OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective To explore the value of constructing a model to predict the number of positive cores in systematic biopsy in prostate cancer(PCa)using a combination of radiomics features based on magnetic resonance imaging and clinical indicators.Methods Retrospectively collected magnetic resonance imaging and clinical data from two medical institutions(Gansu Provincial Hospital from January 2018 to February 2023,Zhangye People's Hospital Affiliated to Hexi College from April 2020 to February 2023).The 155 patients from Gansu Provincial Hospital were randomly divided into a training set(n=109;80 cases with positive needle count≥6 and 29 cases with positive needle count<6)and an internal validation set(n=46;34 cases with positive needle count≥6 and 12 cases with positive needle count<6)in a 7:3 ratio.The 43 patients from Zhangye People's Hospital Affiliated to Hexi College were used as external validation set.Small field of view high-resolution T2-weighted imaging(sFOV HR-T2WI)and contrast-enhanced delayed-phase images were selected to extract radiomic features from the three-dimensional region of interest of the entire prostate,and radiomics model was constructed and Radscores calculated after dimensionality reduction and feature selection.Univariate and multivariate logistic regressions were used to screen for independent risk factors for positive cores in systematic biopsy.Nomogram was constructed using Radscore and clinical independent risk factors to predict the number of positive cores in systematic biopsy in PCa patients,which was then externally validated.Results Age,alkaline phosphatase(ALP),free prostate specific antigen(FPSA),total prostate specific antigen(TPSA),FPSA/TPSA ratio,and prostate specific antigen density(PSAD)were not statistically significantly different between the training,internal validation,and external validation sets(P>0.05).FPSA,TPSA,FPSA/TPSA ratio,and PSAD were significantly different between the positive cores<6 and positive cores≥6 groups(P<0.001).Univariate logistic regression analysis showed that FPSA(P<0.001),TPSA(P<0.001),FPSA/TPSA ratio(P=0.001),PSAD(P<0.001),and Radscore(P<0.001)were risk factors for positive cores in systematic biopsy in PCa.Multivariate logistic regression analysis showed that PSAD(OR=0.251,95%CI 0.063-0.996,P=0.049)and Radscore(OR=1.990,95%CI 1.409-2.812,P<0.001)were independent risk factors for positive cores in systematic biopsy in PCa.The clinical models achieved AUCs of 0.849(95%CI 0.774-0.924),0.817(95%CI 0.693-0.941),and 0.631(95%CI 0.439-0.822);the 12 features for radiomics models are derived solely from sFOV HR-T2WI,the radiomics models achieved AUCs of 0.868(95%CI 0.791-0.945),0.846(95%CI 0.695-0.996),and 0.815(95%CI 0.660-0.970);the nomogram achieved AUCs of 0.921(95%CI 0.869-0.973),0.868(95%CI 0.743-0.992),and 0.840(95%CI 0.702-0.978)in the training set,internal validation set,and external validation set,respectively.Conclusions The combination of radiomic features extracted from sFOV HR-T2WI and PSAD can preoperatively be used as a noninvasive manner to predict the number of positive cores of the PCa patients.This approach has a certain value in risk stratification of PCa patients and guiding personalized clinical management.

Abstract:Objective　To investigate the clinical characteristics and early diagnostic methods of patients with Talaromyces marneffei infection, so as to reduce the mortality of patients. Methods The clinical characteristics and microbiological analysis data including fungal culture, smear examination and mass spectrometry were collected from 18 patients with Talaromyces marneffei infection in the Department of Respiratory Medicine, Department of Tuberculosis, and Department of Critical Respiratory Medicine in Fuzhou Pulmonary Hospital from January 2017 to December 2021, and descriptive analysis was conducted. Results　All the 18 patients were confirmed to be infected with Talaromyces marneffei by conventional culture and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS). The main infection sites of 18 patients with Talaromyces marneffei infection were lungs and lymph nodes, and the patients were accompanied by clinical manifestations such as cough, sputum and fever. The imaging features such as patchy shadows, mediastinal lymph node shadows and nodular shadows were common. Microbiological testing showed a statistically significant difference between smear and culture with a higher positive culture rate (χ2=13.74, P<0.05). The positive rate of blood culture in microbiological test was 60.0% (9/15), the positive rate of bronchial lavage fluid culture was 26.7% (4/15), the positive rate of sputum culture was 5.6% (1/18), one case each of pus, bone marrow, pleural fluid and cerebrospinal fluid was positive for culture and the other cases were negative, one case of sputum and one case of pus were positive for smear and the rest were negative. Colony characteristics showed that the colony morphology was mycelial phase at 25 ℃, producing red pigment, and the branching pattern of the penicillus was seen microscopically as monoverticillate or biverticillate; At 35 ℃, the yeast phase appeared at the initial stage, and then the mycelium phase changed after 5-6 days; the yeast phase was observed at 37 ℃, and yeast-like cells were seen under the microscope. All 18 patients with Talaromyces marneffei infection got better after using antifungal drugs. Compared with non-HIV patients with Talaromyces marneffei infection, leukopenia and anemia were common in HIV patients with Talaromyces marneffei infection, and the differences were statistically significant (P<0.05). 　Conclusions The infection of Talaromyces marneffei can be divided into localized type and disseminated type, which usually invade the lungs, skin, lymph nodes and other places. The main manifestations of patients are fever, cough, phlegm and other atypical symptoms. At present, the diagnosis of Talaromyces marneffei infection is mostly based on the fungal culture test, and the application of MALDI-TOF MS method can effectively shorten the diagnosis time of Talaromycosis marneffei. Clinical characteristics combined with microbiological analysis provide an objective basis for early diagnosis of patients with Talaromyces marneffei infection, and timely use of antifungal therapy can improve the prognosis of patients.

Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.
Animals ; Apoptosis ; Boron/toxicity* ; Mice ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Trichloroacetic Acid/toxicity* ; Tumor Suppressor Protein p53/metabolism*

BACKGROUND: The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults. METHODS: A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations. RESULTS: Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86-1.03) (P > 0.05), 0.77 (0.66-0.89) (P < 0.05), and 0.59 (0.40-0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85-0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82-0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake. CONCLUSIONS Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.