Objective:To examine the manifestations and causes of administrative burden among primary healthcare professionals,and to explore its impact on job burnout through the mediating role of role conflict,providing theoretical and empirical support for governance-level burden-reduction strategies.Methods:An exploratory sequential mixed-methods design was employed,focusing on primary healthcare professionals in Shandong Province.In the first phase,in-depth interviews were conducted with 175 participants;in the second phase,a questionnaire survey of 1,096 participants and follow-up interviews with 107 participants were carried out.Results:The proportions of respondents who reported"heavy"or"very heavy"burdens were 62.7%for inspection,54.8%for documentation,51.8%for reporting,and 24.4%for meetings.Structural equation modeling showed that administrative burden had a direct effect on job burnout(0.150)and an indirect effect through role conflict(0.093).Qualitative findings further indicated that administrative burden largely stemmed from public health traceability requirements and medical insurance policies,and operated through both resource-based and value-based conflicts.Conclusions:Primary healthcare professionals face considerable administrative burdens,which may heighten job burnout through role conflict.Governance reforms should optimize inspection and assessment,streamline data reporting,refine record-keeping,and promote collaborative governance to break the chain of institutional pressure leading to burnout.

Aim To establish a simple and practical method for visualizing neurovascular coupling in the mouse barrel cortex in vivo.Methods Male C57BL/6J mice received stereotaxic in-jections of pAAV-hSyn-jGCaMP7s-WPRE into the barrel cortex to monitor neuronal activity.Three weeks post-injection,a crani-al window was implanted,and TRITC-Dextran 155 ku was ad-ministered intravenously to visualize the vasculature and blood flow dynamics.A custom-built whisker stimulator was used to e-voke controlled neuronal excitation.Two-photon microscopy was employed to monitor neuronal and vascular responses to whisker stimulation in real-time.Results Neuronal calcium signals and plasma signals were clearly observed using two-photon microsco-py.Whisker stimulation led to a significant increase in neuronal calcium signals in the barrel cortex,indicating effective neuronal activation.This neuronal excitation was accompanied by a syn-chronous increase in blood vessel diameter,blood flow velocity and overall blood flow.Conclusions This study successfully establishes a three-dimensional visualization framework(spatial,temporal,and functional)for in vivo visualization of neurovascu-lar coupling in the mouse barrel cortex,which provides a useful tool for investigating the pathophysiological mechanisms of neuro-vascular dysfunction and evaluating the efficacy of potential ther-apies.

Objective:To examine the manifestations and causes of administrative burden among primary healthcare professionals,and to explore its impact on job burnout through the mediating role of role conflict,providing theoretical and empirical support for governance-level burden-reduction strategies.Methods:An exploratory sequential mixed-methods design was employed,focusing on primary healthcare professionals in Shandong Province.In the first phase,in-depth interviews were conducted with 175 participants;in the second phase,a questionnaire survey of 1,096 participants and follow-up interviews with 107 participants were carried out.Results:The proportions of respondents who reported"heavy"or"very heavy"burdens were 62.7%for inspection,54.8%for documentation,51.8%for reporting,and 24.4%for meetings.Structural equation modeling showed that administrative burden had a direct effect on job burnout(0.150)and an indirect effect through role conflict(0.093).Qualitative findings further indicated that administrative burden largely stemmed from public health traceability requirements and medical insurance policies,and operated through both resource-based and value-based conflicts.Conclusions:Primary healthcare professionals face considerable administrative burdens,which may heighten job burnout through role conflict.Governance reforms should optimize inspection and assessment,streamline data reporting,refine record-keeping,and promote collaborative governance to break the chain of institutional pressure leading to burnout.

Aim To establish a simple and practical method for visualizing neurovascular coupling in the mouse barrel cortex in vivo.Methods Male C57BL/6J mice received stereotaxic in-jections of pAAV-hSyn-jGCaMP7s-WPRE into the barrel cortex to monitor neuronal activity.Three weeks post-injection,a crani-al window was implanted,and TRITC-Dextran 155 ku was ad-ministered intravenously to visualize the vasculature and blood flow dynamics.A custom-built whisker stimulator was used to e-voke controlled neuronal excitation.Two-photon microscopy was employed to monitor neuronal and vascular responses to whisker stimulation in real-time.Results Neuronal calcium signals and plasma signals were clearly observed using two-photon microsco-py.Whisker stimulation led to a significant increase in neuronal calcium signals in the barrel cortex,indicating effective neuronal activation.This neuronal excitation was accompanied by a syn-chronous increase in blood vessel diameter,blood flow velocity and overall blood flow.Conclusions This study successfully establishes a three-dimensional visualization framework(spatial,temporal,and functional)for in vivo visualization of neurovascu-lar coupling in the mouse barrel cortex,which provides a useful tool for investigating the pathophysiological mechanisms of neuro-vascular dysfunction and evaluating the efficacy of potential ther-apies.

Objective:To analyze the incidence of abnormal hemoglobin(Hb)in neonates in Guangzhou area,as well as the results of quantitative analysis of Hb in neonatal umbilical cord blood and genetic diagnosis of thalassemia in neonates with abnormal Hb;And to explore the hematological phenotypes and clinical characteristics of neonates with abnormal Hb and their parents,providing a reference for eugenics and childcare.Methods:650 neonates born at Guangdong Provincial People's Hospital who underwent Hb electrophoresis were included in this study.The results of routine blood test of umbilical cord blood,Hb electrophoresis and α-,β-thalassemia gene detection of the neonates were collected.The genotype distribution of thalassemia in the neonates was analyzed.Additionally,the abnormal Hb content of α and β variants was studied.Furthermore,the differences in hematological parameters between abnormal Hb neonates and normal neonates and α-thalassemia neonates,as well as between the parents of abnormal Hb neonates and normal adults were compared.Results:Among the 650 neonates,332(51.08％)were diagnosed with thalassemia,including 235 cases of α-thalassemia(36.15％),79 cases of β-thalassemia(12.15％),and 18 cases of compound α β-thalassemia(2.77％).Among all the α-thalassemia genotypes,the most prevalent one was--SEA/α α(48.94％),followed by-α3.7/α α(20.00％),-α42/α α(11.06％),and α α CS/α α(8.94％).The four most common genotypes of β-thalassemia were β CD41-42(32.91％),βIVS-Ⅱ-654(26.58％),β-28(21.52％),and β E(10.13％),respectively.275 cases of abnormal bands were found in Hb electrophoresis of umbilical cord blood,with a detection rate of 42.31％.The abnormal Hb content ofα-variant in the neonates was significantly higher than that of β-variant(P＜0.001).The levels of Hb,MCV,MCH,Hb A,and Hb F in neonates with abnormal Hb were lower than those in normal neonates,while the RDW-CV was higher than that in normal neonates,with statistical significantce(P＜0.05).The levels of RBC and Hb A in neonates with abnormal Hb were lower than those in neonates with α-thalassemia,while the level of MCH was higher than that in neonats withα-thalassemia,with statistical significance(P＜0.05).The levels of Hb,MCV,MCH,and Hb A in parents of neonates with abnormal Hb were lower than those in normal adults,while the RDW-CV was higher than that in normal adults,and the differences were statistically significant(P＜0.05).Conclusion:The abnormal Hb content of α-variant in the neonates is significantly higher than that of β-variant in the neonates in Guangzhou,which can help to presume whether it isα chain or β chain based on the abnormal Hb content,providing a reference for globin gene sequencing.Meanwhile,analysis of various hematological screening-related indicators in neonates in the early stage is beneficial for early warning of the occurrence of abnormal Hb combined with thalassemia,reducing missed diagnoses to a certain extent.

Objective:To investigate the incidence of PTPN11 gene mutation and its associated gene mutations in adult patients with acute myeloid leukemia(AML),and analyze its clinical characteristics.Methods:Second-generation sequencing and Sanger sequencing were used to detect 51 gene mutations,and multiplex-PCR was used to detect 41 fusion genes from 451 newly diagnosed adult AML patients admitted to Affiliated Hospital of Jiangnan University,Changzhou Second People's Hospital,Wuxi People's Hospital and Wuxi Second People's Hospital from January 2017 to July 2022.Results:Among 451 primary adult AML patients,the PTPN11 gene mutation was detected in 34 cases,and the mutation rate was 7.5％.In the 34 patients,37 PTPN11 alterations were found,which were exclusively missense mutations affecting residues located within the N-SH2(31 cases)and PTP(6 cases)domains and clustered overwhelmingly in exon 3.The platelet count of PTPN11 mutation patients was 76.5(23.5,119.0)× 109/L,which was significantly higher than 41.0(22.0,82.5)×109/L of wild-type patients(P＜0.05).While,there were no significant differences in sex,age,peripheral white blood cell count,hemoglobin,and bone marrow blast between PTPN11 mutation and wild-type patients(P＞0.05).In FAB subtypes,PTPN11 mutations were mainly distributed in M5,followed by M2 and M4,less frequently in M3 and M6.There was no significant difference in the distribution of FAB subtypes between PTPN11 mutation and wild-type patients(P＞0.05).A total of 118 AML patients were detected positive fusion gene,among which patients with PTPN11 mutations had a higher incidence of positive MLL-AF6 than wild-type ones(P＜0.01).97.1％of 34 patients with PTPN11 mutations were accompanied by other mutations,in descending order,they were respectively NPM1(38.2％),NRAS(32.4％),FLT3-ITD(32.4％),DNMT3A(32.4％)and KRAS(23.5％),etc.Conclusion:PTPN11 mutation has a certain incidence in AML patients and is clustered overwhelmingly in exon 3.ALL of them are exclusively missense mutations,and most often present in conjunction with NPM1 mutations.FAB typing of PTPN11 mutation is mostly manifested as M5 subtype,which is associated with higher platelet counts.

Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.
Mice ; Animals ; Humans ; Hepatitis, Autoimmune/pathology* ; Signal Transduction ; Disease Models, Animal ; Stem Cells

Objective: To study the clinicopathological and genetic features of natural killer (NK)-cell enteropathy for better understanding of this rare disease and prevention of its misdiagnosis. Methods: Two cases of NK-cell enteropathy were diagnosed in the First Affiliated Hospital of Zhengzhou University, China from October 2017 to February 2021. The clinical characteristics, morphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization and T cell receptor gene rearrangement were analyzed. The patients were followed up by a telephone interview. Results: The patients were both male, aged 40 and 28 years, respectively. Both patients were admitted to the hospital for an annual checkup without obvious gastrointestinal symptoms. The endoscopy showed that the gastric body of case 1 had a mucosal bulge, small area of congestion and erosion, while the rectum of case 2 had congestion and erosion. Microscopically, the lesions of the 2 cases were relatively limited. Many lymphoid cells infiltrated within the lamina propria of the mucosa and into the muscularis mucosa in case 2. In case 1, the glands were reduced in the lesion, and the glandular cavity was slightly compressed and deformed. There was no infiltration or destruction of the glands in either case. Lymphoid cells were atypical, with medium-to-large cell sizes. Their cytoplasm was medium-to-slightly abundant and appeared eosinophilic or translucent. In case 2, characteristic eosinophilic granules were seen in the cytoplasm of a few cells. The nuclei in both cases were round, oval and irregular, with fine chromatin, inconspicuous nucleoli, and no mitotic figures were noted. Necrosis was seen in case 1 while both cases had no central growth or destruction of blood vessels. Immunophenotyping showed that CD56, granzyme B and TIA-1 were positive in both cases, part of the cells was CD3-positive, and some cells were weakly CD4-positive in case 2. The CD5, CD8, CD30, ALK and B-lineage markers (CD20, CD79α) were all negative. The Ki-67 proliferation index was about 60% and 30%, respectively. Both cases were EBER negative. TCR gene rearrangement was polyclonal. Follow-up showed that none of the 2 patients had any special treatments and stayed well. Conclusions: NK-cell enteropathy is rare, with biological behaviors similar to benign tumors, and occasional recurrence. Its histology and immunophenotype are easily confused with NK/T cell-derived lymphomas. Combination of its unique endoscopic features, EBER negativity, polyclonal TCR gene rearrangement and good prognosis can confirm the diagnosis and avoid misdiagnosis and overtreatment.
Epstein-Barr Virus Infections ; Herpesvirus 4, Human/genetics* ; Humans ; Immunophenotyping ; Killer Cells, Natural ; Lymphoproliferative Disorders ; Male

OBJECTIVE: To investigate how the National Health Commission of China (NHCC)-recommended Chinese medicines (CMs) modulate the major maladjustments of coronavirus disease 2019 (COVID-19), particularly the clinically observed complications and comorbidities. METHODS: By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology (hyperinflammations, viral replication), complications (pain, headache) and comorbidities (hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search. RESULTS: Overall, 9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8 and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively. CONCLUSION The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.
COVID-19/physiopathology* ; Comorbidity ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine ; Medicine, Chinese Traditional ; SARS-CoV-2

Neonatal seizures are the most common clinical manifestations of critically ill neonates and often suggest serious diseases and complicated etiologies. The precise diagnosis of this disease can optimize the use of anti-seizure medication, reduce hospital costs, and improve the long-term neurodevelopmental outcomes. Currently, a few artificial intelligence-assisted diagnosis and treatment systems have been developed for neonatal seizures, but there is still a lack of high-level evidence for the diagnosis and treatment value in the real world. Based on an artificial intelligence-assisted diagnosis and treatment systems that has been developed for neonatal seizures, this study plans to recruit 370 neonates at a high risk of seizures from 6 neonatal intensive care units (NICUs) in China, in order to evaluate the effect of the system on the diagnosis, treatment, and prognosis of neonatal seizures in neonates with different gestational ages in the NICU. In this study, a diagnostic study protocol is used to evaluate the diagnostic value of the system, and a randomized parallel-controlled trial is designed to evaluate the effect of the system on the treatment and prognosis of neonates at a high risk of seizures. This multicenter prospective study will provide high-level evidence for the clinical application of artificial intelligence-assisted diagnosis and treatment systems for neonatal seizures in the real world.
Artificial Intelligence ; Electroencephalography/methods* ; Epilepsy/diagnosis* ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/diagnosis* ; Intensive Care Units, Neonatal ; Multicenter Studies as Topic ; Prospective Studies ; Randomized Controlled Trials as Topic ; Seizures/drug therapy*