Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Diabetic kidney disease(DKD)is one of the most important complications of diabetes.In recent years,domestic and foreign studies have found that mammalian target protein of rapamycin(mTOR)related signaling pathway is a classic pathway involved in the regulation of autophagy,which can achieve the therapeutic effect of DKD by targeting the autophagy pathway,and plays a crucial role in the prevention and treatment of DKD.In this paper,we reviewed the mechanism of mTOR-related signaling pathway targeted autophagy in the prevention and treatment of DKD,in order to provide a new reference and basis for clinical prevention and treatment of DKD.

Objective:To explore the clinical characteristics and risk factors of concurrent infection in adult patients with hypopituitarism (HP).Methods:Clinical data of patients diagnosed with HP in Fuyang People′s Hospital from October 2016 to August 2020 were collected. Patients were divided into infected group and non-infected group according to whether they were co-infected, and the differences in clinical characteristics between the two groups were compared. The risk factors of infection in HP patients were analyzed by binary logistic regression.Results:The top three clinical manifestations of 64 HP patients were decreased libido; lack of energy, fear of cold, and poor appetite; hyponatremia. Etiological analysis of 64 HP patients: 23 cases of Sheehan′s syndrome, 14 cases of postoperative brain tumors (pituitary adenoma, craniopharyngioma, meningioma), 8 cases of idiopathic, 7 cases of pituitary adenoma, 8 cases of pituitary volume and morphology changes, and 4 cases of empty sella turcica. 40.32%(25/62) of patients with adrenal axis dysfunction received glucocorticoid replacement therapy, with 80%(20/25) receiving prednisone and 20%(5/25) receiving hydrocortisone. The replacement dose was 2.5-25(6.77±3.90)mg of prednisone equivalent dose. 37.70%(23/61) of patients with low thyroid axis function received thyroid hormone replacement therapy, of which 52.17%(12/23) free thyroxine (FT4) levels were still lower than the lower normal limit. 20%(2/10) of males ≤60 years old and 5.56%(1/18) of females≤50 years old received hormone replacement therapy for patients with hypogonadism of the gonadal axis. Among 64 HP patients included, 29 were co-infected (infected group) and 35 were not co-infected (non infected group). There was no significant difference between the infected group and the non infected group in gender, etiology, number of pituitary axis involved, glucocorticoid replacement therapy dose, thyroid hormone replacement therapy dose, and sex hormone replacement therapy rate (all P>0.05). Compared with the non infected group, the infected group was older, had a longer course of disease, lower diastolic blood pressure (DBP) and albumin levels, with statistically significant difference (all P<0.05), while the other indicators showed no statistically significant difference (all P>0.05). The results of binary logistic regression analysis showed that age, course of disease, occupation, and albumin level were the influencing factors of HP complicated infection (all P<0.05). Conclusions:The most common cause of pituitary dysfunction in adults is Sheehan′s syndrome; Adult HP patients who are older, have a longer course of disease, work as farmers, and have hypoalbuminemia are more likely to develop concurrent infections.

Objective: To investigate the correlation between clinicopathological features and Miller/Payne (MP) grading system of breast carcinoma after neoadjuvant treatment and to establish novel prediction models. Methods: A total of 1 053 cases of invasive breast carcinoma NOS that undertaken neoadjuvant treatment according to Guidelines of CSCO for Breast Cancer were selected at the Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute from September 2016 to September 2019, and the clinical, pathologic data, MP grading and immunohistochemical staining were evaluated. Statistical analysis was conducted using R software. Several novel computer models on prediction of MP grading were established and validated. Results: Among 1 053 patients who accepted neoadjuvant treatment, 316 patients (316/1 053, 30%) were evaluated as MP5 postoperatively, and 737 patients (737/1 053, 70%) did not meet MP5 level. MP5 had significant association with histological grade, ER and PR expression, HER2 status, Ki-67 index and molecular classification (P<0.05). Univariate/multivariate logistic regression analyses further showed that the above clinicopathological features were also independent influencing factors of MP5 grade; five-fold cross-validation was used to evaluate the performance of the models, and the sensitivity and specificity of different models were obtained. Conclusions: MP grading of invasive breast carcinoma NOS after neoadjuvant treatment is associated with high histological grade, negative ER and PR expression, HER2 positivity, high Ki-67 index and molecular classification, which are independent influence factors. GBM model recommended through comparison can provide some help for clinical diagnosis and treatment.
Breast Neoplasms/pathology* ; Female ; Humans ; Ki-67 Antigen/metabolism* ; Neoadjuvant Therapy ; Neoplasm Grading ; Receptor, ErbB-2/metabolism* ; Receptors, Estrogen/metabolism* ; Receptors, Progesterone/metabolism*

Objective To investigate the value of the hepatocellular carcinoma (HCC) risk model REAL-B score in predicting the risk of HCC in chronic hepatitis B (CHB) patients receiving antiviral therapy in comparison with mPAGE-B, aMAP and PAGE-B scores. Methods A retrospective analysis was performed for the clinical data of 1160 CHB patients who received entecavir or tenofovir treatment for more than 1 year from January 2013 to December 2015 in Tianjin Second Peolple's Hospital, and the events of HCC were recorded. The area under the ROC curve (AUC) was used to evaluate the value of REAL-B, mPAGE-B, aMAP, and PAGE-B scores in predicting HCC. The Kaplan-Meier method was used to evaluate the cumulative incidence rate of HCC at different time points, and the log-rank test was used to compare the incidence rate of HCC between the groups with different scores. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. Results Among the 1160 CHB patients, 108 (9.8%) progressed to HCC within a median follow-up time of 5.3 (5.0-6.3) years. REAL-B score had an AUC of 0.848 (95% confidence interval [ CI ]: 0.816-0.880) in predicting the onset of HCC within 5 years, followed by aMAP score (AUC=0.823, 95% CI : 0.786-0.860), mPAGE-B score (AUC=0.822, 95% CI : 0.788-0.857), and PAGE-B scores (AUC=0.780, 95% CI : 0.736-0.824). The 5-year cumulative incidence rate of HCC was 0.8% in the low-risk group (with a REAL-B score of 0-3 points), which was significantly lower than the incidence rate of 11.8% in the medium-risk group (with a REAL-B score of 4-7 points) and 35.6% with the high-risk group (with a REAL-B score of 8-13 points) ( P < 0.05). In the low-risk group, REAL-B score had a negative predictive value of 100% and 99.67%, respectively, in predicting HCC within 3 and 5 years. Conclusion REAL-B score accurately predicts the risk of HCC in CHB patients receiving antiviral therapy, with a better predictive value than the other risk models within 3 years of antiviral therapy.

Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.

Objective To investigate the value of neutrophil-to-lymphocyte ratio (NLR), red blood cell distribution width-to-lymphocyte ratio (RLR), and lymphocyte-to-monocyte ratio (LMR) in predicting the prognosis of early small hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). Methods A retrospective analysis was performed for 132 patients newly diagnosed with early HCC who underwent RFA in Tianjin Second People's Hospital from September 2011 to December 2020. Preoperative data were collected and the patients were followed up to observe recurrence and overall survival (OS). The X-tile tool was used to determine the optimal cut-off values of NLR, RLR, and LMR based on 5-year survival rate and recurrence-free survival (RFS) rate, and then the patients were divided into N-R-L 0 group with 92 patients, N-R-L 1 group with 29 patients, and N-R-L 2 group with 11 patients. The chi-square test was used for comparison of categorical data between the three groups. The Kaplan-Meier method was used to plot the survival curve, and the log-rank test was used to compare RFS and OS rates between groups. The factors with statistical significance in the log-rank test were included in the multivariate Cox regression analysis to determine the risk factors for RFS and OS rates. Results There were significant differences in Child-Pugh class and albumin between the N-R-L 0, N-R-L 1, and N-R-L 2 groups ( χ 2 2=10.992 and 5.699, both P < 0.05). The 1-, 3-, and 5-year OS rates of the three groups were 100%/96.3%/90.7%, 96.6%/60.4%/41.3%, and 81.8%/46.8%/15.6%, respectively ( χ 2 =38.46, P < 0.000 1), and the 1-, 3-, and 5-year RFS rates of the three groups were 76.9%/52.5%/33.3%, 42.9%/13.1%/0, and 11.1%/0/0, respectively ( χ 2 =35.345, P < 0.000 1). The multivariate Cox regression analysis showed that tumor diameter ≥ 2 cm (hazard ratio[ HR ]=2.10, 95% confidence interval[ CI ]: 1.28-3.43, P =0.003; HR =3.67, 95% CI : 1.58-8.52, P =0.002), N-R-L score of 1 point ( HR =3.14, 95% CI : 1.81-5.46, P < 0.000 1; HR =8.27, 95% CI : 3.15-21.71, P < 0.000 1), and N-R-L score of 2 points ( HR =2.61, 95% CI : 1.06-6.42, P =0.037; HR =14.59, 95% CI : 3.96-53.78, P < 0.000 1) were independent predictive factors for RFS and OS. Conclusion N-R-L, a systemic inflammatory response marker composed of NLR, RLR, and LMR, is an independent risk factor for recurrence and survival of early small HCC after RFA, and it can be used as a useful noninvasive biomarker in combination with tumor features to predict the recurrence and survival of early HCC after RFA.

Aim To explore the mechanism of pediatric asthma based on network pharmacology and molecular docking technology. Methods Through TCMSP database, the chemical information and the targets of TCM chemical components and pediatric asthma targets in PubChem, SwissTargetPrediction and GeneCards were collected, and the intersection gene, namely the target gene of pediatric asthma was used. The “Drug-active ingredient-target” map was plotted with the Cytosacape 3.7.2 software. Protein interaction network maps were constructed based on the String database and analyzed by Cytoscape 3.7.2. GO and KEGG pathway analysis of acting targets using the Metascape database and bubbles were plotted on the Omicshare platform. Results A total of 238 active components and 11 corresponding 697 main targets were selected, 1 052 pediatric asthma disease target targets and 242 common targets were selected. Enrichment analysis found that common targets were primarily involved in biological processes such as MAPK cascade regulation and inflammatory response, as well as calcium signaling pathway, cAMP signaling pathway, AGE-RAGE signaling pathway, cGMP-PKG signaling pathway, etc. Molecular docking results showed that the active components of Astragalus(5'hydroxyiso-muronulatol-2',5'-di-O-Glucoside)docked well with the SRC, TP53, and IL-6 targets. We proved that anti-resistant drinking could down-regulate the expression of IL-6, SRC and TP53. Conclusions Gubenfangxiaoyin drinking may be involved in the regulation of the STAT3, SRC, AKT1, TP53, TNF, MAPK3, TP53,TNF,MAPK3 and IL6 and other targets, involved in the regulation of calcium-CAMP signaling pathway in childhood asthma, AGE-RAGE signaling pathway, cGMP-PKG signaling pathway, reduce the MAPK cascade, inflammatory response, etc, and play a role in the prevention and treatment of asthma.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Subcortical vascular mild cognitive impairment (svMCI) is a common prodromal stage of vascular dementia. Although mounting evidence has suggested abnormalities in several single brain network metrics, few studies have explored the consistency between functional and structural connectivity networks in svMCI. Here, we constructed such networks using resting-state fMRI for functional connectivity and diffusion tensor imaging for structural connectivity in 30 patients with svMCI and 30 normal controls. The functional networks were then parcellated into topological modules, corresponding to several well-defined functional domains. The coupling between the functional and structural networks was finally estimated and compared at the multiscale network level (whole brain and modular level). We found no significant intergroup differences in the functional–structural coupling within the whole brain; however, there was significantly increased functional–structural coupling within the dorsal attention module and decreased functional–structural coupling within the ventral attention module in the svMCI group. In addition, the svMCI patients demonstrated decreased intramodular connectivity strength in the visual, somatomotor, and dorsal attention modules as well as decreased intermodular connectivity strength between several modules in the functional network, mainly linking the visual, somatomotor, dorsal attention, ventral attention, and frontoparietal control modules. There was no significant correlation between the altered module-level functional–structural coupling and cognitive performance in patients with svMCI. These findings demonstrate for the first time that svMCI is reflected in a selective aberrant topological organization in multiscale brain networks and may improve our understanding of the pathophysiological mechanisms underlying svMCI.