The treatment landscape for metastatic renal cell carcinoma(mRCC)has evolved rapidly over the past two decades with the introduction of targeted therapies and novel immune checkpoint inhibitors.Among these developments,cytoreductive nephrectomy(CN)remains a controversial and unresolved issue,with its survival benefits being questioned compared to systemic therapy(ST).The role and optimal timing of CN in the context of modern systemic treatment for mRCC remain unclear.Additionally,there is still no well-defined consensus on patient selection for CN.Therefore,this article provides a concise review of current evidence regarding CN in mRCC,incor-porating the latest renal cancer management guidelines.We focus particularly on optimal surgical timing,candidate patient selection,and the therapeutic value of metastasectomy.Furthermore,we examine the current role of CN in metastatic non-clear cell renal cell carcinoma and explore its evolving clinical applications and future prospects in mRCC treatment.

In recent years, studies have found that the abnormal expression of rhythm genes is closely related to the risk of occurrence and the progression of the disease course of colorectal cancer. In addition, chronotherapy based on the circadian rhythm theory has shown certain effects in the clinical treatment of colorectal cancer, but there are still great limitations. Therefore, it is very important to clarify the mechanism of action of rhythm genes in the occurrence and development of colorectal cancer, which may provide a theoretical basis for the clinical application of chronotherapy.

The treatment landscape for metastatic renal cell carcinoma(mRCC)has evolved rapidly over the past two decades with the introduction of targeted therapies and novel immune checkpoint inhibitors.Among these developments,cytoreductive nephrectomy(CN)remains a controversial and unresolved issue,with its survival benefits being questioned compared to systemic therapy(ST).The role and optimal timing of CN in the context of modern systemic treatment for mRCC remain unclear.Additionally,there is still no well-defined consensus on patient selection for CN.Therefore,this article provides a concise review of current evidence regarding CN in mRCC,incor-porating the latest renal cancer management guidelines.We focus particularly on optimal surgical timing,candidate patient selection,and the therapeutic value of metastasectomy.Furthermore,we examine the current role of CN in metastatic non-clear cell renal cell carcinoma and explore its evolving clinical applications and future prospects in mRCC treatment.

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF） and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1， 2010 to December 31， 2021， and according to the drug susceptibility results， the patients were divided into multidrug-resistant （MDR） bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic （ROC） curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection， sputum （27.7%） was the most common specimen for detection， followed by blood （24.6%）， urine （18.5%）， and ascites （17.7%）. Bacterial infections were dominated by Gram-negative bacteria （58.5%）. Of all bacteria， Escherichia coli （18.5%）， Klebsiella pneumoniae （14.6%）， and Enterococcus faecium （13.8%） were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin （72.2%）， penicillin （57.4%）， ampicillin （55.6%）， and ciprofloxacin （53.7%）， while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin （73.3%）， cefazolin （50.0%）， and cefepime （47.4%）. The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection （61.5%）. Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection， the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase （Z=2.089， P=0.037）， aspartate aminotransferase （Z=2.063， P=0.039）， white blood cell count （Z=2.207， P=0.027）， and monocyte count （Z=4.413， P<0.001）. The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection （odds ratio=7.120， 95% confidence interval ［CI］： 2.478‍ ‍—‍ ‍20.456，P<0.001） and had an area under the ROC curve of 0.686 （95%CI： 0.597‍ ‍—‍ ‍0.776） in predicting ACLF with MDR bacterial infection（P<0.001）， with the optimal cut-off value of 0.50×10⁹/L， a sensitivity of 0.725， and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria， with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.

Objective This study was performed to establish and compare guinea pig models of tuberculosis using intranasal and aerosol infection routes at different doses.The overall goal was to provide a foundation for establishing a standardized guinea pig model of tuberculosis for the study of respiratory tract infection.Methods Twenty-four female guinea pigs were randomly divided into six groups of four guinea pigs each.They were then infected with two doses of Mycobacterium tuberculosis through either the aerosol route(groups A,B,and C)or intranasal route(groups D,E,and F).Aerosol infection groups consist of 3 groups:group A(Aerosol control group,uninfected control group),group B(Aerosol low-dose group,5×102 CFU),and group C(Aerosol high-dose group,5×103 CFU)Intranasal infection groups also consist of 3 groups:group D(Intranasal control group,uninfected control group),group E(Intranasal low-dose group,1×104 CFU),and group F(Intranasal high-dose group,5×104 CFU).The clinical manifestations of the guinea pigs were observed after infection.All guinea pigs were euthanized on day 14.Lung,spleen,and liver tissues were obtained for gross examination and histopathological analysis using hematoxylin-eosin staining to identify characteristic lesions associated with tuberculosis.Acid-fast staining was performed on in situ tissues and organs followed by bacterial culture to analyze the bacterial load.Results The guinea pigs in four infection groups(B,C,E,and F)exhibited macroscopic tuberculosis lesions in the lung,spleen,and liver.Histopathological examination revealed the presence of tuberculous granuloma lesions.Acid-fast staining and bacterial load analysis demonstrated that the bacteria were primarily localized in the lung tissue of aerosol-infected groups B and C,with a few also present in the spleen and liver,and the bacterial load was 104～105 CFU/mL.In intranasal infection groups E and F,bacteria were found in the lung,spleen,and liver with a similar bacterial load of 104～105 CFU/mL.There was no significant difference in lesion severity or bacterial load among groups B,C,E,and F;however,groups B,C,and F showed low standard deviations for both pathology and etiology.Conclusions A guinea pig model of acute tuberculosis was successfully established using two doses administered through distinct routes of infection.Pathological examination and pathogenic analysis demonstrated that an aerosol dose of 5×102 CFU of Mtb effectively established a homogeneous model of acute tuberculosis with good consistency among the animals.Additionally,intranasal infection with 5×104 CFU of Mtb produced a relatively uniform model of tuberculosis.Notably,however,aerosol infection at 5×102 CFU progressed to an acute tuberculosis model more rapidly than intranasal infection at 5×104 CFU.

Colorectal cancer is a common malignant tumor of the digestive system, with the characteristics of insidious onset, high risk of recurrence and metastasis, and poor prognosis. In recent years, clinical researches related to targeted therapy for colorectal cancer of different molecular subtypes such as RAS, BRAF, MMR/MSI, HER2, MET, NTRK, and POLE/POLD1 have all achieved certain results. Besides, the exploration of the combined application of molecular targeted therapy for colorectal cancer and other therapies is also continuously carried out. Clarifying the mechanism of action and clinical application progress of molecular targeted therapy for colorectal cancer can provide a more reliable basis for formulating clinical treatment plans for colorectal cancer patients.

Objective:To analyze the clinical characteristics of acute pancreatitis (AP) in Wuxi city based on multi center data from four tertiary hospitals.Methods:A retrospective analysis was conducted on the clinical data of 1 254 AP patients treated at Affiliated Hospital of Jiangnan University, Yixing People's Hospital, Jiangyin Hospital of Traditional Chinese Medicine, and Jiangyin People's Hospital from January 1, 2006 to December 30, 2009 and January 1, 2020 to December 30, 2023, including 743 males and 511 females, aged 53 (40, 67) years. The patients were divided into two groups based on the time period of inclusion: the 2006-2009 group ( n=456) and the 2020-2023 group ( n=798). Clinical data such as general clinical characteristics, etiology, laboratory parameters, imaging parameters, complications and prognosis were collected. Results:Compared with the 2006-2009 group, the 2020-2023 group had an increased proportion of biliary AP [60.6%(484/798) vs. 46.5%(212/456)], hyperlipidemic AP [11.2%(89/798) vs. 4.2%(19/456)], comorbid diabetes mellitus [22.1%(176/798) vs. 7.2%(33/456)], and hypertension [32.1% (256/798) vs. 13.6%(62/456)], all of which were statistically significant (all P<0.05). Compared with the 2006-2009 group, the interval between symptom onset and admission to the hospital became longer in the 2020-2023 group [2.0(1.0, 4.0)d vs. 1.0(0.5, 3.0)d], the length of hospitalization was shorter [10(8, 13)d vs.13(8, 19)d], and the proportion of the number of people who got better was increased [85.6%(683/798) vs. 56.4%(257/456)] but the proportion of the number of people who were cured was decreased [12.2%(97/798) vs. 39.7%(181/456)], and the proportion of patients with postoperative complications of ketoacidosis increased [1.90%(15/798) vs. 0.22%(1/456)], with the differences statistically significant (all P<0.05). In both groups, the season with the highest number of AP cases was spring. Conclusion:The incidence of biliary AP in Wuxi City is on the rise, hypertension, meanwhile diabetes mellitus and hyperlipidemia emerge as the predominant etiologic factors, and spring is the high incidence season of AP.

Objective:To analyze the clinical characteristics of acute pancreatitis (AP) in Wuxi city based on multi center data from four tertiary hospitals.Methods:A retrospective analysis was conducted on the clinical data of 1 254 AP patients treated at Affiliated Hospital of Jiangnan University, Yixing People's Hospital, Jiangyin Hospital of Traditional Chinese Medicine, and Jiangyin People's Hospital from January 1, 2006 to December 30, 2009 and January 1, 2020 to December 30, 2023, including 743 males and 511 females, aged 53 (40, 67) years. The patients were divided into two groups based on the time period of inclusion: the 2006-2009 group ( n=456) and the 2020-2023 group ( n=798). Clinical data such as general clinical characteristics, etiology, laboratory parameters, imaging parameters, complications and prognosis were collected. Results:Compared with the 2006-2009 group, the 2020-2023 group had an increased proportion of biliary AP [60.6%(484/798) vs. 46.5%(212/456)], hyperlipidemic AP [11.2%(89/798) vs. 4.2%(19/456)], comorbid diabetes mellitus [22.1%(176/798) vs. 7.2%(33/456)], and hypertension [32.1% (256/798) vs. 13.6%(62/456)], all of which were statistically significant (all P<0.05). Compared with the 2006-2009 group, the interval between symptom onset and admission to the hospital became longer in the 2020-2023 group [2.0(1.0, 4.0)d vs. 1.0(0.5, 3.0)d], the length of hospitalization was shorter [10(8, 13)d vs.13(8, 19)d], and the proportion of the number of people who got better was increased [85.6%(683/798) vs. 56.4%(257/456)] but the proportion of the number of people who were cured was decreased [12.2%(97/798) vs. 39.7%(181/456)], and the proportion of patients with postoperative complications of ketoacidosis increased [1.90%(15/798) vs. 0.22%(1/456)], with the differences statistically significant (all P<0.05). In both groups, the season with the highest number of AP cases was spring. Conclusion:The incidence of biliary AP in Wuxi City is on the rise, hypertension, meanwhile diabetes mellitus and hyperlipidemia emerge as the predominant etiologic factors, and spring is the high incidence season of AP.

Bladder cancer (BC) is one of the most common malignancies of the urinary tract. Surgery combined with chemoradiotherapy is the mainstay of treatment, but BC is markedly heterogeneous, leading to unsatisfactory outcomes. Antibody-drug conjugate (ADC), a new type of targeted drug, has achieved remarkable results in the treatment of tumors by coupling a chemical junction with a highly cytotoxic small molecule, which can exert anti-tumor effects while avoiding the impacts on normal cells. To date, several ADCs have been used in the treatment of BC at home and abroad, and play an increasingly important role in the field of BC therapy. This article briefly introduces the mechanism of ADC, the current application of ADC in BC treatment, and the problems and challenges faced, hoping to provide reference for clinical work.

Objective:To analyze the clinical epidemiological characteristics and the prognostic risk factors of patients with hemorrhagic fever with renal syndrome (HFRS).Methods:A total of 2 245 HFRS patients who were admitted to the Second Affiliated Hospital of Air Force Medical University from September 2008 to December 2021 were enrolled. Clinical epidemiological data (including gender, age, onset season, onset region, case fatality rate, et al) of HFRS patients were analyzed. The clinical epidemiological characteristics of patients with HFRS in the 2008 to 2012, 2013 to 2017, and 2018 to 2021 groups were compared. Statistical comparisons were performed using chi-square test. The Bonferroni adjusted P-value method was used for pairwise comparisons between groups, and logistic regression analysis was used to screen and evaluate the risk factors associated with the prognosis of HFRS patients. Results:The age of 2 245 HFRS patients was (42.3±15.9) years old. Most of them were male (79.24%(1 779/2 245)), and the main incidence area was Xi′an City (69.53%(1 561/2 245)). There were 132 deaths with an overall case fatality rate of 5.88%. There were 1 088 patients (48.46%) from 2008 to 2012, 647 patients (28.82%) from 2013 to 2017, and 510 patients (22.72%) from 2018 to 2021, with a mortality rate of 7.17%(78/1 088), 5.10%(33/647) and 4.12%(21/510), respectively. From 2008 to 2021, both the number of HFRS cases and the case fatality rate had shown a fluctuating downward trend. There were significant differences in case fatality rate, age distribution, onset season, and onset region among patients in the different year groups ( χ2=6.84, 49.22, 83.47 and 19.29, respectively, all P<0.05). The results of pairwise comparisons showed that the proportion of patients aged >60 years in the 2018 to 2021 group (23.33%(119/510)) was higher than those in the 2008 to 2012 group (12.13%(132/1 088)) and the 2013 to 2017 group (12.36%(80/647)), and the differences were statistically significant (both P<0.05). The proportions of patients at large peak (October to December) were 62.35%(318/510) in the 2018 to 2021 group and 56.26%(364/647) in the 2013 to 2017 group, which were both lower than that in the 2008 to 2012 group (75.18%(818/1 088)), and the differences were both statistically significant (both P<0.05). The case fatality rate of patients aged >60 years was 9.67%(32/331), which was higher than those of patients aged <30 years (2.86%(16/559)) and patients aged 30 to 60 years (6.20%(84/1 355)), with statistically significant differences (both P<0.05). Univariate analysis showed that age 30 to 60 years, age >60 years, smoking, complicated with hypertension, hypotensive shock and hypoxemia were significantly correlated with the prognosis of HFRS patients (odds ratio ( OR)=2.243, 3.632, 1.484, 3.532, 79.422 and 143.955, respectively, all P<0.05). The results of multivariate logistic regression analysis indicated that complicated with hypertension ( OR=2.467, P=0.004), hypotensive shock ( OR=11.658, P=0.001), and hypoxemia ( OR=67.767, P<0.001) were the independent risk factors affecting the prognosis of HFRS patients. Conclusions:The prevalence of HFRS has shown new changing characteristics from 2008 to 2021. The numbers of HFRS patients and the case fatality rates show a downward trend, and the proportion of HFRS patients aged >60 years increases. Complicated with hypertension, hypotensive shock and development with hypoxemia are the independent risk factors for the prognosis of HFRS.