Objective To investigate the predictive value of the combined tumor burden score (TBS) and platelet-albumin-bilirubin (PALBI) score model for postoperative tumor recurrence in liver transplant recipients with hepatocellular carcinoma (HCC). Methods The general information of 158 recipients diagnosed with HCC and underwent liver transplantation at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from 2008 to 2021 was collected. Lasso regression analysis combined with multivariate Cox regression analysis were used to identify independent risk factors for postoperative tumor recurrence after liver transplantation with HCC. A nomogram prediction model was constructed based on variables selected by Lasso regression analysis, and the predictive performance of the model was verified by calibration curve and clinical decision curve. The optimal cut-off values for postoperative tumor recurrence in liver transplant recipients with HCC were determined by receiver operating characteristic (ROC) curve, and Kaplan-Meier analysis was used to compare survival differences among different groups. Results Among the 158 liver transplant recipients with HCC, 82 experienced tumor recurrence, with a recurrence rate of 51.9% and a median tumor-free survival time of 10 (4, 25) months. Results of Lasso regression analysis and multivariate Cox regression analysis showed that alpha-fetoprotein (AFP) ≥400 ng/mL, TBS and PALBI score were all independent risk factors for postoperative tumor recurrence in liver transplant recipients with HCC (all P<0.05). The combined high TBS-high PALBI score showed the highest predictive value (hazard ratio 6.909, 95% confidence interval 3.067-15.563, P<0.001). A nomogram prediction model was constructed based on six variables selected by Lasso regression analysis. Calibration curve showed good consistency between the model's predicted results and the ideal curve. Decision curve analysis indicated that the nomogram prediction model provided the highest clinical benefit for predicting 1-year tumor-free survival after liver transplantation with HCC. Time-dependent ROC curves at 1, 3 and 5 years after surgery showed that TBS-PALBI model had good predictive performance, with no significant difference in area under the curve (AUC) compared with TBS-PALBI-AFP model. The optimal cut-off values for predicting postoperative tumor recurrence were determined by ROC curve, with a PALBI score cut-off of −2.334 and a TBS cut-off of 5.305. Recipients were divided into a low TBS-low PALBI score group (n=47) and a low/high TBS-low/high PALBI score group (at least one score was high) (n=111). Kaplan-Meier survival analysis showed that the low TBS-low PALBI score group had a higher tumor-free survival rate than the low/high TBS-low/high PALBI score group, with a significant difference (P<0.05). Conclusions TBS-PALBI model provides a novel, simple and effective tool for assessing the prognosis of liver transplant recipients with HCC. The nomogram model constructed based on this has significant advantages in predictive performance and may serve as a reference for guiding individualized treatment plans and improving clinical outcomes.

Objective:To analyze the efficacy and safety of integrase inhibitor-based single-tablet regimens bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and lamivudine/dolutegravir (3TC/DTG) in the treatment-na?ve patients with acquired immunodeficiency syndrome (AIDS).Methods:This study was a retrospective cohort study. The clinical data of treatment-na?ve AIDS patients initiating anti-retroviral therapy (ART) with B/F/TAF or 3TC/DTG and on ART for greater than or equal to 24 weeks from October 2020 to July 2023 in Shanghai Public Health Clinical Center, Fudan University were collected. The baseline human immunodeficiency virus (HIV)-1 RNA, CD4 + T lymphocyte counts at baseline and 12 weeks of treatment, and the rates of virological suppression and virological failure at 24 weeks of treatment, and levels of total cholesterol, serum creatinine, uric acid before and after treatment were compared between the B/F/TAF group and 3TC/DTG group. Independent sample t test, corrected t test, Mann-Whitney U test, Wilcoxon signed rank test, chi-square test were used for statistical analysis. Results:Among 189 treatment-na?ve AIDS patients, 141 cases were in B/F/TAF group and 48 cases in 3TC/DTG group. The HIV-1 RNA level at baseline was 1.77(0.78, 4.52)×10 5 copies/mL in the B/F/TAF group and 0.97(0.24, 2.20)×10 5 copies/mL in the 3TC/DTG group. There was a statistically significant difference between the two groups ( U=2 221.00, P=0.006).There were 77.3%(109/141) patients on B/F/TAF achieved complete virological suppression with no virological failure at week 24, and 85.4%(41/48) on 3TC/DTG achieved complete virological suppression with one (2.1%) virological failure at week 24. At 12 weeks of treatment, 92.2%(130/141) of the patients in the B/F/TAF group and 85.4%(41/48) of the patients in the 3TC/DTG group had an increase in CD4 + T lymphocyte count by more than 30% compared with baseline. The proportion of CD4 + T lymphocyte count increased by more than 100/μL from baseline in the B/F/TAF group was 67.4%(95/141), and that in the 3TC/DTG group was 52.1%(25/48). There were no significant differences between the two groups ( χ2=1.91 and 3.61, respectively, P=0.167 and 0.733).The levels of total cholesterol ( W=2 036.00, t=-5.42, respectively), serum creatinine ( W=1 098.00, 234.00, respectively), uric acid ( W=2 188.00, 299.00, respectively) and the proportion of patients with mild to moderate renal insufficiency ( χ2=22.29, 8.22, respectively) in the B/F/TAF group and 3TC/DTG group after 24 weeks of treatment were significantly higher than those before treatment (all P<0.01). Conclusions:Both B/F/TAF and 3TC/DTG are effective in terms of virological suppression and immunological recovery and have good safety profiles in treatment-na?ve patients with AIDS.

Objective:To analyze the changes of pathogen spectrum of pulmonary infection in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients before and during coronavirus disease 2019 (COVID-19) epidemic.Methods:The clinical data of hospitalized HIV infection/AIDS patients with pulmonary infection confirmed by etiology and/or imaging examinations in the Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University from January 2017 to December 2022 were collected, including the types of pathogens, the peripheral blood CD4 + T lymphocyte counts at admission due to pulmonary infection, and the treatment outcome of the patients at discharge. The changes of pathogen spectrum of pulmonary infection before COVID-19 epidemic (2017 to 2019) and during the epidemic (2020 to 2022) were analyzed, and their effects on adverse treatment outcomes (death during hospitalization or automatic discharge) were analyzed. Statistical analysis was performed using the chi-square test, trend chi-square test or Kruskal-Wallis test. Results:The proportion of patients with pulmonary infection during the epidemic was lower than that before the epidemic, the difference was statistically significant (23.01%(1 061/4 612) vs 28.68%(1 463/5 102), χ2=40.76, P<0.001). From 2017 to 2022, the proportion of hospitalized HIV infection/AIDS patients with pulmonary infection showed a downward trend ( χ2trend=8.81, P<0.001). Among the pathogens causing pulmonary infection from 2017 to 2022, bacteria, mycobacteria, and fungi were the three main pathogenic pathogens, accounting for 48.77%(1 231/2 524), 32.13%(811/2 524), and 14.34%(362/2 524), respectively. The proportion of bacterial infection decreased from 55.02%(805/1 463) before the epidemic to 40.15%(426/1 061) during the epidemic, and the proportion of fungal infection increased from 9.23%(135/1 463) to 21.39%(227/1 061), the differences were both statistically significant ( χ2=54.45 and 74.11, respectively, both P<0.001). There was no significant difference in the proportion of mycobacteria between before and during the epidemic ( P=0.169), but the proportion of Mycobacterium tuberculosis (MTB) infection decreased from 22.01%(322/1 463) before the epidemic to 15.08%(160/1 061) during the epidemic, while the proportion of nontuberculous mycobacterium (NTM) infection increased from 7.11%(104/463) to 11.78%(125/1 061), the differences were both statistically significant ( χ2=19.11 and 16.28, respectively, both P<0.001). There was a significant difference in the pathogen spectrum of pulmonary infection before and during the epidemic ( χ2=128.91, P<0.001). There was a significant difference in the peripheral blood CD4 + T lymphocyte counts of patients with MTB, NTM, Pnenmocystis, Talaromycosis marneffei and Cryptococcus infection ( H=71.92, P<0.001). There were 63.74%(109/171) of Pneumocystis infection and 67.65%(69/102) of Talaromycosis marneffei infection occurred in patients with CD4 + T lymphocyte count<50/μL. Among the patients with pulmonary infection, the proportion of patients with adverse treatment outcomes during the epidemic was higher than that before the epidemic, and the difference was statistically significant (13.29%(141/1 061) vs 10.39%(152/1 463), χ2=5.04, P=0.025). Among the patients with pulmonary infection who developed adverse treatment outcomes, the top three pathogens (from high to low) were bacteria (63.48%(186/293)), mycobacteria (27.65%(81/293)), and fungi (6.83%(20/293)). The proportion of adverse treatment outcomes caused by bacterial infection decreased during the epidemic compared with that of before the epidemic (71.71%(109/152) vs 54.61%(77/141), χ2=9.23, P=0.002), while the proportion of adverse treatment outcomes caused by fungal infection increased (2.63%(4/152) vs 11.35%(16/141), χ2=8.74, P=0.003), and the differences were both statistically significant. The proportion of adverse treatment outcomes caused by mycobacterial infection increased, but without statistically significant (23.03%(35/152) vs 32.62%(46/141), χ2=3.37, P=0.066), among which there was no difference in the proportion of adverse treatment outcomes caused by MTB infection (13.82%(21/152) vs 14.89%(21/141), χ2=0.07, P=0.793), while the proportion of adverse treatment outcomes caused by NTM infection increased (5.92%(9/152) vs 14.89%(21/141), χ2=6.41, P=0.011). There was a significant difference in the pathogen spectrum of pulmonary infection patients with adverse treatment outcomes before and during the epidemic ( χ2=12.22, P=0.007). Conclusions:Among the spectrum of pathogens causing pulmonary infection and adverse treatment outcomes of HIV infection/AIDS patients during the epidemic, compared with that before the epidemic, the proportion of bacterial decreases, while the proportion of fungi increases, and the proportion of mycobacteria remains stable with the proportion of NTM increasing. The proportion of MTB causing pulmonary infection decreases, while the proportion of MTB causing adverse treatment outcomes remains stable.

Humans ; COVID-19 ; HIV Infections/drug therapy* ; Risk Factors

Humans ; HIV-1 ; Leukocytes, Mononuclear ; Lymphoma, Non-Hodgkin ; DNA ; HIV Infections

Objective:To analyze the clinical and epidemiological characteristics and changing trends of acquired immunodeficiency syndrome (AIDS)-associated talaromycosis in Shanghai City.Methods:The clinical data of patients with AIDS-associated talaromycosis hospitalized at Shanghai Public Health Clinical Center, Fudan University from Janauary 1, 2014 to December 31, 2021 were collected. The medical information included age, gender, place of origin, clinical symptoms, imaging manifestations, blood routine test, CD4 + T lymphocyte count. The chi-square test or Fisher exact probability test was used for statistical analysis. Univariate logistic regression was used to analyze the related risk factors for death. Results:From 2014 to 2021, a total of 12 165 AIDS patients were admitted, including 169 (1.4%) AIDS-assiociated talaromycosis patients. The proportions of AIDS-associated talaromycosis in AIDS inpatients from 2014 to 2021 were 1.8%(21/1 149), 1.1%(14/1 307), 1.3%(19/1 446), 0.9%(15/1 610), 1.2%(20/1 626), 1.2%(22/1 778), 1.7%(28/1 624) and 1.8%(30/1 625), respectively, which had not changed much. There was no statistically significant difference in the proportion of AIDS-associated talaromycosis in AIDS inpatients in different years ( χ2=9.50, P=0.218). Among the 169 patients, 157 cases (92.9%) were male, with the age of (37.9±12.2) years, and 35 were from Jiangxi Province, 31 from Shanghai Municipality, 29 from Zhejiang Province, 17 from Anhui Province, 14 from Fujian Province, 11 from Jiangsu Province, eight from Hunan Province, four from Heilongjiang Province, three cases each from Guangxi Zhuang Autonomous Region, Guizhou Province and Henan Province, two cases each from Hubei Province, Shandong Province, Shanxi Province, Yunnan Province and Guangdong Province, and one case from Chongqing Municipality. Patients from non-traditional endemic areas did not find a clear history of living in traditional endemic areas. Of 169 patients, 143(84.6%) cases had fever, 73(43.2%) had respiratory symptoms, and 26(15.4%) had rash during the course of the disease, 147(87.0%) had pulmonary imaging abnormalities, 94(55.6%) were complicated by other pathogens, and 44(26.0%) had hepatosplenomegaly, 137(81.1%) had CD4 + T lymphocyte count <50/μL. Twenty-three patients died, with the total fatality rate of 13.6%. The overall mortality rate showed a downward trend year by year. There was a statistically significant difference in the case fatality rate of AIDS-associated talaromycosis in different years (Fisher exact probability test, P=0.046). The result of univariate logistic regression model showed that patients with platelet count<50×10 9/L had an increased risk of death (odds ratio ( OR)=3.33, 95% confidence interval ( CI) 1.13 to 9.81, P=0.029). Conclusions:The overall change of AIDS-associated talaromycosis inpatients in Shanghai is not significant, while the prevalence rate has increased slightly in recent two years. The case fatality rate is declining year by year. The proportions of patients without a history of living in or traveling to epidemic areas and without rash as the first manifestation are high, and the main clinical manifestation is multi-system damage. Patients with platelet count<50×10 9/L have an increased risk of death.

Objective:To explore the clinical characteristics of acquired immunodeficiency syndrome (AIDS) complicated with nontuberculous mycobacteria (NTM) disease.Methods:The clinical data of 190 patients with AIDS complicated with NTM disease diagnosed by Shanghai Public Health Clinical Center, Fudan University from January 1, 2019 to December 31, 2021 were analyzed retrospectively. NTM diseases were divided into disseminated NTM disease group and non-disseminated NTM disease group. The independent sample t test, Mann Whitney U test and chi-square test were used for statistical analysis. Results:The 190 patients with AIDS complicated with NTM disease included 182 males and eight females. The age was (42±13) years old, and the first hospital stay was 15(6, 26) days. Pneumocystis carinii pneumonia was the most common co-infection in 12.1%(23/190) of patients, 87 cases (45.8%) were disseminated NTM disease. The clinical symptoms of patients were common in fever (55.8%(106/190)), cough (50.0%(95/190)), and expectoration (28.9%(55/190)). The proportions of fatigue (31.0%(27/87) vs 7.8%(8/103)), poor appetite (21.8%(19/87) vs 10.7%(11/103)) in the AIDS patients with disseminated NTM disease group were higher than those in the non-disseminated NTM disease group, and the differences were statistically significant ( χ2=16.99, P<0.001 and χ2=4.42, P=0.036, respectively). There was no significant difference in the proportions of deaths between AIDS patients with disseminated NTM disease and those without disseminated NTM disease (17.2%(15/87) vs 12.6%(13/103), χ2=0.80, P=0.371). The most common NTM species was Mycobacterium avium (67.1%(49/190)), followed by Mycobacterium kansasii (15.1%(11/190)). Hemoglobin ((90.3±23.9) g/L vs (110.1±24.2) g/L), albumin ((29.7±5.5) g/L vs (34.7±5.6) g/L), CD4 + T lymphocyte count (11(5, 30)/μL vs 52(16, 96)/μL) and CD8 + T lymphocyte count ((362±320)/μL vs (496±352)/μL) in the disseminated NTM disease group were lower than those in non-disseminated NTM disease group ( t=-5.63, P<0.001; t=-6.18, P<0.001; Z=-5.90, P<0.001; and t=-2.73, P=0.007, respectively), while procalcitonin (0.24(0.10, 0.77) μg/L vs 0.10 (0.04, 0.51) μg/L) was higher than that in the non-disseminated NTM disease group ( Z=-3.09, P=0.002), with statistical significance. The most common imaging features were lung patch and strip shadow (67.4%(128/190)). Conclusions:The most common type of AIDS patients complicated with NTM disease is disseminated NTM disease, and Mycobacterium avium is the most common NTM species. The clinical manifestations (fatigue, anorexia) and laboratory tests (hemoglobin, albumin, procalcitonin, CD4 + T lymphocyte count, CD8 + T lymphocyte count) of AIDS patients with disseminated NTM disease and non-disseminated NTM disease are different, while the prognosis is not significantly different.

Objective:To investigate the value of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI in predicting the pathological grade and early recurrence rate of hepatocellular carcinoma.Methods:The imaging data, pathological data, and follow-up data of 90 patients with hepatocellular carcinoma who underwent Gd-EOB-DTPA-enhanced MRI examination and surgical treatment in People's Hospital of Baise from January 2016 to October 2017 were retrospectively analyzed. The correlation between the signal intensity of contrast-enhanced MRI and postoperative pathological grade was analyzed. Kaplan-Meier survival analysis was performed to investigate the effects of the signal characteristics of hepatobiliary lesions on the early recurrence rate of hepatocellular carcinoma.Results:A total of 59 (65.56%) patients showed low-intensity signals and 31 (34.44%) patients showed mixed-intensity signals. High-intensity signal was not found in any patients. The signal intensity of the hepatobiliary phase was significantly correlated with the pathological grade of the tumor ( χ2 = 2.26, P = 0.040) and tumor size ( t = 3.10, P = 0.033). The early recurrence rate of hepatocellular carcinoma was significantly higher in patients exhibiting mixed-intensity signals than that in patients exhibiting low-intensity signals ( χ2 = 2.25, P = 0.041). Conclusion:Gd-EOB-DTPA-enhanced MRI in the hepatobiliary phase with different signal intensities has the potential to predict the pathological grade and early recurrence rate of hepatocellular carcinoma.

Background: The treatment of trigeminal neuralgia remains a challenging issue.Stem cells from human exfoliated deciduous teeth (SHED) provide optimized therapy for chronic pain. This study aimed to investigate the mechanisms underlying the attenuation of trigeminal neuralgia by SHED. Methods: Trigeminal neuralgia was induced by chronic constriction injury of the infraorbital nerve. The mechanical threshold was assessed after model establishment and local SHED transplantation. Endoplasmic reticulum (ER) morphology and Caspase12 expression in trigeminal ganglion (TG) was evaluated as well. BiP expression was observed in PC12 cells induced by tunicamycin. Results: The local transplantation of SHED could relieve trigeminal neuralgia in rats.Further, transmission electron microscopy revealed swelling of the ER in rats with trigeminal neuralgia. Moreover, SHED inhibited the tunicamycin-induced up-regulated expression of BiP mRNA and protein in vitro. Additionally, SHED decreased the up-regulated expression of Caspase12 mRNA and protein in the TG of rats caused by trigeminal neuralgia after chronic constriction injury of the infraorbital nerve mode. Conclusions This findings demonstrated that SHED could alleviate pain by relieving ER stress which provide potential basic evidence for clinical pain treatment.

Objective:This study aims to reveal the special immune infiltrating environment and possible immune escape mechanism of giant cell tumor of bone through single-cell sequencing data.Methods:The fresh samples obtained from 4 patients with primary giant cell tumor of bone from January 2018 to December 2021 were collected, and single-cell transcriptome sequencing was performed on the 10X platform to explore the characteristics and immune environment of giant cell tumor of bone by using t-distributed stochastic neighbor embedding ( t-SNE). The main cell types and signal pathways of immune cell regulation and function in giant cell tumor of bone were observed by cell communication analysis. Results:Cell clustering, the definition of basic cell types, the classification of immune cells, and the mutual regulatory relationship between cell types were analyzed for 35 643 single-cell data from 4 giant cell tumor samples of bone. It was found that giant cell tumor of bone was composed of 9 basic cell types, in which the immune cells were mainly CD8 + T cells (51%) and the non-immune cells were mainly fibroblast like spindle stromal cells (74%). The immune infiltration of giant cell tumor of bone is dominated by cytotoxic CD8 + T cells and lacks exhausted CD8 + T cells. CD4 + T cells are characterized by high expression of immune checkpoint genes CTLA4 and TIGIT. In giant cell tumor of bone, immune cells mainly act on multinucleated osteoclast like giant cells through PARs and CCL signaling pathways, but not stromal cells. Conclusion:This study defined the main cell types of giant cell tumor of bone through single cell sequencing data, and further revealed the composition characteristics of its immune infiltration, and found that the target of its immune cells was mainly multinuclear osteoclast like giant cells, which provided effective information for further understanding the occurrence and development of giant cell tumor of bone.