OBJECTIVE To explore the independent risk factors of voriconazole （VCZ）-related liver injury in elderly patients with hypoproteinemia. METHODS Elderly patients with invasive fungal infection and hypoproteinemia who were hospitalized in the respiratory intensive care unit of our hospital and treated with VCZ from August 2020 to July 2023 were selected. They were divided into group A （liver injury group） and group B （non-liver injury group） based on whether the liver injury occurred after using VCZ. Pearson correlation analysis was used to analyze the correlation between minimum concentration （cmin） of VCZ and inflammatory factor[C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）]， as well as liver function [alanine transaminase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBIL）]； univariate analysis was performed by using χ 2 test； Logistic regression analysis was used to analyze the independent risk factors affecting the occurrence of liver injury. RESULTS A total of 320 patients were included in the study， of whom 56 developed liver injury， with an incidence of 17.50%. The VCZ cmin in group A was significantly higher than group B （P＝ 0.021）. CRP， PCT， IL-6， and TBIL were correlated with VCZ cmin （P＜0.05）. CRP， PCT， IL-6， and TBIL had a significant impact on VCZ cmin （P＜0.05）. VCZ cmin， PCT， and TBIL were independent risk factors for liver injury （P＜0.05）. The patients with VCZ cmin≥3.76 mg/L had a significantly increased risk of liver injury. CONCLUSIONS VCZ cmin， PCT， and TBIL are independent risk factors for the occurrence of liver injury in elderly patients with hypoproteinemia. For patients with high PCT and TBIL， VCZ cmin and liver function should be closely monitored during VCZ treatment to reduce the risk of liver injury.

Objective:To investigate the predictive ability of Glypican-3 (GPC3) positive hepatocellular carcinoma based on the hepatobiliary specific contrast agent gadoxetate disodium enhancement of the liver imaging reporting and data system version 2018 (LI-RADS v2018) imaging features, and to assess the relevant clinical imaging features for postoperative recurrence in GPC3 positive HCC patients.Methods:This study was a cohort study. A total of 122 hepatocellular carcinoma patients who underwent gadoxetate disodium enhanced MRI examination with hepatic tumor resection in Henan Provincial People′s Hospital from January 2017 to December 2021 were retrospectively collected, including 96 GPC3 positive and 26 GPC3 negative patients. The imaging features defined by LI-RADS v2018 of HCC lesions were analyzed. Patients were followed up for 40 months to determine recurrence free survival (RFS). The logistic regression was used to analyze the risk factors of GPC3 positivity. An imaging model, and a clinical-imaging model which combined the patient′s alpha-fetoprotein levels were constructed. The efficacy of the model for predicting GPC3 positivity was assessed using receiver operating characteristic curves. Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the RFS between GPC3 positive and negative patients. Risk factors affecting the recurrence of GPC3 positive HCC were assessed by Cox regression.Results:The results of logistic multivariate regression analysis confirmed that rim enhancement ( OR=5.685, 95% CI 1.229-26.287, P=0.026) and irregular tumor margin at hepatobiliary phase ( OR=4.431, 95% CI 1.684-11.663, P=0.003) were independent risk factors for GPC3 positive HCC. The area under the curve for predicting GPC3 positivity was 0.745 (95% CI 0.636-0.854) for the imaging model and 0.776 (95% CI 0.677-0.876) for the clinical-imaging model. The mean RFS in the GPC3 positive group was 22 months, and it was 32 months in the negative group. There was a statistically significant difference in RFS between the two groups ( χ2=5.15, P=0.023). The multivariate Cox regression analysis showed that the arterial rim enhancement ( HR=5.460, 95% CI 1.966-15.162, P=0.001), microvascular invasion ( HR=2.402, 95% CI 1.210-4.769, P=0.012), portal vein tumor thrombus ( HR=3.226, 95% CI 1.114-9.344, P=0.031) were independent risk factors for recurrence after hepatic tumor resection for GPC3-positive HCC. Conclusions:A model based on the LI-RADS v2018 imaging features of hepatobiliary specific contrast agent gadoxetate disodium enhancement can effectively predict GPC3 positive HCC. The arterial rim enhancement, microvascular invasion and portal vein tumor thrombus are independent risk factors for postoperative recurrence of GPC3 positive HCC.

To analyze the factors associated with infection and death of carbapenem-resistant Klebsiella pneumoniae (CRKP) in patients. Using a case-control study method, patients with CRKP infection from January 2019 to December 2021 in the 3201 Hospital were selected as the case group, and patients with carbapenem-susceptible Klebsiella pneumoniae (CSKP) infection in the same period were selected as the control group in a ratio of 1∶1. The study subjects were followed up for 30 days. The two groups of patients were categorized into survival and death groups based on whether they died or not, respectively, and the 30-day morbidity and mortality rates of the CRKP case group and the CSKP control group were compared. The logistic regression model was used to analyze the factors associated with CRKP infection and death after CRKP infection. This study included 59 cases in the CRKP case group and 59 in the CSKP control group. The 30-day mortality rate of CRKP-infected patients and CSKP-infected patients were 30.5% (18/59) and 5.1% (3/59), with statistically significant differences ( P<0.001). Surgery within three months prior to KP infection ( OR=17.285, P=0.001), use of carbapenems within three months prior to KP infection ( OR=11.235, P=0.002), use of more than three types of antibiotics ( OR=7.993, P=0.016), albumin<30 g/L in patients prior to KP infection ( OR=10.463, P=0.002), sex ( OR=0.078, P<0.001), and diabetes ( OR=0.076, P=0.011) were associated factors of CRKP infection. Higher age-corrected Charlson Comorbidity Index scores of patients ( OR=1.522, P=0.024) and use of carbapenems by the patients with in the first three months prior to the KP infection ( OR=4.902, P=0.029) were associated factors for the deaths of patients with CRKP. In conclusion, medical personnel should be cautious in performing invasive procedures, strictly control the use of antibiotics, and provide targeted protection and treatment for high-risk patients as soon as possible.

Objective:To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection.Methods:A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data.Results:A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z ?=?-1.981, P ?=?0.048), aspartate aminotransferase (AST, z ?=?-3.956, P ?

To analyze the factors associated with infection and death of carbapenem-resistant Klebsiella pneumoniae (CRKP) in patients. Using a case-control study method, patients with CRKP infection from January 2019 to December 2021 in the 3201 Hospital were selected as the case group, and patients with carbapenem-susceptible Klebsiella pneumoniae (CSKP) infection in the same period were selected as the control group in a ratio of 1∶1. The study subjects were followed up for 30 days. The two groups of patients were categorized into survival and death groups based on whether they died or not, respectively, and the 30-day morbidity and mortality rates of the CRKP case group and the CSKP control group were compared. The logistic regression model was used to analyze the factors associated with CRKP infection and death after CRKP infection. This study included 59 cases in the CRKP case group and 59 in the CSKP control group. The 30-day mortality rate of CRKP-infected patients and CSKP-infected patients were 30.5% (18/59) and 5.1% (3/59), with statistically significant differences ( P<0.001). Surgery within three months prior to KP infection ( OR=17.285, P=0.001), use of carbapenems within three months prior to KP infection ( OR=11.235, P=0.002), use of more than three types of antibiotics ( OR=7.993, P=0.016), albumin<30 g/L in patients prior to KP infection ( OR=10.463, P=0.002), sex ( OR=0.078, P<0.001), and diabetes ( OR=0.076, P=0.011) were associated factors of CRKP infection. Higher age-corrected Charlson Comorbidity Index scores of patients ( OR=1.522, P=0.024) and use of carbapenems by the patients with in the first three months prior to the KP infection ( OR=4.902, P=0.029) were associated factors for the deaths of patients with CRKP. In conclusion, medical personnel should be cautious in performing invasive procedures, strictly control the use of antibiotics, and provide targeted protection and treatment for high-risk patients as soon as possible.

Objective:To analyze the clinical and pathological data of 15 patients with light chain amyloidosis initially diagnosed with other kidney diseases, and identify possible misdiagnosis reasons.Methods:It was a retrospective observational study. The clinical and pathological data of 15 patients, whose initial kidney biopsies failed to diagnose light chain-amyloidosis but were confirmed by a subsequent kidney biopsy or pathology consultation at Peking University First Hospital from January 2010 to December 2022 were collected. The results of immunofluorescence, Congo red staining, and electron microscopy of two renal biopsies were analyzed.Results:The median age of 15 patients was 56 years old, with a male-to-female ratio of 7∶8. The main clinical manifestation was massive proteinuria with normal kidney function, and there were 10 cases presenting as nephrotic syndrome. The initial diagnosis based on the first kidney biopsy included minimal change disease (8 cases), IgA nephropathy (3 cases), membranous nephropathy (3 cases), and type Ⅲ collagen glomerulonephritis (1 case). M proteinemia was not evaluated in 13 patients during the first kidney biopsy. Light chain immunofluorescence staining was not performed in 12 cases. Congo red staining was not performed in 13 cases. All fifteen patients received glucocorticoids combined with immunosuppressive therapy after their initial diagnosis, and 5 patients developed severe infection. After 12.0 (7.5, 20.0) months of treatment, none of them achieved clinical remission. Thirteen had evidences for M protein before the second kidney biopsy. The renal tissues of all patients underwent immunofluorescence light chain examination, Congo red staining, and immunoelectron microscopy examination when necessary. The repeat kidney biopsies of 14 cases and pathology consultation of one case consistently indicated light chain-amyloidosis. The kidney tissues in 13 cases were confirmed to be light chain restricted, 11 cases by immunofluorescence, and 2 cases by immune electron microscopy. After diagnosis of light chain-amyloidosis, all patients received targeted plasma cell therapy except for 1 patient lost to follow-up, 6 patients achieved hematologic remission, 5 patients achieved renal remission, 1 patient entered end-stage renal disease, and 3 patients died.Conclusions:In middle and elderly-aged patients with nephrotic syndrome, if conventional immunosuppressive therapy yields unsatisfactory results, it is crucial to focus on identifying evidences of monoclonal immunoglobulinemia, if necessary, kidney biopsy should be actively repeated. Kidney biopsy pathology should include comprehensive examinations such as light chain immunofluorescence, Congo red staining, and electron microscopy to avoid misdiagnosis of light chain-amyloidosis.

Objective:To investigate the effects of ovarian cancer domain containing protease-1 (OTUD1) gene on the typeⅠ interferon signaling pathway, and its impact on the antiviral effects of IFN-α.Methods:Dual-luciferase reporter assay was performed to detect the effects of OTUD1 gene on the transcriptional activity of interferon-stimulated response element (ISRE) promoter. Quantitative real-time PCR (qPCR) was used to detect the effects of OTUD1 on IFN-α-induced expression of interferon-stimulated genes (ISGs). The effects of OTUD1 gene on the expression of key proteins in the IFN-α signal transduction pathway were analyzed by Western blot, and its effects on IFN-α-mediated inhibition of hepatitis B virus replication were detected by qPCR and ELISA.Results:In HEK293T and Huh7.0 cells, OTUD1 down-regulated the transcriptional activity of ISRE promoter in the interferon signaling pathway and the expression of antiviral genes such as ISG15 and ISG56. In HEK293T cells, OTUD1 reduced the expression of phospho-Jak1 (p-JAK1) at protein level, but the catalytic inactive mutant of OTUD1 (C320S) could not regulate the expression of ISGs or p-JAK1. In Huh7.0 cells, OTUD1 antagonized the inhibitory effect of IFN-α on hepatitis B virus replication.Conclusions:OTUD1 with the ubiquitination activity can inhibit the interferon JAK-STAT signaling pathway and the expression of ISGs by down-regulating the expression of p-JAK1 protein. OTUD1 antagonizes the effect of IFN-α on viral replication and that may be related to the interferon-induced JAK-STAT signaling pathway.

Stroke often causes severe motor, sensory, and daily living function impairments, especially the recovery of distal limb extensor motor function is the most difficult. With the widespread application of Contralateral Control Functional Electrical Stimulation (CCFES) in stroke rehabilitation and continuous improvement of integrated wearable devices in recent years, it has been found that CCFES and combination therapy have good therapeutic effects in improving wrist extension and ankle dorsiflexion function in stroke patients. CCFES can improve both distal and proximal upper limb function, when applied to lower limbs, attention should be paid to the reverse coordination mechanism. Early intervention, sufficient treatment courses, and multiple combination CCFES treatment plans can accelerate the improvement of stroke patients' function.

Objective:To establish selection criteria of community mentors for postgraduates in general medicine.Methods:A subject index system of selection criteria of community tutors for general practice postgraduates was drafted and refined based on literature retrieving and in-depth interviews during January to December 2020. Twenty experts in general practice related fields were invited for two rounds of Delphi consultation. Analytic hierarchy process was used to calculate index weight coefficient and consistency test; and the developed selection criteria were evaluated.Results:Through the in-depth interviews with 11 general practice faculty and 11 general practice postgraduates, the following five first-level thematic frameworks were refined: (1) the professional qualities; (2) the basic qualities; (3) the clinical ability; (4) the teaching ability; (5) the scientific research ability. After two rounds of Delphi expert consultation, the selection criteria of community tutors for postgraduates in general practice were finally constructed, including 5 first-level indicators (professional quality, basic quality, medical practice ability, teaching and guidance ability, academic research ability) and 28 second-level indicators. The positive coefficients of experts were 85% and 100%; the expert authority coefficients were 0.825 and 0.860; and the expert opinion coordination coefficients were 0.486 and 0.515, respectively (all P<0.05). the weight coefficients of the five first-level indicators were 0.345, 0.210, 0.138, 0.210 and 0.097, respectively. Conclusion:The criteria and index system on the selection of community mentors for general practice postgraduates has been successfully developed in the study.

Objective:To investigate the value of mind map combined with blended teaching in improving the teaching quality of medicinal botany. Methods:A total of 102 students studying the course of medicinal botany were enrolled as subjects. The 51 students in the class of 2020 were enrolled as control group and received conventional teaching, and the 51 students in the class of 2021 were enrolled as observation group and received mind map combined with blended teaching. The two groups were assessed in terms of examination scores, critical thinking ability scores, self-learning ability scores, and student feedback on teaching quality. SPSS 22.0 was used for the t-test and the chi-square test. Results:Compared with the control group, the observation group had significantly higher examination scores ( t=3.01 and 3.14, P=0.003 and 0.002). After practice, both groups had increases in the scores of critical thinking ability and self-learning ability, and the observation group had significantly higher scores than the control group ( t=11.22 and 2.69, P<0.001 and P=0.008). Compared with the control group, the observation group had a better student feedback on teaching quality than the control group ( t=6.79, 7.83, 7.26, 7.43, and 8.54, P=0.009, 0.005, 0.007, 0.006, and 0.003). Conclusion:The combination of mind map and blended teaching can improve the examination scores of students and their critical thinking ability and self-learning ability, and students believe that this teaching model can help to improve teaching quality.