Porphyromonas gingivalis-induced hematogenous disseminated severe pneumonia: a case report.

Porphyromonas gingivalis, a gram-negative oral anaerobe among more than more than 500 bacterial species that colonizing the oral cavity, is involved in the pathogenesis and prototypic polybacterial consortium of periodontitis. It is mainly found in oral infections and rarely present in other organ diseases. Here, we describe a 43-year-old man with underlying diabetes who developed hematogenous disseminated severe pneumonia after P. gingivalis had invaded the blood. Next-generation sequencing of early alveolar lavage fluid and blood samples confirmed the diagnosis. The patient's lung infection improved after targeted antimicrobial treatment. He was successfully weaned from ventilatory support and transferred to the general ward. This case illustrates bacterial entry into the bloodstream of a patient with diabetes who had periodontal disease but did not maintain oral hygiene, leading to severe pneumonia. Periodontal disease is often ignored by the public, and it is difficult for critical care physicians to link severe pneumonia with periodontal disease. Thus, this case represents an important warning to critical care clinicians.

BTNL2 promotes colitis-associated tumorigenesis in mice by regulating IL-22 production.

Interleukin 22 (IL-22) has an important role in colorectal tumorigenesis and many colorectal diseases such as inflammatory bowel disease and certain infections. However, the regulation of IL-22 production in the intestinal system is still unclear. Here, we present evidence that butyrophilin-like protein 2 (BTNL2) is required for colorectal IL-22 production, and BTNL2 knockout mice show decreased colonic tumorigenesis and more severe colitis phenotypes than control mice due to defective production of IL-22. Mechanistically, BTNL2 acts on group 3 innate lymphoid cells (ILC3s), CD4+ T cells, and γδ T cells to promote the production of IL-22. Importantly, we find that a monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice and that the mBTNL2-Fc recombinant protein has a therapeutic effect in a dextran sulfate sodium (DSS)-induced colitis model. This study not only identifies a regulatory mechanism of IL-22 production in the colorectal system but also provides a potential therapeutic target for the treatment of human colorectal cancer and inflammatory bowel diseases.

Clinical and fundus imaging features of acute macular neuroretinopathy associated with COVID-19 / 中华眼底病杂志

Objective:To observe the clinical and fundus imaging features of acute macular neuroretinopathy (AMN) associated with COVID-19.Methods:A retrospective case study. A total of 32 eyes of 18 patients diagnosed of AMN associated with COVID-19 at Chengdu Aidi Eye Hospital from December 2022 to February 2023 were included. All patients had a history of fever 1 to 5 days prior to ocular onset and tested positive for SARS CoV-2 antigen. All patients were examined by best-corrected visual acuity (BCVA), color fundus photography, scanning laser ophthalmoscope (SLO), infrared fundus photography (IR), and optical coherence tomography (OCT); OCT angiography, visual field and multifocal electroretinogram (mf-ERG) were performed in 6 patients (11 eyes), 3 patients (6 eyes) and 1 patient (2 eyes), respectively. Follow-up time was 8-10 weeks. The clinical and fundus imaging features were observed and analyzed.Results:There were 6 males (12 eyes) and 12 females (20 eyes), aged from 15 to 36 years, with the mean age of (28.00±5.86) years. Fourteen patients were bilateral and 4 patients were unilateral. The time from the onset of eye symptoms to seeing a doctor was ranged from 1 day to 8 weeks. Among them, 6 patients (10 eyes) visited the doctor within 3 days of onset, while 12 patients (22 eyes) visited the doctor after 3 days of onset. The BCVA was 0.80±0.29. Fundus color photography and SLO examination showed that only 2 patients (4 eyes) showed sheet or petal-like dark red lesions in the macular area, and no obvious abnormal changes were observed in other patients. No obvious abnormalities were found in AF examination of all patients. IR examination showed no significant abnormality in 6 cases which came to hospital within 3 days after the onset, but irregular hyporeflective dark shadow lesions in the macular region of patients with more than 3-day course of disease was observed. OCT examinations of all eyes showed hyperreflective band or patchy lesion on the outer plexiform layer (OPL) and outer nuclear layer (ONL) and affect the ellipsoid zone (EZ) and interdigitation zone (IZ). In 11 eyes of 6 patients undergoing OCTA examination, the blood flow density of the choroidal capillary layer in the focal area decreased. In 6 eyes of 3 patients who underwent visual field examination, the physiologic scotoma was slightly enlarged. One patient (2 eyes) receiving mf-ERG showed a concave reduction in macular center amplitude. The hyperreflective band lesion on OPL and ONL disappear rapidly within 2 weeks, while the continuity of EZ recovered slowly, and the disruption of IZ kept existing for more than 10 weeks.Conclusions:Most AMN associated with COVID-19 are young women; IR showed irregular weak reflex in the lesion area. OCT showed strong OPL and ONL reflection. OCTA was characterized by decreased blood flow density in the choroidal capillary layer of the focal area.

Causes and prognosis analysis of hyperdynamic left ventricular ejection fraction in intensive care unit patients with sepsis / 中华危重病急救医学

Objective:To analyze the causes of hyperdynamic left ventricular ejection fraction (LVEF) in sepsis patients in the intensive care unit (ICU) and its impact on prognosis.Methods:A retrospective cohort study was conducted. The clinical data of 273 sepsis patients admitted to the department of critical care medicine of the Affiliated People's Hospital of Jiangsu University from January 2018 to October 2021 were collected including gender, age, severity score, comorbidities, source of infection, vital signs, transthoracic echocardiographic (TTE) parameters, fluid intake and output, vasoactive drug dose, therapeutic measures and prognostic indicators. The patients were divided into normal LVEF group (LVEF 0.55-0.70), low LVEF group (LVEF < 0.55) and hyperdynamic LVEF group (LVEF > 0.70) according to the TTE examination results within 7 days of ICU admission. The clinical indicators among the three groups were compared and analyzed, and multivariate Logistic regression analysis was used to screen risk factors for the development of hyperdynamic LVEF in patients with sepsis. Spearman correlation analysis was used to determine the correlation between the mortality of different types of LVEF and clinical variables.Results:Among 273 patients, 20 patients with severe valvular or cardiomyopathy at admission and those who did not completed cardiac ultrasound within 7 days of ICU admission were excluded. A total of 253 patients were finally enrolled, including 169 patients in the normal LVEF group, 40 patients in the low LVEF group, and 44 patients in the hyperdynamic LVEF group. There were statistically significant differences in age, sequential organ failure assessment (SOFA) score, central venous pressure (CVP), heart rate (HR), oxygenation index (PaO 2/FiO 2), blood lactate (Lac), urine output, vasoactive drug dose, ratio of hypertension, ischemic heart disease, chronic liver disease, cancer, invasive mechanical ventilation and renal replacement therapy (RRT), and incidence of septic shock among the different types of LVEF groups. TTE results analysis showed that the hyperdynamic LVEF group had higher stroke volume (SV) and cardiac index (CI) than those in the normal LVEF and low LVEF groups, lower systemic vascular resistance (SVR) than that in the normal LVEF and low LVEF groups, and an increased E/A ratio. The 90-day mortality in the hyperdynamic LVEF group was significantly higher than that in the normal LVEF and low LVEF groups [59.1% (26/44) vs. 24.9% (42/169), 32.5% (13/40), both P < 0.05]. Multivariate Logistic regression analysis showed that chronic liver disease [odds ratio ( OR) = 1.712, 95% confidence interval (95% CI) was 0.912-3.234, P < 0.001], cancer ( OR = 2.784, 95% CI was 1.296-6.151, P < 0.001), HR ( OR = 1.026, 95% CI was 1.014-1.038, P < 0.001), vasoactive drug dose ( OR = 1.133, 95% CI was 1.009-1.291, P < 0.001), and invasive mechanical ventilation ( OR = 2.141, 95% CI was 1.285-3.651, P < 0.001) were independent factors for hyperdynamic LVEF in ICU sepsis patients. Correlation analysis showed that the mortality of hyperdynamic LVEF, normal LVEF and low LVEF patients was positively correlated with vasoactive drug dose ( r value was 0.251, 0.361, 0.289, respectively, all P < 0.001). The mortality of the hyperdynamic LVEF patients was negatively correlated with SVR ( r = -0.545, P < 0.001). Conclusions:Chronic liver disease, cancer, HR, vasoactive drugs dose, and invasive mechanical ventilation are independent risk factors for hyperdynamic LVEF in patients with sepsis. Hyperdynamic LVEF is positively associated with mortality in sepsis patients, which may be due to the the decrease of SVR caused by septic vascular paralysis.

Epidemiological investigation of a foodborne illness outbreak caused by Vibrio parahaemolyticus contamination / 上海预防医学

ObjectiveIn this paper， the cause of an outbreak of foodborne disease in Huzhou City was analyzed， which may help avoid the recurrence of such incidents. MethodsThrough the field epidemiological investigation， the case definition was formulated and the questionnaire survey was carried out in the case group and the control group. In addition， the chi-square test and logistic regression method were used to identify the factors affecting the outbreak. The patient stool samples， food samples， environmental samples and water samples were collected and used for the laboratory test. The PFGE molecular typing was conducted on the isolated positive strains. ResultsThe number of people exposed during the same period was 410， and the number of possible cases was 18， with an incidence of 4.39%. Generally， the main symptoms were abdominal pain and diarrhea， accompanied by nausea， fatigue， fever and others. For case-control analysis， 17 of the 18 patients were included in the case group， and 19 non-patients were into control group. The results suggested that the risk factors were blanched deep-water shrimp（OR=19.42， 95%CI=1.06‒357.02， P=0.046）and steamed Ao Long （Australian lobster） with garlic and vermicelli （OR=22.01， 95%CI=1.24‒390.70， P=0.035）. According to the laboratory test results Vibrio parahaemolyticus （VP） was positive in 5 cases， and the serum type was is O10∶K4. In the reserved food， VP was positive in the samples of steamed Australian lobster with garlic vermicelli and lamb chops. The serum type was O5∶Kut. ConclusionThis incident was an outbreak of foodborne disease caused by the consumption of wedding food contaminated by VP. The dinner was served by Hotel B on September 17. Moreover， the suspicious foods include the blanched deep-water shrimp and steamed lobster with garlic vermicelli.

RNF186/EPHB2 Axis Is Essential in Regulating TNF Signaling for Colorectal Tumorigenesis in Colorectal Epithelial Cells.

The receptor tyrosine kinase EPHB2 (EPH receptor B2) is highly expressed in many human cancer types, especially in gastrointestinal cancers, such as colorectal cancer. Several coding mutations of the EPHB2 gene have been identified in many cancer types, suggesting that EPHB2 plays a critical role in carcinogenesis. However, the exact functional mechanism of EPHB2 in carcinogenesis remains unknown. In this study, we find that EPHB2 is required for TNF-induced signaling activation and proinflammatory cytokine production in colorectal epithelial cells. Mechanistically, after TNF stimulation, EPHB2 is ubiquitinated by its E3 ligase RNF186. Then, ubiquitinated EPHB2 recruits and further phosphorylates TAB2 at nine tyrosine sites, which is a critical step for the binding between TAB2 and TAK1. Due to defects in TNF signaling in RNF186-knockout colorectal epithelial cells, the phenotype of colitis-propelled colorectal cancer model in RNF186-knockout mice is significantly reduced compared with that in wild-type control mice. Moreover, we find that a genetic mutation in EPHB2 identified in a family with colorectal cancer is a gain-of-function mutation that promoted TNF signaling activation compared with wild-type EPHB2. We provide evidence that the EPHB2-RNF186-TAB2-TAK1 signaling cascade plays an essential role in TNF-mediated signal transduction in colorectal epithelial cells and the carcinogenesis of colorectal cancer, which may provide potential targets for the treatment of colorectal cancer.

Cancer cell-expressed BTNL2 facilitates tumour immune escape via engagement with IL-17A-producing γδ T cells.

Therapeutic blockade of the immune checkpoint proteins programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has transformed cancer treatment. However, the overall response rate to these treatments is low, suggesting that immune checkpoint activation is not the only mechanism leading to dysfunctional anti-tumour immunity. Here we show that butyrophilin-like protein 2 (BTNL2) is a potent suppressor of the anti-tumour immune response. Antibody-mediated blockade of BTNL2 attenuates tumour progression in multiple in vivo murine tumour models, resulting in prolonged survival of tumour-bearing mice. Mechanistically, BTNL2 interacts with local γδ T cell populations to promote IL-17A production in the tumour microenvironment. Inhibition of BTNL2 reduces the number of tumour-infiltrating IL-17A-producing γδ T cells and myeloid-derived suppressor cells, while facilitating cytotoxic CD8+ T cell accumulation. Furthermore, we find high BTNL2 expression in several human tumour samples from highly prevalent cancer types, which negatively correlates with overall patient survival. Thus, our results suggest that BTNL2 is a negative regulator of anti-tumour immunity and a potential target for cancer immunotherapy.

DOCK2 regulates antifungal immunity by regulating RAC GTPase activity.

Fungal infections cause ~1.5 million deaths each year worldwide, and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria. The major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant species. Therefore, a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic strategies. Here, we report that DOCK2 (dedicator of cytokinesis 2) promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in macrophages. DOCK2-deficient macrophages exhibit decreased RAC GTPase (Rac family small GTPase) activation and ROS (reactive oxygen species) production, which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling pathways. Mechanistically, after fungal stimulation, activated SYK (spleen-associated tyrosine kinase) phosphorylates DOCK2 at tyrosine 985 and 1405, which promotes the recruitment and activation of RAC GTPases and then increases ROS production and downstream signaling activation. Importantly, nanoparticle-mediated delivery of in vitro transcribed (IVT) Rac1 mRNA promotes the activity of Rac1 and helps to eliminate fungal infection in vivo. Taken together, this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of RAC GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA.

Metformin inhibits proliferation and promotes apoptosis of HER-2 positive breast cancer cells possibly through the Hippo-YAP pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of metformin on the proliferation and apoptosis of HER-2-positive breast cancer cell line SKBR3 and explore the possible mechanism of its action.@*METHODS@#SKBR3 cells were treated with different concentrations (20-120 μmol/L) of metformin, and the changes in cell proliferation and colony formation ability were assessed using CCK-8 assay and crystal violet staining, respectively. Flow cytometry was performed to analyze cell apoptosis and cell cycle changes. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect mRNA expressions of YAP, TAZ, EGFR, CTGF, CYR61, E-cadherin, N-cadherin, vimentin and fibronectin in the treated cells, and the protein expressions of YAP and TAZ were detected using Western blotting; immunofluorescence assay was used to observe YAP/TAZ nuclear translocation in the cells.@*RESULTS@#Metformin treatment significantly inhibited the proliferation of SKBR3 cells (P < 0.05) in a concentration- and time-dependent manner. The results of flow cytometry showed that metformin significantly promoted apoptosis and caused cell cycle arrest at G1 phase in SKBR3 cells. Metformin treatment significantly down-regulated the mRNA expressions of YAP, TAZ, EGFR, CTGF and CYR61, N-cadherin, vimentin and fibronectin (P < 0.05) and up-regulated the expression of E-cadherin (P < 0.05); Western blotting results showed that YAP and TAZ protein expressions were significantly down-regulated in the cells after metformin treatment (P < 0.05). Immunofluorescence assay revealed that metformin treatment caused the concentration of YAP and TAZ in the cytoplasm, and significantly reduced their amount in the cell nucleus.@*CONCLUSION@#Metformin can inhibit proliferation and promote apoptosis and epithelal-mesenchymal transition of HER-2 positive breast cancer cells possibly by that inhibing YAP and TAZ expression and their nuclear localization.

Anti-tumor mechanism of sesquiterpenoids from Cryptoporus volvatus based on molecular docking / 南方医科大学学报

OBJECTIVE@#To identify the target genes mediating anti-tumor effect of sesquiterpenoids from Cryptoporus volvatus and explore the possible mechanism using molecular docking and molecular dynamics simulation.@*METHODS@#Based on the chemical structure of sesquiterpenes from C. volvatus, we explored the online reverse target finding websites PharmMapper, SEA, Target Hunter and related literature for preliminary prediction of possible anti-tumor targets. Discovery Studio 4.0 (Libdock function) and Maestro 12.3 were used to connect sesquiterpenes with the possible targets, and the potential targets were selected according to the scores. The interaction between the sesquiterpenes and the targets were analyzed using 2D interaction diagram, and the influence of different sesquiterpene skeletons on their activity was inferred based on their activity measurements in experiment. Kinetic simulation was performed for front-end protein sequence (1UNQ) of the Akt (protein kinase B) and for the complex formed by 1UNQ and compound 4 (which had the best cytotoxic activity in vitro) in its optimal conformation, and the root mean square deviation (RMSD) value and root mean square float (RMSF) value of the complex and 1UNQ were measured to evaluate the stability of the binding of compound 4 to the target.@*RESULTS@#The sesquiterpenes showed optimal binding with 1UNQ. Analysis of 2D interaction diagram suggested that the hydrogen bonding and electrostatic force were the most important forces mediating the interaction between the sesquiterpenes and 1UNQ. Analysis of the optimal 3D conformation showed that for different sesquiterpenes, a slight change of the molecular framework produced a steric hindrance effect and caused changes in their bioactivity. Kinetic simulation showed that the complex formed by compound 4 and1UNQ had a lower RMSD than the target pure protein sequence, indicating that compound 4 could stably bind to 1UNQ. The anti-tumor effect of the sesquiterpenoids from C. volvatus was associated with their ability to cause Lys-144 acetylation, which blocks Akt binding to the downstream PIP3 and thus affects the proliferation of tumor cells.@*CONCLUSION@#1UNQ is the target of sesquiterpenoids from C. volvatus, which affects the proliferation of tumor cells by acetylating Lys-14.

SARS-CoV-2 vaccine research and immunization strategies for improved control of the COVID-19 pandemic / 医学前沿

The record speed at which Chinese scientists identified severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) and shared its genomic sequence with the world, has greatly facilitated the development of coronavirus disease (COVID-19) diagnostics, drugs, and vaccines. It is unprecedented in pandemic control history to develop a dozen successful vaccines in the first year and to immunize over half of the global population in the second year, due to the efforts of the scientific community, biopharmaceutical industry, and regulatory agencies worldwide. The challenges are both great and multidimensional due to the rapid emergence of virus variants and waning of vaccine immunity. Vaccination strategies need to adapt to these challenges to keep population immunity above the herd immunity threshold, by increasing vaccine coverage, especially for older adults and young people, and providing timely booster doses with homologous or heterologous vaccine boosts. Further research should be undertaken to develop more effective vaccines against SARS-CoV-2 variants and to understand the best prime-boost vaccine combinations and immunization strategies to provide sufficient and sustainable immune protection against COVID-19.

SARS-CoV-2 Restructures the Host Chromatin Architecture

SARS-CoV-2 has made >190-million infections worldwide, thus it is pivotal to understand the viral impacts on host cells. Many viruses can significantly alter host chromatin1, but such roles of SARS-CoV-2 are largely unknown. Here, we characterized the three-dimensional (3D) genome architecture and epigenome landscapes in human cells after SARS-CoV-2 infection, revealing remarkable restructuring of host chromatin architecture. High-resolution Hi-C 3.0 uncovered widespread A compartmental weakening and A-B mixing, together with a global reduction of intra-TAD chromatin contacts. The cohesin complex, a central organizer of the 3D genome, was significantly depleted from intra-TAD regions, supporting that SARS-CoV-2 disrupts cohesin loop extrusion. Calibrated ChIP-Seq verified chromatin restructuring by SARS-CoV-2 that is particularly manifested by a pervasive reduction of euchromatin modifications. Built on the rewired 3D genome/epigenome maps, a modified activity-by-contact model2 highlights the transcriptional weakening of antiviral interferon response genes or virus sensors (e.g., DDX58) incurred by SARS-CoV-2. In contrast, pro-inflammatory genes (e.g. IL-6) high in severe infections were uniquely regulated by augmented H3K4me3 at their promoters. These findings illustrate how SARS-CoV-2 rewires host chromatin architecture to confer immunological gene deregulation, laying a foundation to characterize the long-term epigenomic impacts of this virus.

The clinical efficacy of early application of fluconazole combined sodium bicarbonate in oral fungal infections in elderly patients with AECOPD / 中华急诊医学杂志

Objective:To investigate the efficacy of the combined application of fluconazole and sodium bicarbonate in treatment of oral fungal infections among elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:A total of 360 elderly patients with AECOPD treated in the Emergency Ward of our hospital during July 1, 2018 and December 31, 2019, were included for observation. After admission, the oral mucosal lesions were observed every day, and fungal smear and fungal culture were performed immediately once signs of fungal infection appeared. Meanwhile, fluconazole was given with 300 mg. oral. qd., followed by 150 mg. oral. qd., and 2.5% sodium bicarbonate was given three times a day as gargle.Results:The prevalence of oral fungal infection was 8.3% among which candida infection accounted for 83.2%. The mean treatment time was 5.0 ± 0.3 days. Daily observation of the oral cavity, early detection and application of fluconazole combined with sodium bicarbonate had significantly clinical effect in elderly AECOPD patients with oral fungal infection, with an effective rate of 16.7%, and a cure rate of 83.3%. No toxic side effects on liver and kidney function were found during the treatment. Obvious efficacy was found in relieving clinical symptoms, and there was no increase in hospitalization costs and time.Conclusion:Early combination of fluconazole and sodium bicarbonate has a significant clinical effect on control of oral fungal infection in elderly patients with AECOPD.

Discussion on Internet plus medical service in public hospitals / 中华医院管理杂志

With the continuous development of Internet related technology in recent years and the improvement of infrastructure such as software and hardware, Internet plus medical service has developed rapidly under the dual development dividends of market demand and national policy incentives. The authors analyzed the current situation and problems in the development of public hospitals′ Internet plus medical services, and explored how public hospitals combine the opportunity of " the 14th five-year plan" to achieve the optimization of Internet plus medical treatment through 4 aspects: system construction, information construction, hierarchical diagnosis and treatment, and new technology application.

Clinical analysis of 1 057 patients with critical illnesses in a dermatological ward / 中华皮肤科杂志

Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.

HSV-1 H129-Derived Anterograde Neural Circuit Tracers: Improvements, Production, and Applications / 神经科学通报·英文版

Anterograde viral tracers are powerful and essential tools for dissecting the output targets of a brain region of interest. They have been developed from herpes simplex virus 1 (HSV-1) strain H129 (H129), and have been successfully applied to map diverse neural circuits. Initially, the anterograde polysynaptic tracer H129-G4 was used by many groups. We then developed the first monosynaptic tracer, H129-dTK-tdT, which was highly successful, yet improvements are needed. Now, by inserting another tdTomato expression cassette into the H129-dTK-tdT genome, we have created H129-dTK-T2, an updated version of H129-dTK-tdT that has improved labeling intensity. To help scientists produce and apply our H129-derived viral tracers, here we provide the protocol describing our detailed and standardized procedures. Commonly-encountered technical problems and their solutions are also discussed in detail. Broadly, the dissemination of this protocol will greatly support scientists to apply these viral tracers on a large scale.

Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure-activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties.

Effects of a Reinforcing and Reducing Method of Acupuncture on Interstitial Fluid Pressure in Subcutaneous Tissue of Minipig / 医用生物力学

Objective To study the effect of the reinforcing and reducing method of acupuncture reported in first Chapter the Nine Needles and Twelve Yuan of the Miraculous Pivot on interstitial fluid pressure (IFP) in subcutaneous tissue of minipig, and to investigate its biomechanical mechanism of regulating the interstitial fluid. Methods Nine healthy minipigs were randomly selected for reinforcing method (pull or press) and reducing method (wave a big pinhole), and tested on soft skin tissues of the abdomen. The IFP in the normal state (NS), the low volume (LV) state (by extracting interstitial fluid) and the high volume (HV) state (by injecting saline solution) was measured before and after acupuncture. Results In the normal state, pulling and pressing the needle could obviously increase IFP, while reducing method could significantly decrease IFP, leading to a rapid decrease in 5 min after acupuncture. In the LV state, pulling and pressing the needle could increase IFP. However, in 10 min after acupuncture, the descend rates of IFP were relatively slower. In the HV state, the reducing method could significantly decrease IFP, and the changing trend in 5 min after acupuncture was different from that of the control group. Conclusions The reinforcing and reducing method of acupuncture could increase or decrease IFP, which proved that the acupuncture method could regulate IFP in the opposite direction. The research findings provide a new scientific basis for using reinforcing and reducing method of acupuncture in clinic.

Study of Gq mutations and their inhibitors in uveal melanoma / 药学学报

Uveal melanoma (UM) is one of most common ocular cancers and is extremely malignant; so far there is no effective treatment. Moreover, the survival period is only 2-7 months after metastasis. It has been proven that more than 83% of uveal melanomas harbor mutations in G protein subunit α q (GNAQ) or G protein subunit α 11 (GNA11), among which 95% are a Q209P/L single-site mutation. Q209P/L mutations lead to dysfunction of guanine triphosphatase (GTPase) in the G protein and result in constitutive activation of downstream pathways including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), Ras homologue (Rho)/ Rho-associated kinase (Rock)/Yes-associated protein (YAP) and others. Therefore, targeting GNAQ/GNA11 mutations are potential strategies for UM treatment. This review will focus on roles of G protein mutations in UM progression, and the potential therapeutic effects of GNAQ/GNA11 inhibitors, and will provide insights into basic and clinical research on UM treatment.

Self-management experience of family caregiver with dementia: a systematic review of qualitative studies / 中国实用护理杂志

Objective:To conduct a systematic review on the experience of family caregivers of dementia patients during self-management, so as to provide reference to offer targeted self-management intervention for the family caregivers.Methods:Five English ( MedLine, Embase, CINAHL, PsycINFO, Web of Science) and four Chinese (CBM, CNKI, WANFANG,VIP) databases were chosen to retrieval literatures on self-management experience of family caregivers of dementia patients from inception to October 31st ,2019. The JBI Critical Appraisal Tool for qualitative studies in Australia was used to evaluate the quality of studies. Integrating method was applied to integrate the results.Results:Totally 18 findings were extracted from 6 qualified studies, 7 new categories were generated and finally 2 synthesized results were obtained: obstacles to self-management: insufficient information and service support; neglect of physical health and social interaction; heavy economic burden; mental and emotional trauma. Promote self-management: self-adjusting emotions. Actively managing physical health. Seeking for help and support.Conclusion:The external support for self-management of family caregivers is actually needed. And support that aim to help caregivers overcome the obstacles of self-management and facilitate self-management should be provided from various ways.