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.

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 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.

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: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.

Objective:To investigate the dynamic changes of routine laboratory parameters during the course of hemorrhagic fever with renal syndrome (HFRS) and estimate the predictive value for the severity of the disease.Methods:A retrospective cohort study was conducted, which enrolled 394 HFRS patients admitted to the Second Affiliated Hospital of Air Force Medical University (374 cases) and the Second Affiliated Hospital of Xi′an Jiaotong University (20 cases) from January 2019 to January 2022. The patients were divided into mild (mild and moderate) and severe (severe and critical) groups.The basic information, personal history, past history, treatment, complications and other clinical data of patients were collected and the results of the laboratory examinations in the morning at day 1, 2, 3, 4, 5, 7, 10, 15, 20 and 25 of hospitalization and before discharge were recorded. The dynamic changes of the patients′ routine laboratory indicators and the dynamic predictive values of each indicator for severe condition were analyzed. Mann-Whitney U test and chi-square test were used for comparison, and receiver operator characteristic (ROC) curve was used for predictive value evaluation. Results:The age of 212 patients in the mild group was 38(27, 61) years, and that of 182 patients in the severe group was 49(32, 64) years, the difference was statistically significant ( Z=-2.24, P=0.025). The incidences of acute pancreatitis, acute respiratory distress syndrome, multiple organ dysfunction syndrome, the utilization rates of blood purification and mechanical ventilation in the severe group were 6.0%(11/182), 12.6%(23/182), 19.8%(36/182), 89.6%(163/182) and 22.5%(41/182), respectively, and those in the mild group were 0(0/212), 0(0/212), 0(0/212), 15.6%(33/212) and 0.5%(1/212) respectively, and the differences were all statistically significant ( χ2=13.18, 28.45, 46.15, 214.48 and 50.02, respectively, all P<0.05). The levels of white blood cell count, lymphocyte count, monocyte count and neutrophil count were all increased rapidly after onset and peaked at days 4 to 6 of illness, with the counts of 14.2(9.7, 20.7)×10 9/L, 4.2(2.3, 6.2)×10 9/L, 1.5 (0.8, 3.3)×10 9/L and 8.3(4.3, 11.4)×10 9/L, respectively. Aspartate aminotransferase peaked (102(66, 178) U/L) within three days after onset and then decreased rapidly, returned to normal level by day 12. Blood urea nitrogen and creatinine both increased steadily after onset, peaked at day 9 to 10, with the levels of 13.2(7.7, 19.1) mmol/L and 255.4(122.9, 400.9) μmol/L, respectively. Prothrombin time, activated partial thromboplastin time, fibrinogen degradation products and D-dimer levels at day 3 after onset were 12.7(12.0, 13.2) s, 38.7(33.5, 51.9) s, 12.6(6.9, 32.0) mg/L and 4.9(2.2, 13.7) mg/L, respectively.Platelet count at day 4, neutrophil count at day 5, creatinine at day 11 and blood urea nitrogen at day 14 after onset had decent predictive values for estimating severity, of which the area under curve (AUC) values were 0.801(95% confidence interval (95% CI) 0.727 to 0.875), 0.824(95% CI 0.770 to 0.878), 0.862(95% CI 0.805 to 0.919) and 0.810(95% CI 0.722 to 0.897), respectively. Conclusions:Routine blood count, liver function and coagulation are important reference indicators for early warning of severe disease of HFRS, while with the progress of the disease, renal function indicators are effective in differentiating the severity of the disease. The platelet count at day 4, neutrophil count at day 5, creatinine at day 11 and blood urea nitrogen at day 14 after onset have predictive values for severe HFRS.

Objective:To analyze the clinical characteristics and risk factors for severe disease of hemorrhagic fever with renal syndrome (HFRS) in underage patients, and to construct the severe disease risk model.Methods:A total of 170 HFRS patients (<18 years old) from the Second Affiliated Hospital of Air Force Medical University (153 cases) and the Second Affiliated Hospital of Xi′an Jiaotong University (17 cases) from January 2009 to December 2021 were included. According to the severity of the disease, the patients were divided into mild and severe groups. Baseline demographic data, symptoms, signs, laboratory examination on admission and prognosis were analyzed between the two groups. Statistical comparisons were performed using the Mann-Whitney U test and chi-square test.Binary logistic regression was used to analyze the independent risk factors of patients with severe disease, and the severe disease risk model was built.The receiver operator characteristic curve was used to analyze the value of the risk model in predicting severity of disease. Results:Among the 170 underage patients, 132 (77.6%) were males, aged (14.9±3.1) years, including 124 cases in mild group and 46 cases in severe group. One hundred and sixty-nine cases (99.4%) had fever, 119 cases (70.0%) had headache, 106 cases (62.4%) had lumbago, 158 cases (92.9%) had skin and mucous congestion, and 101 cases (59.4%) had nausea and vomiting. Renal percussive pain was found in 139(81.8%) patients. The incidence of nausea and vomiting and bleeding of skin and mucosa in the severe group were 71.7%(33/46) and 67.4%(31/46), respectively, which were both higher than those in the mild group (54.8%(68/124) and 44.4%(55/124), respectively), and the differences were statistically significant ( χ2=3.97 and 7.12, respectively, both P<0.05). There were significant differences in platelet count, activated partial thromboplastin time (APTT), serum creatinine (SCr), aspartate aminotransferase, alanine aminotransferase, leukocyte count, total bilirubin and albumin levels between the two groups ( Z=-4.14, -4.04, -4.87, -3.90, -4.07, -2.60, -2.78 and t=2.50, respectively, all P<0.05). Binary logistic regression analysis showed that chemosis (odds ratio ( OR)=8.035, 95% confidence interval (95% CI) 2.946 to 21.916), SCr ( OR=1.010, 95% CI 1.006 to 1.015) and APTT ( OR=1.049, 95% CI 1.003 to 1.098) were the independent risk factors for severe HFRS in the underage patients. The risk model was constructed as: Logit(P)=-10.323+ 2.084×chemosis (no=0, grade Ⅰ=1, grade Ⅱ=2, grade Ⅲ=3)+ 0.010×SCr (μmol/L)+ 0.048×APTT (s). The area under the curve to predict severity of disease in underage HFRS patients was 0.868, with an optimal cut-off value of -4.39, with a sensitivity of 73.90% and a specificity of 91.10%. According to the internal verification of the data of the study based on the severe disease risk model, 34 out of 46 patients with severe disease were severe (sensitivity, 73.91%), 113 out of 124 patients with mild disease were mild (specificity, 91.13%). Conclusions:The clinical manifestations of the underage HFRS patients are not typical.The main manifestations are fever, headache and lumbago, nausea and vomiting, and the incidences of skin and mucous congestion and renal percussive pain are high.Chemosis, SCr and APTT are independent risk factors for severe disease in underage patients with HFRS. The severe disease risk model could effectively predict the severity of disease.

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 explore the risk factors of seroma after laparoscopic totally extraperitoneal hernia repair.Methods:The clinical data of 236 patients underwent laparoscopic totally extraperitoneal hernia repair from July 2018 to June 2021 in Jiaozhou Central Hospital of Qingdao City were retrospectively analyzed. The related risk factors of seroma after laparoscopic totally extraperitoneal hernia repair were analyzed.Results:Among 236 patients, the seroma occurred in 36 cases (seroma group), the incidence of seroma was 15.25%; no seroma occurred in 200 cases (non-seroma group). There were statistical differences in the duration of disease ≥5 years, scrotal hernia, internal inguinal ring defect ≥3 cm, rupture of hernia sac, experience of operators <5 years between 2 groups ( P<0.01 or <0.05); there were no statistical difference in age, body mass, type of patch, preoperative complications (including diabetes, chronic obstructive pulmonary disease and cardiac cerebrovascular disease) and operative time between 2 groups ( P>0.05). Multivariate Logistic regression analysis result showed that the duration of disease ≥5 years, scrotal hernia, rupture of hernia sac and experience of operators<5 years were independent influencing factors of seroma after laparoscopic totally extraperitoneal hernia repair ( OR = 5.147, 5.006, 0.044 and 3.315; 95% CI 1.513 to 17.516, 1.845 to 13.583, 0.008 to 0.240 and 1.029 to 10.679; P<0.01 or<0.05). Conclusions:The duration of disease ≥5 years, scrotal hernia, rupture of hernia sac and experience of operators<5 years are independent influencing factors of seroma after laparoscopic totally extraperitoneal hernia repair, and preoperative assessment of risk factors is helpful to reduce the incidence of seroma.

Objective     To introduce the application of transcatheter closure of multi-fenestrated atrial septal defect (ASD) via femoral vein under ultrasound guidance with amplatzer cribriform occluder (ACO) and atrial septal defect occluder (ASDO), as well as to assess its feasibility, effectiveness and safety. Methods     The clinical data of 48 patients with fenestrated ASD occluded via femoral vein under ultrasound guidance from December 2015 to May 2018 in our hospital were retrospectively analyzed, including 17 males and 31 females, aged 10 months to 51 years, an average of 11.50±13.86 years, and weighting 6-79 (27.00±20.14) kg. Among 48 patients with fenestrated ASD, 12 patients had double-foramen and 13 atrial septal aneurysm combined with defects and 23 multi-foramen. All patients underwent transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE) to complete the closure of fenestrated ASD. Ultrasound, electrocardiogram and chest X-ray were reviewed the next day after surgery to evaluate the curative effect. Results     Forty-eight patients with ASD were treated with 49 occluders, due to one patient with two occluders. There were 29 ASDO (8-26 mm) and 20 ACO (18-34 mm). During the operation, TTE/TEE examination showed that 48 patients were completely occluded, 13 patients showed fine bundle shunt in the unreleased push notification rod, and 9 patients had fine bundle shunt after the release of push notification rod. Fine bundle shunt was found in 8 patients 24 hours after operation, and microshunt was found in 3 patients 1 year after operation. All the patients were followed up. The occluder position was good. The right heart was reduced in different degrees, and the X-ray showed that the pulmonary blood was reduced in different degrees. No arrhythmia was found by electrocardiogram after operation. Conclusion     It is a safe and effective method to use ACO and ASDO to occlude ASD through femoral approach under ultrasound guidance.