Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.

PI3K/AKT/mTOR signaling pathway plays a crucial role in cell proliferation, survival, differentiation, motility and intracellular transport. PI3Kδ, an isoform of PI3K, is highly expressed in B lymphocytes and is involved in the malignant progression of B-cell lymphoma. Thus, PI3Kδ has emerged as an attractive target for the development of anti-B-cell lymphoma drugs. Currently, there are several PI3Kδ inhibitors approved by the FDA for the treatment of B-cell lymphoma, each with its own characteristics, but also with varying degrees of adverse effects in clinical practice. Due to the complexity and diversity of the pathogenesis of B-cell lymphoma, single-target PI3Kδ inhibitors often have limited efficacy and are prone to drug resistance, and need to be combined with chemotherapy or other targeted drugs to enhance their efficacy. The future trend is to design novel inhibitors with higher efficacy and lower toxicity or to develop novel combination regimens with other chemotherapy, radiotherapy, and target drugs to acquire better anti-tumor effects with reduced adverse effects. This review summarizes the PI3Kδ inhibitors that have been approved for the treatment of B-cell lymphoma or are still in clinical trials, mainly focusing on their characteristics, adverse effects and combination regimens.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Objective:To evaluate the relationship between hemoglobin(Hb) level and the risk of diabetic retinopathy(DR) in patients with type 2 diabetes mellitus(T2DM).Methods:This study was a prospective cohort study. A total of 1 730 T2DM patients without DR, who received regular management at the Li′s Clinic in Taiwan, China starting from 2002, were selected as the study population. All patients underwent annual dilated fundus examination by professional ophthalmologists. General patient information and laboratory results were collected and analyzed. Based on the occurrence of DR during patient follow-up, patients were divided into the DR group and the non-DR(NDR) group. The impact of Hb levels on DR was explored using a generalized linear mixed model, and the relationship between Hb levels and DR was studied using Cox proportional hazards regression model.Results:After an average follow-up of 9.79 years, 481 patients with DR were detected. Compared with NDR group, DR group displayed a longer course of diabetes, higher rates of cataract, insulin use, and anemia, and higher systolic blood pressure, HbA 1C, and UACR as well as lower Hb. The results of the generalized linear mixed model showed a negative correlation between Hb and the occurrence of DR( β=-0.015, P<0.001). The Cox proportional hazards regression model showed that, after adjusting for confounding variables and based on quartiles of average Hb levels during follow-up, the risk of developing DR increased by 56.9% in the Q1 group(Hb≤127 g/L) compared to the Q4 group(Hb≥142 g/L). The cumulative risk plot showed that, after adjusting for confounding variables, the Q1 group had the highest cumulative risk of developing DR, and the difference was statistically significant( P<0.05). Conclusion:Hb was negatively correlated with DR, and the lower Hb levels were associated with the occurrence of DR, independent of other influencing factors.

To report the first case of chronic disseminated paracoccidioidomycosis in China. A 49-year-old male patient presented with papules and nodules of the skin for 1 year, and papules and ulcers on the oral mucosa for 2 months. Skin examination showed the edema of the left foot, multiple crusting ulcers on the sole of the left foot, ulcers with a granular base in the interdigital regions between the third and fourth toes as well as fourth and fifth toes of the left foot, accompanied by punctate hemorrhage and exudation; there were multiple papules, nodules, and plaques on the dorsum and medial side of the left foot and the left knee, with ulcers and crusts in the center; 2 papules were observed on the left wrist, and 1 papule on the left upper lip with a crusted surface; red plaques with ulcers and punctate hemorrhage were observed on the gingival mucosa, buccal mucosa, labial mucosa, and palate, and the lesions mainly occurred on the left side. Ultrasonography of superficial lymph nodes showed bilateral cervical and supraclavicular lymph node enlargement, which was more obvious on the left side. Computed tomography of the chest and abdomen showed diffuse miliary nodular shadows, and cordlike, cloudy flocculent and nodular high-density shadows in both lungs, as well as obvious thickening of the left adrenal gland in the abdomen. Yeast cells were observed by immunofluorescent staining of biopsy tissues from the oral mucosa and left lower limb. Histopathological examination of biopsy tissues from the oral mucosa and left lower limb showed granulomatous inflammation, and refractive double-membrane yeast cells could be observed inside or outside the multinucleated giant cells, without or with a single bud or multiple buds; periodic acid-Schiff staining and hexamine silver staining of the above biopsy tissues were positive. Fungal culture of the left lower limb lesion in Sabouraud dextrose agar medium at 25℃ and 37℃ both yielded fungal hyphae. Metagenomics sequencing of the oral mucosal tissue and alveolar lavage fluid indicated the infection with Paracoccidioides brasiliensis. The diagnosis of chronic disseminated paracoccidioidomycosis was confirmed. After 1-month oral treatment with itraconazole capsules at a dose of 400 mg/d, the lesions on the skin and oral mucosa markedly improved, and computed tomography imaging of the lung and left adrenal gland also showed obvious improvement. The dose of itraconazole was reduced to 200 mg/d after 3 months. The patient′s condition further improved during a 10-month follow-up.

Objective:To explore the correlation between nurses ' empowerment and professional identity in Cardiac Intensive Care Unit (CCU) . Methods:From June to September 2021, 164 nurses working in CCU of 8 ClassⅢ Grade A hospitals in Zhengzhou were selected as the research object by convenience sampling. The General Information Questionnaire, Professional Identity Scale for Nurses and Empowering Leadership Behavior Scale were used to conduct the questionnaire survey. A total of 164 questionnaires were distributed, and 158 valid questionnaires were recovered, with a valid recovery rate of 96.34% (158/164) .Results:Among 158 CCU nurses, the total scores of the Professional Identity Scale for Nurses and the Empowering Leadership Behavior Scale were (93.24±6.05) and (84.30±7.15) respectively. There was a positive correlation between the total score of Professional Identity Scale for Nurses and the total score of Empowering Leadership Behavior Scale ( P<0.05) . Conclusions:CCU nurses ' professional identity is at the middle level, while empowerment is closely related to their professional identity. Nursing managers should pay attention to the implementation of effective empowerment behavior, improve the professional identity of CCU nurses, and promote the stability of the nursing team.

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

Hand, foot and mouth disease (HFMD) is an acute infectious disease induced by enterovirus. More than 30 pathogenic viruses for hand, foot and mouth disease have been discovered, of which enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16) are the most common. Enterovirus 71 (EV-A71) is also the main cause of severe hand, foot and mouth disease. In recent years, it has been discovered that Coxsackievirus A6 (CV-A6) infection has broken out in many regions of the world, and the pathogenicity rate is increasing, which indicatesthat it may rise to become a new major pathogenic agent of hand, foot and mouth disease. Hand, foot and mouth disease has become a global public health problem. Therefore, research on the pathogenic mechanism of multiple enteroviruses that induce hand, foot and mouth disease and analysis of its epidemiology will become the top priority of prevention, control and treatment of the disease.

Objectives:To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer.Methods:The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ 2 test. Results:Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months, P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%, P<0.05;32.9% vs. 21.9%, P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%, P>0.05). Conclusions:The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients′ compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.