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.

Lu Dangshen, a traditional authentic medicinal material of Codonopsis Radix is mainly produced in Shangdang (Changzhi) area of Shanxi Province. Baitiao Dangshen is mainly produced in Gansu Province. Codonopsis Radix contains many kinds of components such as phenylpropanoids, polyalkynes, alkaloids, terpenes, fatty acids, flavonoids, and so on. At present, the effect of producing areas on its chemical compositions has not been systematically studied. This study analyzed the differences of metabolites among Codonopsis pilosula from different producing areas by UPLC-HRMS. PCA, OPLS-DA coupled with Thermo mzcloud online and local databases were used to compare the overall differences of metabolites among Codonopsis pilosula from different producing areas, and the chemical constituents were identified to further screen and find out the different metabolites and analyze the metabolic pathways by information retrieval in HMDB, PubChem, Chemspider and KEGG databases. The results showed that 72 differential metabolites were identified in this study. There were 15 kinds of up-regulated and 57 kinds of down-regulated metabolites of Lu Dangshen compared with Baitiao Dangshen. The top 30 metabolic pathways were analyzed by KEGG enrichment, and the most important metabolic pathways were phenylpropanoid biosynthesis, which was demonstrated that phenylpropanoid biosynthesis pathway and related intermediate metabolites could be used as the characteristics of distinguishing Lu Dangshen from different habitats of Codonopsis pilosula. The present study provided a basis for analyzing the influence of producing areas on the chemical components of Codonopsis pilosula and reasonably evaluating the quality of Codonopsis Radix, and also provided a new idea for expounding the authenticity of Lu Dangshen.

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

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.

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.

OBJECTIVES: To evaluate the accuracy and safety of measurements of transcutaneous carbon dioxide partial pressure (TcPCO METHODS: A total of 45 very low birth weight infants were enrolled. TcPCO RESULTS: There was no significant difference in TcPCO CONCLUSIONS Lower electrode temperatures (38-41℃) can accurately measure blood carbon dioxide partial pressure in very low birth weight infants, and thus can be used to replace the electrode temperature of 42°C. Transcutaneous measurements at the lower electrode temperatures may be helpful for understanding the changing trend of blood oxygen partial pressure.
Blood Gas Monitoring, Transcutaneous ; Carbon Dioxide ; Electrodes ; Humans ; Infant ; Infant, Newborn ; Infant, Very Low Birth Weight ; Oxygen ; Partial Pressure ; Temperature

Biopsy ; Deep Learning ; Humans ; Male ; Neoplasm Grading ; Prostatectomy ; Prostatic Neoplasms

To develop a fluorescence polarization (FP)-based high-throughput screening (HTS) assay to identify novel small-molecule antagonists targeting β-catenin/TCF4 (T-cell factor 4) interaction, recombinant human β-catenin was expressed in Escherichia coli Rosetta (DE3) cells and purified by HisTrap^TM column. The bioactivity of purified β-catenin was further analyzed by enzyme-linked immunosorbent assay (ELISA). According to FP principle, the β-catenin/TCF4 binding model was performed, and fluorescence isothiocyanate (FITC) labeled TCF4 peptide (FITC-TCF4) served as the molecular probe of adaptor for binding to β-catenin. The FITC-TCF4 and β-catenin working concentration were optimized, and the binding conditions (complex stability and dimethylsulfoxide (DMSO) tolerance) have been investigated yet for further hits screening. The results showed that recombinant human β-catenin was successfully expressed and purified β-catenin exhibited favorable bioactivity in ELISA binding assay. Subsequently, the FP-based HTS assay was performed using 20 nmol·L^-1 FITC-TCF4 and 100 nmol·L^-1 β-catenin. Under these optimized conditions, a high Z´factor of 0.88 was achieved in a 384-well format and this FP-based HTS assay was very stable with regard to DMSO. Through screening of a natural-based product library (NBPL) using the established FP-based HTS assay, three hits (sanguinarine, chelerythrine, and compound S720) were identified as potential β-catenin/TCF4 interaction antagonists. Taken together, we have successfully developed a simple, robust and reliable FP-based HTS assay for screening of novel antagonists targeting β-catenin/TCF4 interaction.

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate