Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Hyperthyroidism has a significant effect on the cardiovascular-metabolic system.Accumulating studies have confirmed that thyrotoxicosis is directly involved in vascular endothelial injury,inflammatory response,micro-vascular dysfunction,myocardial remodeling and other pathological processes,resulting in more severe coronary ar-tery stenosis,thrombus burden,and vasospasm in hyperthyroid patients.Combined to the complex complications and the special treatment of hyperthyroidism,the diagnosis and treatment of coronary artery disease is more diffi-cult.This review mainly summarizes the research progress of hyperthyroidism related coronary artery disease in re-cent years,aiming to guide clinicians to provide more precise management strategies for this population while consid-ering both endocrine and cardiovascular pathology.

Hyperthyroidism has a significant effect on the cardiovascular-metabolic system.Accumulating studies have confirmed that thyrotoxicosis is directly involved in vascular endothelial injury,inflammatory response,micro-vascular dysfunction,myocardial remodeling and other pathological processes,resulting in more severe coronary ar-tery stenosis,thrombus burden,and vasospasm in hyperthyroid patients.Combined to the complex complications and the special treatment of hyperthyroidism,the diagnosis and treatment of coronary artery disease is more diffi-cult.This review mainly summarizes the research progress of hyperthyroidism related coronary artery disease in re-cent years,aiming to guide clinicians to provide more precise management strategies for this population while consid-ering both endocrine and cardiovascular pathology.

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

The aim of this study was to establish an efficient and stable mouse model of hyperuricemic nephropathy (HN) by testing different modes of administration of potassium oxonate (PO) combined with hypoxanthine (Hx). Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guangdong Pharmaceutical University. Male C57BL/6 mice were randomly divided into a control group, a PO+Hx group (i.g.; 100 mg·kg^-1·d^-1 and 500 mg·kg^-1·d^-1, respectively), and a PO+Hx group (i.p.; 100 mg·kg^-1·d^-1, and 500 mg·kg^-1·d^-1). This HN model was induced by combination of PO and Hx administration once daily for 21 days. The results of serum biochemistry showed that the levels of serum creatinine and 24 h albuminuria were increased compared with the normal group in intragastric administration of PO combined with Hx (P < 0.05), but there was no significant difference in serum uric acid and hepatic levels of xanthine oxidase. The maximum value of serum uric acid and creatinine was 349.3 μmol·L^-1 and 26.4 μmol·L^-1, respectively, in mice injected with PO combined with Hx. The levels of liver xanthine oxidase and 24 h albuminuria were significantly increased in mice injected with PO combined with Hx (P < 0.01). Pathological data showed that renal tubules were dilated, the epithelial cells of renal tubules were disordered, and the production of collagen fibers, reactive oxygen species (ROS) and lipid peroxidase 4-hydroxynonenal (4-HNE) were slightly increased after intragastric administration of PO combined with Hx mice. Obvious infiltration of inflammatory cells and large area of collagen deposition, with a large amount of ROS and the lipid peroxide 4-HNE were produced in mice injected with PO combined with Hx. Western blot analysis showed that the expression of fibronectin (FN) and urate transporter 1 (URAT1) was increased after intragastric administration of PO combined with Hx in mice and further increased in mice injected with PO combined with Hx. This study demonstrates that injection with 100 mg·kg^-1 potassium oxonate combined with 500 mg·kg^-1 hypoxanthine establishes a stable and efficient mouse HN model.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective: To compare the effects between second toe tibial dorsal artery flap (2-TDAF) and second toe tibial plantar proper artery flap (2-TPPAF) in repairing finger skin and soft tissue defects. Methods: A retrospective cohort study was conducted. From January 2019 to June 2020, 27 patients with skin and soft tissue defects at the fingertips with area of 1.5 cm×1.2 cm-2.6 cm×1.8 cm after debridement who met the inclusion criteria were admitted to Suzhou Ruihua Orthopaedic Hospital, including 21 males and 6 females, aged 19-59 (37±10) years. According to flap repair methods used in the defective fingers, the patients were divided into 2-TDAF group (12 cases) and 2-TPPAF group (15 cases). The area of 2-TDAF ranged from 1.5 cm×1.2 cm to 2.5 cm×1.6 cm, and the area of 2-TPPAF ranged from 1.7 cm×1.3 cm to 2.6 cm×1.8 cm. Full-thickness skin grafts from the medial side of the ipsilateral leg were grafted to the wounds in donor sites, and the wounds in donor sites of skin grafts were directly sutured. Flap arterial diameter, flap excision time, flap survival situation of patients in 2 weeks after operation, and follow-up time were recorded. At the last follow-up, the two-point discrimination distance of flap graft site, total action motion (TAM) of the finger joints, and wound healing of the flap donor site were recorded; the Vancouver scar scale (VSS) was used to score the scar in donor area of the second toe and the recipient area of fingers; the appearance and self-satisfaction subscales of the Michigan hand outcomes questionnaire (MHQ) were used to evaluate the affected finger. Data were statistically analyzed with independent sample t test or Fisher's exact probability test. Results: The flap artery diameter of patients in 2-TDAF group was 0.35-0.80 (0.56±0.14) mm and the flap cutting time was (14.0±2.7) min, which were significantly shorter than 0.80-1.35 (1.02±0.16) mm and (19.7±3.4) min in 2-TPPAF group (with t values of 7.81 and 4.79, respectively, P<0.01). The flaps of patients in the 2 groups in recipient areas survived well in 2 weeks after operation, and the wounds in donor areas of flaps of patients in the 2 groups healed well at the last follow-up. There was no statistically significant difference in the postoperative follow-up time, and two-point discrimination distance of flap graft site, TAM of the finger joints, VSS score of scar in the second toe donor site and the finger recipient site, and the appearance and self-satisfaction of MHQ scores of the affected finger at the last follow-up (P>0.05). Conclusions: Compared with 2-TPPAF, 2-TDAF has a shallower anatomical layer and shorter time for surgical flap removal, which can preserve the proper arteries and nerves at the base of the toes and reduce the damage to the donor site.
Male ; Female ; Humans ; Soft Tissue Injuries/surgery* ; Finger Injuries/surgery* ; Cicatrix/surgery* ; Plastic Surgery Procedures ; Retrospective Studies ; Treatment Outcome ; Surgical Flaps ; Skin Transplantation ; Toes/surgery* ; Arteries ; Perforator Flap

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate

To investigate the prevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in quest and fed ticks in Yanbian area,Jilin province,we collected ticks from 8 counties (cities) from Yanbian area and submitted to test through real time RT-PCR targeting M segment of SFTSV after morphological identification.Bi-directional sequencing were also performed on the amplicons to conduct phylogenetic analysis.As the results,from April to September 2016,a total of 3 446 ticks,including 763 Dermacentor silvarum,222 Haemaphysalis concinna,639 Hae.japonica,515 Hae.longicornis,1 014 Ixodes persulcatus,were harvested.Among 1 605 ticks tested,the minimal infection rate was 8.65% for Hae.concinna,4.53% for Hae.japonica,1.59% for Hae.longicornis,and 3.2% for Haemaphysalis spp.respectively.Sequence analysis from 1 pool of Hae.longicornis showed that M segment of the SFTS viruses shares highly homologous (99%) with those isolated from patients in other provinces of China.Phylogenetic analyze showed that the SFTSV belongs to the same branch with those isolated from patients in Zhejiang Province (2012),and from Hae.longicornis infested on patients in Korea (2013) The SFTS virus obtained from Hae.longicornis in Yanbian area,Jilin,was proposed as YBHC-tick1-Jilin/China.

OBJECTIVE: To understand the general awareness of the residents around a newly built nuclear power,to evaluate the safety and the attitude on the construction of nuclear power. METHODS: By the stratified random sampling method,1 029 general publics and 260 representatives were selected for investigation. The participants were from 30 km range around the nuclear power plant,each 5 km was assigned as 1 layer and there were total 6 layers. RESULTS: 74. 9%( 965 /1 289) interviewees were not aware of nuclear power,3. 1%( 40 /1 289) interviewees were well or very-well understand nuclear power. The awareness score of the general publics was lower than that of the representatives( 1. 0 vs3. 0,P < 0. 01); male,younger people,higher educational level,higher family income,religious people and living close to the nuclear power plant had higher awareness( P < 0. 05). A total of 28. 4%( 366 /1 289) interviewees considered the nuclear power was very safe or safe. The evaluation of nuclear power safety of the general publics was inferior to the representatives( P < 0. 05). The representatives,older people and those living far away from the nuclear power have better evaluation on the nuclear power safety than the general publics( P < 0. 05). Only 13. 0%( 167 /1 289) interviewees supported building the nuclear power in their residence construction; male,people with family members working in nuclear power plant,people with high degree of awareness on nuclear power,considered highly safety of the nuclear power had higher support for the local nuclear power construction( P < 0. 05). The interviewees who mostly believe about nuclear energy sources were experts,government officials,plant management and domestic media. CONCLUSION: Residents around the nuclear power plant had low awareness of the knowledge about nuclear power. Therefore,it is necessary to enhance the awareness of residents on nuclear power and the trust on the government.