Heat stroke(HS)is a serious life-threatening disease caused by heat injury and characterized by a core body temperature>40℃with central nervous system dysfunction and multi-organ failure.The main pathophysiological manifestations of HS are the thermal acute phase response and thermoregulatory imbalance.Proteins are particularly sensitive to heat,and the thermal environment can cause massive protein denaturation,resulting in the deposition of unfolded and misfolded proteins in the cytoplasm,causing cellular dysfunction and even death.The unfolded protein response(UPR),mainly divided into the endoplasmic reticulum UPR and the mitochondrial UPR,is an important physiological process that helps proteins to fold correctly or degrade irretrievably denatured proteins.This paper summarizes the regulatory mechanisms of UPR,the relationship between UPR and severe diseases,as well as the relationship between HS and UPR to provide new ideas for the treatment of HS.

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.
Animals ; Mice ; Liver ; Aspartate Aminotransferases ; Bupleurum

OBJECTIVE: To investigate the role of tacrolimus-binding protein 38 (FKBP38) in follicle development and the mechanism by which Fkbp38 gene deletion causes premature ovarian insufficiency (POI). METHODS: The Cre-loxp system was used to construct oocyte-specific Fkbp38 knockout transgenic mice. The genotype of the transgenic mice was identified using PCR, and the expression of FKBP38 in the oocytes was verified. The numbers of primordial follicles, primary follicles, secondary follicles and antral follicles in Fkbp38 knockout mice and non-transgenic littermate control mice were counted with HE staining under a microscope for analyzing the effect of Fkbp38 deletion on follicular development. The fertility and serum sex hormone levels of the mice were determined by reproduction experiments and ELISA to assess ovarian function. Ovarian granulosa cell apoptosis of the mice was assessed using TUNEL assay. The activity of the downstream target protein of phosphorylated ribosomal S6 (PS6) of mTOR signaling pathway was detected, and the expressions of BCL-2 and BAX proteins were determined using immunofluorescence assay for assessing oocyte development in the mice. RESULTS: The oocyte-specific Fkbp38 knockout transgenic mouse model was successfully constructed, which showed decreased fertility, disordered sex hormone levels, and significantly reduced primordial follicles, primary follicles and secondary follicles in the ovary (P < 0.05), demonstrating POI-like changes. Compared with the control mice, oocyte-specific Fkbp38 knockout caused activation of the mTOR signaling pathway, significantly increased apoptosis of the granulosa cells, and obviously increased the BAX/BCL- 2 ratio by increasing BAX expression and reducing BCL-2 expression in the oocytes (P < 0.05). CONCLUSION FKBP38 plays an important role in follicle development, and Fkbp38 gene deletion in mice causes POI possibly by activating the mTOR signaling pathway and inducing granulosa cell apoptosis.
Female ; Humans ; Mice ; Animals ; Primary Ovarian Insufficiency/genetics* ; Apoptosis ; Signal Transduction ; Proto-Oncogene Proteins c-bcl-2 ; Granulosa Cells ; Mice, Transgenic ; Mice, Knockout ; TOR Serine-Threonine Kinases

OBJECTIVE: To study the clinical features of severe type 7 adenovirus pneumonia in children. METHODS: A retrospective analysis was performed for the clinical data of children who were diagnosed with severe type 7 adenovirus pneumonia from February to June, 2019. RESULTS: Among the 45 children, the male/female ratio was 3:2 and the median age was 14 months. All children had repeated fever, cough, and pulmonary moist rales, and the mean duration of fever was 14±4 days. The median time from fever to dyspnea was 8 days, and the time from fever to mechanical ventilation was 11.6±2.5 d. There was no significant increase in white blood cell count, with neutrophils as the main type. There were slight reductions in hemoglobin and albumin, while platelet and fibrinogen remained normal. There were increases in aspartate aminotransferase, lactate dehydrogenase, procalcitonin, and C-reaction protein. The detection rate of mixed pathogens was 84%. Effusion in both lungs was the major change on chest imaging (64%). Bronchoscopic manifestations were endobronchitis, tracheomalacia, and plastic bronchitis. The incidence rate of respiratory complications was 100%, and extrapulmonary complications mainly involved the circulatory system (47%), digestive system (36%), and nervous system (31%). Among the 45 children, 16 were administered with 400 mg/kg intravenous immunoglobulin (IVIG) daily for 5 days, with a mean duration of fever of 16±5 days, and 29 were administered with 1 g/kg IVIG daily for 2 days, with a mean duration of fever of 13±4 days; there was a significant difference in the mean duration of fever between the two groups (P=0.046). The overall mortality rate was 11%. CONCLUSIONS Severe type 7 adenovirus pneumonia in children has severe conditions, with a high incidence rate of complications and a high mortality rate, so it should be diagnosed and treated as early as possible.
Adenoviridae ; Bronchitis ; Female ; Fever ; Humans ; Infant ; Male ; Pneumonia, Viral ; Retrospective Studies

Objective To evaluate the effect of Oncomelania hupensis snail control of cutting the beach group in the south of Shaobo Lake. Methods The general situation of the project of cutting the beach was surveyed, and the snail distribution was surveyed and the results were compared before and after cutting the beach in the beach group. Results The area of cutting beach was 928.33 hm², the cubic meter of earthwork was 1 717.00 m³, the area of dumping ground was 425.76 hm², the beach surface elevation was 3.2 m after cutting the beach, and the beach surface was fallen to 1.0 m under the ordinary water level. The area with snails was 44.69 hm² before cutting the beach in 2011 but the area with snails was 1.78 hm² after cutting the beach in 2018. The area with remaining snails was declined by 96.02% in 2018 as compared with that in 2011, and surviving snails were distributed on the uncut beach face. Conclusion In Shaobo Lake, the O. hupensis snail breeding environment is eliminated by raising or lowering the beach, so it is an effective measure of snail control in lake regions.

OBJECTIVETo explore the anti-myeloma effect of suberoylanilide hydroxamic acid (SAHA) and on mouse myeloma cell line SP2/0 in vitro and in vivo and its mechanism.

METHODSThe inhibitory effect of SAHA on SP2/0 cells was measured by CCK-8 assay,and the apoptosis and cell cycle were analyzed by flow cytometry FACS. The protein expression of Caspase-3 and p53 of SP2/0 cells treated with SAHA were examined by Western blot. Annexin V/7-AAD double staining was performed to detect the apoptosis of SP2/0 induced by SAHA in vitro. SP2/0 cells (1×10) resuspended in 200 µl PBS were inoculated subcutaneously and intravenously into BALB/c mice, so as to establish aggressive or non-aggressive myeloma-bearing mouse models respectively. On day 3 after modeling, mice received SAHA or vehicle control treatment by intraperitoneal injection. The dose of SAHA was 60 mg/kg·d, 5 times a week for 3 weeks.

RESULTSIn SAHA-treated SP2/0 cells, the proliferation inhibition rate and apoptotic cells increased in a dose dependent manner. Also, SAHA significantly increased the ratio of cells in G phase and decreased in S phase. Molecular mechanisms of apoptosis and cell cycle arrest of SP2/0 induced by SAHA partly correlated with up-regulating the expression level of Caspase-3 and p53. In the non-aggressive myeloma-bearing mice, SP2/0 cells disappeared in peripheral blood after SAHA treatment. In the aggressive myeloma-bearing mice, inhibition of tumor growth and prolongation of the cell survival were observed after SAHA treatment.

CONCLUSIONSAHA inhibited SP2/0 cell proliferation, this effect associates with inducing apoptosis and cell cycle arrest, the mechanism of SAHA ralates partly with activating Caspase-3 and p53 pathway.

Animals ; Antineoplastic Agents ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Mice ; Mice, Inbred BALB C ; Multiple Myeloma

Madelung deformity is a rare deformity of forearm and wrist caused by growth disorders of distal radius ulnar and palmar epiphyseal. Current studies showed that its incidence mainly associated with trauma, epiphyseal developmental abnormalities, nutritional disorders and genetic deletion or mutation. The early clinical presentation is not typical, in middle and late time, wrist deformity and weak can appear. Plain film considered as the main means of diagnosis is often lack of early diagnosis significance. Although wrist joint magnetic resonance imaging showing early soft tissue and skeletal abnormalities were used for the early diagnosis of the disease, current domestic study in magnetic resonance imaging of this deformity is less. According to the size of the distal ulnar inclination angle and palm angle, this deformity can be divided into different types. The patients with severe deformity and symptoms usually need surgical intervention including ulna revision and osteotomy of the distal radius at present. Although the two operation can achieve good clinical results, the surgical trauma, infection and postoperative risk of joint activities are more.

Objective To study the L-carnosine induced apoptosis of human hepatocellular carcinoma HepG2 cells and its mechanism.Methods Human hepatocellular carcinoma HepG2 cells were cultured in vitro,then the cells in logarithmic phase were divided into 5 mM,20 mM,50 mM L-carnosine group and control group,treated with 5 mM,20 mM,50 mM L-carnosine and saline respectively.The proliferation of HepG2 cells was measured by CCK-8 assay after 24 hours and 48 hours treatment.The cell apoptosis and cell cycle were detected by flow cytometry after 48 hours treatment.The protein expression of Caspase-8,PI3K and Akt were detected by Western blot in each group after 48 hours treatment.Results CCK-8 and flow cytometry assay showed that both 20 mM and 50 mM L-carnosine treated group significantly inhibited the proliferation of HepG2 cells after 24 hours and 48 hours,and the inhibition were in a time and dose-dependent manner.Western blot revealed that the expressions of PI3K and Akt were down-regulated with the increase of L-carnosine concentration,while the expression of Caspase-8 was increased.Conclusion L-carnosine exhibits an inhibitory effect of the proliferation and promote apoptosis of human liver cancer cell line HepG2.The mechanism may be associated with the inhibition of the PI3K/Akt signaling pathway and activation of Caspase-8 signaling pathway.

PURPOSE: The objective was to determine the characteristics and prognostic factors of 86 Chinese patients with trisomy 8 aberrations and compare the prognostic value of International Prognostic System (IPSS) and Revised IPSS (IPSS-R) in this cohort. MATERIALS AND METHODS: A total of 86 cases diagnosed with primary myelodysplastic syndromes (MDS) with isolated tr8 or with tr8 and other additional cytogenetic aberrations diagnosed and treated at the Union Hospital, Tongji Medical College of Huazhong University of Science and Technology between July 2002 and March 2013 were reviewed. RESULTS: The median survival of the entire group was 23.0 months, and acute myeloid leukemia (AML) developed in 43% (37/86) patients within the follow up time. The univariate analysis revealed that overall survival (OS) was correlated with age, thrombocytopenia, absolute neutrophil count, marrow blasts, cytogenetic status and red blood cell transfusion at diagnosis, and the multivariate analysis revealed that age, marrow blasts, cytogenetic status and transfusion dependence were independent parameters for the OS. The cytogenetic complexity and marrow blasts had the strongest impact on the AML transformation by multivariate analysis. Comparing the two prognostic systems, both two systems could successfully discriminate risk groups for survival. IPSS-R was more refined than IPSS for predicting OS, but had no advantage in predicting the risk of AML development. CONCLUSION: This study confirmed the influence of clinical factors on the prognosis of 86 Chinese MDS patients with trisomy 8. In addition, IPSS-R can further refine prognostic discrimination in the IPSS risk categories.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group/*genetics ; Chromosome Aberrations ; Chromosomes, Human, Pair 8 ; Disease Progression ; Female ; Humans ; Leukemia, Myeloid, Acute/*genetics ; Male ; Middle Aged ; Multivariate Analysis ; Myelodysplastic Syndromes/*ethnology/*genetics ; Prognosis ; Retrospective Studies ; *Trisomy

OBJECTIVETo compare clinical features and therapeutic response of patients with aplastic anemia with and without cytogenetic abnormalities.

METHODSClinical features of 133 patients with successful chromosomal analysis were retrospectively studied, and therapeutic response between patients with and without cytogenetic abnormalities was compared.

RESULTSCytogenetic abnormalities were found in 9 patients, which included trisomy 8 (4 cases), monosomy 7 (2 cases) and Xq- (1 case), 1q- (1 case) and 7q- (1 case). No significant difference was detected between patients with or without cytogenetic abnormalities in terms of age (50 vs. 58, P=0.337), sex ratio (male 55.56% vs. 62.10%, female 44.44% vs. 37.90%, P=0.762), or episode of acute aplastic anemia (44.44% vs. 37.10%, P=0.728). Patients with cytogenetic abnormalities had a tendency towards poorer rate of therapeutic response, which was however not significantly different from those without (55.56% vs. 79.03%, P=0.116). All of the 4 patients with +8 responded to treatment, whilst none of those with -7 or 7q- did.

CONCLUSIONNo significant difference was found between aplastic anemia patients with or without cytogenetic abnormalities in terms of clinical features and therapeutic response. Patients with trisomy 8 seem to have a favorable response towards treatment.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; genetics ; therapy ; Child ; Chromosome Aberrations ; Female ; Humans ; Karyotyping ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult