1, resistin and bone mineral density were compared between the two groups. Pearson correlation analysis was used to analyze the correlation between serum IGF-1 and resistin levels and bone mineral density in patients with osteoporosis. Receiver operating characteristic (ROC) curve was applied to evaluate the application value of IGF-1 and resistin in predicting osteoporosis in patients with T2DM. Patients with T2DM complicated with osteoporosis were followed up for 2 years, and the occurrence of fractures was assessed. After univariate analysis, multivariate logistic regression analysis was applied to screen the risk factors for fractures in T2DM patients with osteoporosis. Results The incidence rate of osteoporosis in patients with T2DM was 53.59% (164/306). The IGF-1 level and bone mineral density level in the osteoporosis group were lower than those in the non-osteoporosis group, while the level of resistin was higher than that in the non-osteoporosis group (P<0.05). Serum IGF-1 in patients with osteoporosis was positively correlated with bone mineral density, and serum resistin was negatively correlated with bone mineral density (P<0.05). The AUC, sensitivity and specificity of combination of IGF-1 and resistin in predicting osteoporosis were 0.888, 82.93% and 62.68% respectively, which were all higher than those of single factor prediction (P<0.05). The 164 T2DM patients with osteoporosis were followed up for two years, and 15 patients developed fragility fractures, with the incidence of fracture of 9.15% (15/164). Multivariate analysis showed that hypoproteinemia, high-intensity exercise, lack of nutritional management, low IGF-1, and high resistin were risk factors for fractures in patients with T2DM complicated with osteoporosis (P<0.05). Conclusion For patients with T2DM, the incidence rates of osteoporosis and fractures are high. The levels of IGF-1 and resistin are closely related to bone mineral density, which can be combined to predict osteoporosis. Hypoproteinemia, high-intensity exercise, lack of nutritional management, low IGF-1 and high resistin are risk factors for fractures in T2DM patients with osteoporosis. It is necessary to carry out targeted preventive measures in clinical practice to reduce the incidence rate of fractures.

OBJECTIVE To compare the effects of leuprorelin and mifepristone on sex hormone levels， ovarian function， adverse reactions， and recurrence in patients with endometriosis （EMs） after surgery. METHODS A total of 178 patients who underwent surgical treatment for EMs in Ji’an Central People’s Hospital from September 2021 to September 2023 were randomly divided into the leuprorelin group and the mifepristone group， with 92 cases in each group. Medication was initiated on days 1 to 5 of the first menstrual cycle following surgery. Patients in the leuprorelin group received subcutaneous injections of Leuprorelin acetate microspheres， 3.75 mg per time， once every four weeks， for a total of 6 injections. Patients in the mifepristone group took 12.5 mg of Mifepristone capsules orally once daily for six consecutive months. Visual analog scale （VAS）， serum sex hormone levels [follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E2）]， ovarian function indicators [anti- Müllerian hormone （AMH）， antral follicle count （AFC）]， and T helper 1 cell （Th1）/Th2 shift markers [interferon-γ （IFN-γ）， interleukin 2 （IL-2）， IL-4， and IL-10] were compared between the two groups before surgery and after treatment. Incidence and outcome of adverse reactions and recurrence within one year were also compared between the two groups. RESULTS There were no statistically significant differences in baseline indicators between the two groups before surgery （P＞0.05）. After treatment， both groups showed significantly lower VAS scores for chronic pelvic pain， dysmenorrhea and dyspareunia， and significantly reduced serum FSH， LH， E2， IL-4 and IL-10 levels compared to before surgery （P＜0.05）， while serum IFN-γ and IL-2 levels were significantly increased （P＜0.05）； the leuprorelin group showed significantly greater improvements than the mifepristone group in all these indicators （P＜0.05）. After treatment， serum AMH levels in both groups were significantly lower than before surgery levels， while AFC was significantly increased （P＜0.05）； the leuprorelin group had significantly higher serum AMH levels and more AFC compared to the mifepristone group （P＜0.05）. There were no significant differences in the incidence of adverse reactions and outcome rates between the two groups （P＞0.05）. During one year of follow-up after discontinuation， the recurrence rate in the leuprorelin group was significantly lower than in the mifepristone group （1.15% vs. 10.99%， P＜0.05）. CONCLUSIONS Both leuprorelin and mifepristone are effective therapeutic drugs for EMs， but the former has advantages in alleviating pain， regulating serum sex hormone levels， protecting ovarian function， regulating immune function and reducing recurrence rates.

ObjectiveTo investigate the incidence rate of primary liver cancer （PLC） and the progression of liver fibrosis in chronic hepatitis B （CHB） patients with low-level viremia （LLV） （HBV DNA<2 000 IU/mL but ≥20 IU/mL） after treatment adjustment， and to provide more robust evidence for clinical practice. MethodsA retrospective analysis was performed for the clinical data of LLV patients who initially received nucleos（t）ide analogue （NAs） for at least 48 weeks at the Fifth Medical Center of PLA General Hospital from August 2007 to April 2017 and subsequently underwent NAs adjustment due to LLV， and according to the virologic response after 48 weeks of treatment adjustment， the patients were divided into LLV group and complete virological response （CVR） group （HBV DNA<20 IU/mL）. The patients were followed up once every 3‍ ‍—‍ ‍6 months till the primary endpoint event of PLC or October 2024. The incidence rate of PLC and the progression of liver fibrosis were observed， and the progression of liver fibrosis was defined as an increase of ≥1 grade in fibrosis-4 （FIB-4） index. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the cumulative incidence rate of PLC， and the Log-rank test was used for comparison between groups； the Cox regression analysis was used to investigate the risk factors for PLC， and the Logistic regression analysis was used to investigate the influencing factors for the progression of liver fibrosis. ResultsA total of 307 patients were enrolled， with a mean age of 50.0 years， and the male patients accounted for 80.5%. After 48 weeks of treatment with the adjusted NAs regimen， 254 patients （82.7%） achieved CVR， and 53 patients （17.3%） still had LLV. For the LLV group， the incidence rate of PLC was 30.2% and the rate of liver fibrosis progression was 22.6%， while for the CVR group， the incidence rate of PLC was only 13.4%， and the rate of liver fibrosis progression was 7.5%. The multivariate regression analyses showed that LLV was an independent risk factor for the onset of PLC （hazard ratio=2.623， 95% confidence interval ［CI］： 1.315‍ ‍—‍ ‍5.234， P=0.006） and the progression of liver fibrosis （odds ratio=3.213， 95%CI： 1.385‍ ‍—‍ ‍7.455， P=0.007）. ConclusionActive adjustment of treatment is needed immediately after the diagnosis of LLV to improve CVR， and if LLV persists after treatment adjustment， it is necessary to enhance the monitoring of liver fibrosis progression and PLC， so as to facilitate early diagnosis and treatment.

Objective To examine the significance of susceptible gene detection for hereditary cancer syndrome (HCS) among general population. Methods A total of 2 928 individuals undergoing routine health examinations in Healthcare Center of Zhongshan Hospital, Fudan University, from September 2021 to April 2024 were enrolled retrospectively. Next generation sequencing was employed to identify susceptible genes for HCS. American College of Medical Genetics and Genomics (ACMG) guideline was used to analyze the pathogenicity of variants. Clinical data, imagings, follow-up data were also collected. Results The overall mutation rate of HCS panel was 3.59% (105/2 928), with 0.61% (18/2 928) for MutY DNA glycosylase (MUTYH), 0.27% (8/2 928) for breast cancer susceptibility gene 1/2 (BRCA1/2) and 0.23% (7/2 928) for mismatch repair (MMR) genes. Conclusions Healthy individuals carrying tumor susceptible genes usually lack the relevant clinical phenotypes. Whether comprehensive testing needs to be carried out among healthy people remains to be further explored.

Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

ObjectiveTo investigate the features of liver histopathological damage in patients with indeterminate phase of chronic HBV infection， as well as the timing for initiating antiviral therapy in such patients. MethodsA retrospective screening was performed for the patients with chronic HBV infection who were hospitalized in The Fifth Medical Center of Chinese PLA General Hospital and underwent liver biopsy from March 2018 to April 2022， among whom the patients who met the criteria for indeterminate phase defined in Chinese guidelines for chronic hepatitis B prevention and treatment （2022 edition） were enrolled， and their clinical data were collected. Liver histopathological stage was determined using the Scheuer scoring system， with stages 0 — 4 for inflammation grade （G） and stages 0 — 4 for fibrosis degree （S）， and the patients were divided into groups based on the presence of significant necroinflammation （≥G2） and significant liver fibrosis （≥S2）. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A Spearman’s rank correlation analysis was used to investigate the correlation between liver histopathology and clinical factors， and the Logistic regression model was used to identify the independent influencing factors for significant necroinflammation and liver fibrosis. ResultsA total of 271 patients with indeterminate phase of chronic HBV infection were enrolled， among whom 61 （22.5%） had significant necroinflammation （≥G2） and 124 （45.8%） had significant liver fibrosis （≥S2）. The Logistic regression analysis showed that alanine aminotransferase ≥30 U/L （for male patients） or ≥19 U/L （for female patients） （odds ratio ［OR］=2.69， 95% confidence interval ［CI］： 1.39 — 5.21， P=0.003）， HBV DNA ≥2 000 IU/mL （OR=2.75， 95%CI： 1.38 — 5.48， P=0.004）， and liver stiffness measurement （LSM） ≥6.0 kPa （OR=4.57， 95%CI： 2.17 — 9.62， P<0.001） were independent risk factors for significant inflammation. HBV DNA ≥2 000 IU/mL （OR=1.82， 95%CI： 1.01 — 3.32， P=0.049） and LSM ≥6.0 kPa （OR=2.06， 95%CI： 1.23 — 3.43， P=0.006） were independent influencing factors for significant liver fibrosis. ConclusionAmong the patients with indeterminate phase of chronic HBV infection， a substantial proportion of patients have significant liver histopathological damage. Antiviral therapy should be initiated in a timely manner for patients with high-risk factors.

Objective To explore the correlation between the expression level of serum Receptor for Advanced Glycation End-Product(RAGE)and High-Mobility Group Protein B1(HMGB1)expression with the occurrence of acute respiratory distress syndrome(ARDS)and interferon-γ/interleukin-4(IFN-γ/IL-4)ratio in patients with severe pneumonia(SP).Methods A prospective investigation was carried out on one hundred children with SP admitted to our hospital from March 2020 to February 2022,and the participants were classified into ARDS group(n = 56)and control group(n = 44)based on the occurrence of secondary ARDS.General informations werec-ollected.The expression of RAGE,HMGB1,IFN-γ and IL-4 in peripheral blood was measured using Enzyme-Linked Immunosorbent Assay(ELISA).Then multivariate Logistic regression analysis was conducted to screen the influencing factors of secondary ARDS in SP children,and the correlation with IFN-γ/IL-4 ratio was verified by pearson correla-tion analysis,moreover,receiver operating characteristic(ROC)curve was plotted to evaluate the value of RAGE and HMGB1 expression in predicting the occurrence of ARDS in SP children.Results There were no statistical difference in gender,age,body temperature and onset season between the two SP groups.The ARDS group had more types of pathogenic bacteria,larger ratio of the partial pressure of oxygen in arterial blood to the inspired oxygen fraction(PaO2/FiO2),higher Acute Physiological Score(APS),and up-regulated expression of RAGE,HMGB1,IFN-γ and IL-4,as well as larger IFN-γ/IL-4 ratio than those of control group,with statistical difference(all P<0.05).Multivariate Logistic regression analysis revealed that pathogen type,PaO2/FiO2 ratio,RAGE,HMGB1,IFN-γ,IL-4 and IFN-γ/IL-4 were the influencing factors for the occurrence of ARDS in children with SP.Pearson correlation test denoted that the serum RAGE and HMGB1 expression levels of SP children were positively correlated with IFN-γ,IL-4 and IFN-γ/IL-4 ratio(P<0.05).ROC curve found that the AUC of serum RAGE and HMGB1 in predicting the occurrence of ARDS in SP children was 0.707 and 0.750,with a sensitivity of 73.2%and 64.3%,and a specificity of 68.2%and 77.3%.The combined test of RAGE and HMGB1 in predicting the occurrence of ARDS in SP children reached an AUC of 0.848,providing a sensitivity and specificity of 80.4%and 81.8%respectively.Conclusions Serum RAGE and HMGB1 expression levels are elevated in SP children with ARDS,and the two are positively correlated with IFN-γ/IL-4 ratio.Therefore,monitoring serum RAGE and HMGB1 expression in children with ARDS secondary to SP has predictive value for the risk of ARDS in SP children.

Lung cancer, one of the most prevalent cancer types globally, underscores the critical importance of early detection and precise diagnosis in its management. However, conventional pathological diagnostic methods encounter various limitations, including the intricacies of the diagnostic process and the challenges in achieving uniform results. In contrast to traditional pathology, digital pathology integrates digitized pathological information with artificial intelligence, and offers a pathway for rapid and accurate diagnostic assistance. It holds the potential to delve into the tumor characteristics and microenvironment information, thereby supporting precision diagnosis and treatment for lung cancer. This article elucidates the recent applications of digital pathology in lung cancer diagnosis, staging, treatment, and prognosis. Additionally, it addresses the challenges currently faced by digital pathology.

Objective:To analyze the emergency sample testing time of VITROS XT 3400 biochemical testing system and evaluate its testing method.Method:Retrospective analysis was conducted on all specimens from the emergency laboratory department of our hospital from August 2020 to July 2022, including albumin(Alb), total protein(TP), aspartate amino transferase(AST), alanine aminotransferase(ALT), creatinine (Cr), blood Urea Nitrogen(BUN), calcium (Ca) and glucose (Glu) to calculate the utilization rate of composite dry slide projects. A total of 635 serum samples were collected from emergency patients in our hospital from June 20 to 26, 2022, and the difference in sample testing time was compared between VITROS XT 3400 (composite dry tablets) group and VITROS 4600 (ordinary dry tablets) group during low and peak periods. The difference in replacement reagent and daily maintenance time was also compared between the two groups.Result:The pairing rates of three projects (Alb-TP, AST-ALT, Cr-BUN) are all over 99%. The detection time of the VITROS XT 3400 group samples was significantly shorter than that of the VITROS 4600 group [(945±477) s compared to (1 101±567) s, t=20.378, P<0.001]. The detection time of the VITROS XT 3400 group samples during high and low peak periods was significantly shorter than that of the VITROS 4600 group [low peak period ( n=322): (857±567) s compared to (905±528) s, t=13.102, P<0.001; peak period ( n=313): (1 035±400) s compared to (1 303±492) s, t=21.876, P<0.001], The reagent replacement time of the VITROS XT 3400 group was significantly shorter than that of the VITROS 4600 group [(690±127) s vs (869±152) s, t=11.470, P<0.001]. There was no statistically significant difference in daily maintenance time between the VITROS XT 3400 group and the VITROS 4600 group [(1 771±123) s vs (1 765±95) s, t=0.238, P=0.834]. Conclusion:XT 3400 has faster detection speed when using the composite dry slides, which can better alleviate the detection pressure during peak hours.