ObjectiveTo observe the effects of modified Shaofu Zhuyutang on key proteins of the epidermal growth factor receptor （EGFR）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in SD rats with endometriosis. MethodsAfter successful establishment of an endometriosis model in 60 female SD rats of SPF grade via the auto-transplantation method， the rats were randomly divided into a model group， modified Shaofu Zhuyutang high-， medium-， and low-dose groups， and a gestrinone group， with another 12 rats serving as a blank group. The blank and model groups were administered 10 mL·kg^-1 normal saline， while the high-， medium-， and low-dose groups received 30， 15， and 7.5 g·kg^-1 modified Shaofu Zhuyutang， respectively. The gestrinone group was administered 0.25 mg·kg^-1 gestrinone suspension. After four weeks of treatment， uterine contractions were induced with 2 U of oxytocin， and the writhing response of rats was observed. After 24 h， the rats were euthanized， and the weight and volume of ectopic endometrial tissue were recorded. Hematoxylin-eosin （HE） staining was used to observe pathological changes in endometrial tissues， while the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay was used to evaluate the apoptosis rate of endometrial tissues. Immunofluorescence was used to detect the relative expression areas of the B-cell lymphoma-2 gene-associated promoter （Bad） and B-cell lymphoma-2 （Bcl-2） proteins in endometrial tissues. Serum levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， epidermal growth factor （EGF）， and EGFR were measured by enzyme-linked immunosorbent assay （ELISA）. The relative protein expression levels of EGFR， PI3K， phosphorylated PI3K （p-PI3K）， Akt， and phosphorylated Akt （p-Akt） in endometrial tissues were analyzed by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of EGFR， PI3K， and Akt. ResultsCompared with the blank group， the model group showed endometrial thickening， glandular and mesenchymal hyperplasia， a significant decrease in the relative expression area of Bad in ectopic endometrial tissues， a significant increase in the relative expression area of Bcl-2， and a significant reduction in the apoptosis rate as indicated by TUNEL staining. Serum levels of IL-1β， IL-6， TNF-α， EGF， and EGFR were significantly elevated （P<0.01）. The relative protein expression levels of EGFR， PI3K， p-PI3K， Akt， and p-Akt， as well as the mRNA expression levels of EGFR， PI3K， and Akt， were also significantly increased （P<0.01）. Compared with the model group， the high- and medium-dose groups of modified Shaofu Zhuyutang and the gestrinone group exhibited reduced glandular and mesenchymal hyperplasia to varying degrees， with dilated glandular lumens. The number of writhing responses was significantly reduced， the latency to writhing response was significantly prolonged， and the weight and volume of ectopic endometrial tissue were significantly decreased. The relative expression area of Bad in ectopic endometrial tissue was significantly increased， the relative expression area of Bcl-2 was significantly decreased， and the apoptosis rate was significantly elevated as shown by TUNEL staining. Serum levels of IL-1β， IL-6， TNF-α， EGF， and EGFR were significantly reduced， and the relative protein expression levels of EGFR， PI3K， p-PI3K， Akt， and p-Akt， as well as the mRNA expression levels of EGFR， PI3K， and Akt， were significantly decreased （P<0.05，P<0.01）. ConclusionModified Shaofu Zhuyutang may exert therapeutic effects on endometriosis by interfering with key proteins of the EGFR/PI3K/Akt signaling pathway and inducing apoptosis in ectopic endometrial tissue.

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

Studies have shown that rosacea is related to inflammatory factors, neurovascular function, micro-ecological environment and other factors. The Janus kinase (JAK) -signal transducer and activator of transcription (STAT) signaling pathway involves a variety of inflammatory cytokines, and plays an important role in cell proliferation, differentiation, apoptosis, angiogenesis and immune regulation. This review summarizes the JAK-STAT signaling pathway and explores its potential role in rosacea.

Objective:To summarize and review a Chinese family with cerebrotendinous xanthomatosis (CTX) so as to improve understanding of the disease.Methods:The proband was admitted to the Department of Neurology， the Second Hospital of Hebei Medical University on May 30, 2019. The medical history, neuro-imaging, pathology, CYP27A1 gene of the proband and CYP27A1 gene of her family were analyzed. Clinical features of similar cases from published literatures were retrieved and systematically summarized.Results:The proband was a 39-year-old female who was admitted to the Second Hospital of Hebei Medical University due to weakness of both lower limbs lasted for more than five years and aggravated for one year with speech slurred. The proband manifested with mental retardation, bilateral pyramidal tract impairment and cerebellar lesions, and had cholesterol crystal in xanthomas and compound heterozygous mutations of c.435G>A and c.1263+1G>A in CYP27A1 gene. The proband′s sister had the same mutation as the proband′s. The proband′s mother was the carrier of c.435G>A mutation, and father was the carrier of c.1263+1G>A mutation. Seventeen related cases concerning CTX with detailed clinical data were searched with major domestic databases. Combined with this case, clinical features with the frequency more than 50% were pyramidal sign, mental decline, ataxia, dysarthria, achilles tendon neoplasm, cataract, high arch foot.Conclusions:The onset of CTX is hidden, which can be diagnosed by its pathology and CYP27A1 gene detection. The possibility of CTX should be considered when there are unexplained clinical manifestations in common diseases such as pyramidal sign, mental decline, ataxia, dysarthria, achilles tendon neoplasm, cataract, high arch foot and so on.

Objective To evaluate the clinical efficacy of lymphoplasma exchange (LPE) for the treatment of severe refractory immune-related skin diseases.Methods From May 2013 to October 2015,8 patients with toxic epidermal necrolysis,drug-induced hypersensitivity syndrome (DIHS),pemphigus vulgaris,pemphigoid or paraneoplastic pemphigus were enrolled from Department of Dermatology,Xiangya Hospital,Central South University,who showed no response to conventional therapy or presented with multiple organ dysfunction.After the treatment with LPE,the efficacy was evaluated,and adverse reactions were observed.Results After one session of LPE therapy,6 patients received marked improvement,and were cured at last.In 1 patient with pemphigus vulgaris who was resistant to the treatment with high doses of glucocorticoids and immunosuppressive agents,the rashes regressed during the treatment with LPE,but recurred after the end of treatment.One patient with bullous pemphigoid presented with eruptive blisters on the next day after the treatment with LPE,which were considered as allergic reactions to allogeneic plasma.There were no obvious differences in white blood cell count,lymphocyte count,neutrophil count and blood platelet count in the peripheral blood of 8 patients before and after the treatment with LPE.During the follow-up of 3-5 years,all of the patients were recovered without recurrence,except 1 patient with bullous pemphigoid who died of disseminated tuberculosis after 1 year.Conclusion LPE is effective for the treatment of severe immune-related skin diseases,but attention should be paid to potential transfusion reaction and allergic reactions.

Objective To observe the effect of hyperbaric oxygenation (HBO) on apoptosis-inducing factor (AIF) and Caspase-3 levels in rats with permanent middle cerebral artery occlusion (MCAO),and to elucidate the apoptosis pathways.Methods Sixty Sprague-Dawley rats were subjected to permanent MCAO and then randomly divided into a control group and an HBO group,each of 30.Three hours later the rats of the HBO group were put into a hyperbaric cabin held at a pressure of 0.2 MPa for 9 hours.They inhaled supplementary oxygen at the 1st,3rd,5th,7th and 9th hour while the rats in the control group inhaled air at normal pressure.The neurological outcome was measured at the 3rd,13th and 72nd hour after the MCAO using Garcia scores.Apoptosis in the tissue of the ischemic penumbra,nuclear and mitochondrial AIF and Caspase-3 levels were measured at the 13th and 72nd hours after the modeling.Results The scores were significantly higher at the 13th hour than after the 3rd hour in both groups,and then even higher at the 72nd hour.Apoptosis was evident in the ischemic penumbra at the 13th and 72nd hours in both groups,but the number of cells was less at the 72nd hour than at the 13th hour in the control group.There was significantly less apoptosis in the HBO group than in the control group at the 13th hour.The average AIF level had significantly decreased in the nuclei and increased in the mitochondria by the 72nd hour compared with the 13th hour in both groups.The average levels of nuclear AIF at the 13th hour and the 72nd hour were lower than those in the mitochondria.But they were significantly higher in the HBO group than in the control group at the same time points.The levels of Caspase-3,normally zero,had increased by the 13th hour in both groups.The average level of Caspase-3 was significantly lower in both groups at the 72nd hour than at the 13th hour.Conclusions HBO can improve neurological function,inhibit the transfer of AIF from the mitochondria to the nucleus and reduce Caspase-3 levels.The mechanism may involve reducing apoptosis through caspase-dependent and caspase-independent pathways in the mitochondria.

OBJECTIVE:To investigate antitussive,antiasthmatic,phlegm-resolving and anti-inflammatory effects of Fritillaria cirrhosa and Fritillaria unibracteata. METHODS:Mice and guinea pig were randomly divided into blank control group (distilled water),ethanol extract groups,water extraction groups and powder groups of F. cirrhosa and F. unibracteata(1.13 g/kg for mice, 0.42 g/kg for guinea pig,calculated by crude drug),positive control group,with 10 mice(guinea pig)in each group. Each group was given relevant medicine intragastrically once a day for consecutive 5 d. Relative indicators were detected 30 min after last medication. The ammonia water induced cough method was used to investigate antitussive effect (dextromethorphan hydrobromide as positive drug,0.013 g/kg)by determining coughing latent period and coughing times within 3 min. After inducing asthma with 2％ histamine phosphate for 15 s, antiasthmatic effect (aminophylline as positive drug, 0.033 g/kg) was investigated by determining coughing latent period and the number of guinea pig with convulsive fall. The phenol red injection method was used to investigate phlegm-resolving effect (ambroxol as positive drug,21.304 g/kg) by determining the content of phenol red in the trachea of mice in phenol red expectoration test. The anti-inflammatory effect(dexamethasone acetate as positive drug,9.225×10-4 g/kg)was investigated by determining ear swelling degree and inhibition rate of ear swelling mice in xylene-induced inflammation test. RESULTS:Compared with blank control group, coughing latent period and cough induction latent period prolonged significantly in ethanol extract of F. cirrhosa and F. unibracteata groups,F. cirrhosa and F. unibracteata powder groups,positive control group, and coughing time decreased significantly within 3 min. The number of mice with convulsive fall decreased significantly in F. cirrhosa powder group, F. unibracteata ethanol group,F. unibracteata powder group and positive control group. The content of phenol red in the trachea of mice increased significantly,while ear swelling and inhibitory rate of ear swelling decreased significantly,with statistical significance (P<0.05 or P<0.01). There was no statistical significance in each index of mice between powder group and positive control group (P>0.05). Compared with corresponding groups of F. cirrhosa,coughing latent period of mice prolonged significantly in F. unibracteata ethanol extract group (P<0.05), other indexes had no statistical significance(P>0.05). CONCLUSIONS:The antitussive,antiasthmatic,phlegm-resolving and anti-inflammatory effects of F. cirrhosa are similar to or worse than those of F. unibracteata.

In order to compensate for the deficiencies of current medical education, improve the comprehensive quality of medical students, the First Clinical College, Tongji Medical College of Huazhong University of Science and Technology took the lead in carrying out the health management practice of rela-tives and friends, and made a beneficial exploration of humanistic education for medical students. Relatives and friends were regarded as the specific practice objects, and by telephone and network at school, face-to-face communication during the vacation, medical students established, managed and track the health records of relatives and friends. The students could practice while learning, which made medical students, in im-proving the knowledge structure, enhance their emotional communication with friends and relatives, improve their doctor-patient communication ability, establish the concept of humanistic care, and cultivate their occupation moral respect for life and their dedication to medicine and the sense of responsibility and mission to the society. It provides a new strategy for medical humanities education.

Objective:To investigate the effect of oxycodone hydrochloride on patients with analgesic effect and immune function of intestinal tumor after operation.Methods:50 patients with intestinal tumor from June 2014 to December 2016 who were treated in our hospital were selected randomly to divide into oxycodone group and fentanyl group with 25 cases in each group.Patients in oxycodone group were given oxycodone hydrochloride intravenous injection of 5mg 15 minutes before the end of surgery;and patients in fentany group were given fentany intravenous injection of 50ug 15 minutes before the end of surgery.Visual analogue scale (VAS),ramsey sedation score were observed at 3 h (T0),6 h (T1),12 h (T2),24 h (T3) 48 h (T4) after operation,Levels of serum tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6) and IL-10 CD4+,CD8+,CD4+/CD8+ and NK cells measured before anesthesia,and at T2,T3,T4 respectively.Results:At time point of T1,T2,Ramsey scores of oxycodone group were significantly lower than that of fentany group (P＜0.05),At time point ofT0,T3,T4,Ramsey scores of the two groups showed no significant difference (P＞0.05).At time point of T2,T3,T4,levels of serum TNF-α,IL-6 and IL-10 of two groups of patients were significantly higher than those of anesthesia before (P＜0.05),TNF-α,IL-6 and IL-10 ofoxycodone group was significantly lower than those of fentany group (P＜0.05).At time point ofT2,T3,T4,CD4+/at CD4+ of the two groups were significantly decreased,and CD8+ was significantly increased(P＜0.05).Levels of CD4+,CD4+/CD8+ of oxycodone group was significantly higher than that of fentany group (P＜0.05),and level ofCD8+ was significantly higher than that of fentany group.At time point of T2,T3,NK cells of two groups were significantly decreased,NK cells of oxycodone group were significantly higher than that of oxycodone group (P＜0.05).Differences among postoperative nausea,vomiting,respiratory depression,dizziness,skin itching incidence of two groups of patients were not statistically significant (P＞0.05).Conclusion:Oxycodone hydrochloride has little effect on the immune function of patients with intestinal tumor,and it is suitable for Postoperative analgesia of patients with intestinal tumor.

Objective To study the change of levels of IL-6,IL-17,IL-23,IL-8,TNF-α and IFN-γ and their clinical significance on children with different types of Henoch-Schonlein purpura (HSP) Methods The blood specimens of 180 children with HSP as disease group and 30 health children as normal group were collected respectively.Disease group included 30 children at acute stage and 30 at convalescence stage of primary abdominal type,30 at acute stage and 30 at convalescence stage of primary non-abdominal type,30 at acute stage of secondary abdominal type,and 30 at acute stage of secondary non-abdominal type.The plasma levels of IL-6,IL-8,IL-17,IL-23,TNF-α and IFN-γ in the two groups were measured by ELISA method for comparison and analysis.Results The plasma levels of IL-6,IL-8,IL-17,IL-23 and TNF-α in disease group were higher than those in the normal group (P＜0.05).Those levels in the children at acute stage and of primary group were also found to be higher than those at convalescence stage (P＜0.05) and of secondary group (P＜0.05) respectively.Comparison of IL-6,IL-8,IL-17,IL-23 and TNF-α between abdominal type and the non-abdominal type had no significant difference (P＞0.05).The plasma level of IFN-γ in disease group was lower than those in normal group (P＜0.05).The levels of IFN-γ in the children at acute stage and of primary group were lower than those at convalescence stage (P ＜0.05) and of the secondary group (P ＜0.05) Comparison of IFN-γ between abdominal type and non-abdominal type had no significant difference (P＞0.05) Conclusions The plasma levels of IL-6,IL-8,IL-17,IL-23,TNF-o,IFN-γ show obvious changes in children with HSP,which suggests that the changes of cytokines are associated with the pathogenesis and prognosis of Henoch-Schonlein purpura.