Objective To investigate the characteristics of peripheral lymphocytic subsets and cytokines in patients with primary biliary cirrhosis( PBC) and their changes after therapy. Methods Eighty two patients with untreated PBC were divided randomly into three groups. Group U (28 patients) were treated with ursodeoxycholic acid ( UDCA) , group UP (27 patients) were treated with UDCA and prednisonlone, while group UA (27 patients) were treated with UDCA and azatharaprine. Levels of peripheral lymphocytic subsets and cytokines were monitored at 0, 3, 6 months after therapy. Twenty healthy people were included as healthy control ( HC). Results Compared with HC, the percentage of CD/ T cell (P = 0. 044) increased in PBC; the levels of IFNγ(P = 0. 001), IL-2 (P =0. 000) , IL-4 (P =0. 010) , IL-6 (P = 0. 029) , tumor necrosis factora ( TNFα ) ( P = 0. 000) , IL-1β ( P = 0. 008 ) and transforming growth factorβ(TGFβ) (P =0. 069) increased in PBC. The level of TNFa in peripheral was correlated with those of ALT (P=0.005), AST (P=0.002), total bilirubin(Tbil) (P=0.001), direct bilirubin( Dbil) (P=0. 002) , and mayo risk score(MRS) (P=0. 020). The percentage of CD_4~+T cell decreased in group U. In group U, the levels of IFNγ,IL-4,IL-6 all decreased after therapy at the third month, but rebounded thereafter. In group of UP and UA, the levels of IFN-γ, IL-4, IL-6 were suppressed below the levels of baseline after therapy.Levels of TNFa and IL-2 decreased in all three groups after therapy. Conclusions Levels of both Thl and Th2 related cytokines are abnormal in the peripheral blood of patients with PBC. The abnormal levels of Thl related cytokine indicated that PBC is a cell immunity based autoimmune disease. IFNγ,TNFα are directly related to the disease. The three treatments have different effects on the adjustment of the immune system.

There are three kinds of molecular targeted antitumor drugs: inhibitors of membrane?associated therapeutic targets, inhibitors of intracellular signaling pathways, and immunomodulators. Inhibitors of membrane?associated therapeutic targets include epidermal growth factor receptor inhibitors (EGFRIs), KIT and BCR?ABL inhibitors, antiangiogenic agents and multikinase inhibitors. Inhibitors of intracellular signals include inhibitors of the RAS?RAF?MEK?ERK pathway, PI3K?AKT?mTOR pathway and Hedgehog signaling pathway. Inhibitors of cytotoxic T lymphocyte associated?antigen(CTLA) and programmed death 1 (PD?1) belong to immunomodulatory agents. Cutaneous adverse effects of different molecular targeted antitumor drugs share some common features, but also differ from each other. Most of the side effects are dose?dependent and reversible. Management strategies should be adjusted according to the severity of skin eruptions. Dose tapering and even discontinuation of antitumor drugs are necessary for very severe cases, but for mild ones, symptomatic treatment might be enough. This article reviews cutaneous adverse reactions to molecular targeted therapy as well as their prevention and management.

The five flavours of traditional Chinese medicine(TCM)stand for five tastes,such as pungent,sweet,sour,bitter and salt.The five flavours not only stand for the actual tastiness of herbs,but also the effect characteristic of TCM according to traditional medical theory.So this kind of situation led to a disorder of the marking standardization of five flavours.So the authors think that we should mark herbs(or TCM)based on their true tastiness,and this way maybe help us to solve the problem and to research the relationship between the flavours and the effect of the herbs(or TCM).

Objective To report a case of toxic epidermal necrolysis associated with geotrichosis due to Geotrichum silvicola. Methods The exudates from the body surface, blood and urine of the patient were examined by microscopy and simultaneously inoculated onto the Sabouraud dextrose agar (SDA) medium. The isolate was examined by microscopy, PCR which amplified the D1/D2 domain of 26S rDNA, and gene sequencing. Homologous sequences were searched in the GenBank/EMBL/DDBJ/PD nucleotide sequence library, and the genetic relationship was analyzed with the genealogical tree. Results Microscopy of pus from the abscess on the dorsa of left hand revealed a lot of spores and a few hyphae, which were not observed in the blood or urine specimens. Meanwhile, whitish colonies were grown in all the three successive cultures of blood and urine specimens, rather than the exudates on the body surface. After itraconazole and garlicin were administered for one week, both microscopic exam and fungus culture were negative. Microscopic exam of the isolate showed arthrospores arranged in chains, budding spores and a few of hyphae. It was found that there was a one-base difference between our isolate (Hebei-1) and the isolate from kerion -like eruptions (Changzheng-1), and a four-base difference between our isolate and the reference Geotrichum silvicola strain as well, in the D1/D2 domain of 26S rDNA. This isolate was identified to be most close to Changzheng-1 in the phylogenetic tree. Conclusion The patient with toxic epidermal necrolysis is associated with geotrichosis due to Geotrichum silvicola.

Small scale restricted online course (SPOCs)+flipped classroomteaching is expected to become an important complement to the traditional teaching of dermatology. In this teaching mode, first of all knowledge nodes are divided separately according to the syllabus and for each node, 7 to 10 minutes of micro video or micro-lecture is made, which enables students to make best use of fragmented time through the network to master relevant knowledge independently before the trainee. In the flipped classroom, based on the difficulties and misunderstandings of learning reflected from the network monitor data, teacher can make full use of time on demonstrating typical cases, organizing discussion, grouping students to take diag-nostic and therapeutic exercise, answering targeted questions, teaching clinical thinking, experience and doctor-patient communication skills. Through this teaching mode, the new teaching idea can be imple-mented that students are in dominant position while teachers are in leading position, which contributes to deepening the understanding , absorption and application of knowledge and improving students' ability of communication, cooperation, diagnosis and treatment.

Objective To investigate the effects of liver X receptor (LXR) agonist on the proliferation of mouse pancreatic β cell line MIN6 cells.Methods The viability,changes of cell cycle,mRNA levels of S phase kinase associated protein 2 (Skp2) and p27,and protein levels of Skp2 and p27 in MIN6 cells treated with LXR agonist T0901317 were determined by the CCK-8 method,flow cytometry,real-time RT-PCR and western blot,respectively.Results The viability of MIN6 cells treated with 1 μmol/L,5 μmol/L and 10 μnol/L of T0901317 were (98.54 ±0.94)％,(87.03 ±0.93)％ and (75.57 ± 1.85)％ of the controls,respectively,and there was significant difference among them (F =301.90,P ＜ 0.01).The percentages of G1 phase cells in the MIN6 cells treated with 0 μmol/L,1 μmol/L,5 μmol/L and 10 μmol/L of T0901317 were (35.93 ±2.25)％,(38.45 ±0.91)％,(45.46±1.34)％ and (53.28 ± 1.14) ％,respectively,and there was significant difference among them (F =80.83,P ＜ 0.01).Similarly,the percentages of S phase cells in the MIN6 cells treated with 0 μmol/L,1 μmol/L,5 μmol/L and 10 μmoi/L of T0901317 were (52.87 ± 1.19) ％,(48.65 ± 0.85) ％,(36.31 ± 1.37) ％ and (31.45 ± 1.22) ％,respectively,and there was also significant difference among them (F =221.30,P ＜ 0.01).The protein levels of p27 in the MIN6 cells treated with 10 μmol/L of T0901317 (2.84 ± 0.14) were significantly higher than that in the controls (2.28 ± 0.10) (t =4.54,P ＜ 0.05),while there was no significant difference in the mRNA levels of p27 between them (t =0.28,P ＞ 0.05).However,10 μmol/L of T0901317 significantly decreased mRNA (0.52 ± 0.02,t =29.22,P ＜ 0.01) and protein levels (0.98 ± 0.12 vs 1.89 ± 0.01,t =10.98,P ＜ 0.01) of Skp2 in MIN6 cells.Based on the control siRNA transfection group as a reference (100％),the cell survival rates of the p27 siRNA transfection group,10 μmol/L of T0901317 treatment group and the intervention group (p27 siRNA transfection + T0901317 treatment) were (100.97 ± 1.08) ％,(75.03 ± 1.83) ％ and (86.67 ± 2.45) ％,respectively.There was no significant difference between the control siRNA and p27 siR-NA transfection groups (t =1.542,P ＞ 0.05).Compared with the control siRNA transfection group,the cell survival rates of the T0901317 treatment group decreased (t =23.58,P ＜ 0.01).There was also significant difference in the cell survival rates between the T0901317 treatment group and the intervention group (t =7.77,P ＜ 0.01).Conclusion The activation of LXR may induce pancreatic β cell cycle arrest by up-regulating the expression of p27 and down-regulating the expression of Skp2.

Objective:To analyze clinical features and prognosis of Mycoplasma pneumoniae-induced rash and mucositis (MIRM) . Methods:Among patients who were diagnosed with erythema multiforme/severe erythema multiforme or Stevens-Johnson syndrome at discharge from the First Affiliated Hospital, Sun Yat-sen University from November 2004 to May 2021, patients with MIRM were screened out according to diagnostic criteria for MIRM and after exclusion of other causes, and their clinical manifestations, laboratory and auxiliary examinations, treatment and prognosis were analyzed.Results:Eight patients were found to meet the MIRM diagnostic criteria, including 4 males and 4 females, with the age at onset being 15.63 ± 9.16 years (range, 4 - 30 years) . All the 8 patients had fever, and 5 of them had upper respiratory symptoms such as cough and sore throat. Oral mucosal damage occurred in all the patients, 5 of whom presented with blood crusts on the lips; eye damage occurred in 7 patients, which manifested as conjunctiva hyperemia and increased secretions. All the patients presented with skin lesions, including 5 with targetoid lesions and 4 with blisters. All the patients were serologically positive for anti- Mycoplasma pneumoniae IgM. One patient experienced recurrent upper respiratory tract infections such as dry cough, each episode was closely related to Mycoplasma pneumoniae infection, and whole exome sequencing of the peripheral blood showed heterozygous mutations in the NLRC4 and IRGM genes. Histopathological examination of skin lesions was performed in 3 patients, and the results were consistent with the diagnosis of erythema multiforme. Seven patients were treated with systemic glucocorticoids, 6 with intravenous immunoglobulin, 5 with azithromycin, and 5 with acyclovir, valacyclovir or ribavirin. After an average 2.9-year follow-up, 3 patients were cured, 1 was blind, 1 experienced recurrent dry cough, oral ulcers and rashes on the limbs, and the remaining 3 developed eye damage such as meibomian gland dysfunction, punctal stenosis and corneal epithelial damage. Conclusions:MIRM mostly occurred in children and young adults, and was mainly accompanied by prodromal symptoms such as fever, sore throat and cough. MIRM mainly manifested as obvious mucosal damage and some targetoid lesions. Most patients could recover after a single attack, and recurrent episodes may be related to mutations in autoinflammation- and infection-related genes in some patients.

Objective To describe the clinical characteristics of idiopathic ventricular fibrillation (IVF) with fragmented QRS complex (f-QRS) and J wave in resting electrocardiogram. Methods We reviewed data from 21 case subjects in our hospital who were resuscitated after cardiac arrest due to IVF and assessed the prevalence of f-QRS and J wave in resting electrocardiogram (ECG). All the case subjects were classified among three groups based on the electrocardiographic morphology: group I, both f-QRS and J wave were observed (n = 6), group II, only J wave was observed (n = 9), group III, neither f-QRS nor J wave was observed (n = 6). Population characteristics, history of syncope or sudden cardiac arrest, incidence of ventricular fibrillation (VF), and circumstance of VF were evaluated among the three groups. Results The incidence of index events (syncope, survived cardiac arrest and VF episodes recorded in implantable cardioverter defibrillator (ICD) or pacemakers) was 13.4 ± 5.6 per-year in group I, 10.8 ± 3.9 per-year in group II, and 9.8 ± 4.2 per-year in group III. There were significant differences in incidences among the three groups, the most frequent index events were observed in group I. The hazard ratio for incidence was 3.2 (95%CI, 1.1-7.9; P = 0.01). The history and circumstance of the index events were different among the groups. In group I, all the index events occurred during sleep in early morning. In group II, four subjects suffered VF during strenuous physical activities or agitation state, two during sleep in early morning, three in usual activity. In group III, one subject suffered VF during sleep in early morning, one in agitation state, four in usual activity. Conclusions This study suggests that the IVF patients with the combined appearance of f-QRS and J wave in the resting ECG suffer an increased risk of VF, this subgroup of IVF patients has a unique clinical feature.

Objective To investigate the expression of Situin 1 ( SIRT1) in 5 strains of human lung adenocarcinoma cell lines, inclu-ding HCC827, H1650, H1975, A549 and H1299, and its relation to the susceptibility of nedaplatin ( NDP ) . Methods The SIRT1 mRNA and protein levels in 5 strains of human lung adenocarcinoma cells were detected by real-time quantitative PCR and Western blot, respectively. The viability of cells treated with NDP was detected by the CCK-8 method and the half growth inhibition concentra-tion ( IC50 ) was calculated. After the expressions of SIRT1 in A549, H1299, H1650 and H1975 cells were down-regulated by the siR-NA interference, the effects of NDP on the viability and apoptosis of these cells were determined by the CCK-8 method and flow cytom-etry, respectively.Results The expression levels of SIRT1 mRNA (4.53 ± 0.74, 3.11 ± 0.64, 15.76 ± 2.28 and 18.09 ± 1.17) and protein (0.23 ± 0.03, 0.21 ± 0.02, 0.52 ± 0.11 and 0.56 ± 0.08) in H1650, H1975, A549 and H1299 cells were significantly higher than that in HCC827 cells (1.00 for SIRT1 mRNA and 0.11 ± 0.02 for SIRT1 protein, F=122.10 and 26.50, respectively, P<0.01). The susceptibility of A549 and H1299 cells to NDP [IC50=(7.38 ± 1.59) and (8.14 ± 1.43) μmol/L, respectively] was significantly higher than that of HCC827, H1650 and H1975 cells [IC50=(26.16±4.35),(22.29±3.26) and (24.41 ± 2.58), respectively, F=30.86, P<0.01].The survivals of A549 and H1299 cells transfected by siSIRT1 and treated with NDP were significantly higher than that in the NC group ( F=235.10 and 39.20, respectively,P<0.01) , and the apoptotic rates were the reverse ( t=7.29 and 6.68, re-spectively, P<0.05) . However, the survivals of H1650 and H1975 cells transfected by siSIRT1 and treated with NDP were significantly lower than that in the NC group ( F=185.40 and 60.09, respectively,P<0.01) , and the apoptotic rates were the reverse ( t=6.15 and 31.36, respectively,P<0.01).Conclusion The expression of SIRT1 in A549 and H1299 cells with high expression of SIRT1 increases their susceptibility to NDP , while that in H1650 and H1975 cells with moderate expression of SIRT1 decreases their susceptibility to NDP, indicating that SIRT1 may play dual roles in the resistance of human lung adenocarcinoma cells to platinum.

Objective:To evaluate the curative effect, safety and feasibility of percutaneous transhepatic cholangio drainage(PTCD) combined with balloon dilatation in treating benign biliary-enteric anastomosis stricture(BBES).Methods:The clinical data of 33 patients with benign biliary-enteric anastomosis stricture, who were admitted to the First Affiliated Hospital of Zhengzhou University during the period from January 2013 to May 2019, were retrospectively analyzed. There were 23 cases of benign etiology and 10 cases of malignant etiology, benign strictures of which 15 cases were located in the hepatic hilum and of which 18 cases outside of it. All patients were considered as benign stenosis by at least two imaging examinations of magnetic resonance imaging of pancreatic or enhanced MRI or enhanced CT, laboratory examinations of tumor markers and other clinical data before operation. 10 cases of malignant etiology were confirmed by intraoperative biopsy and pathology. All patients were treated with balloon dilatation at an interval of 1 to 4 weeks after PTCD. The changes of clinical symptoms, bilirubin and liver function before and after operation were compared and analyzed, and the postoperative complications and anastomotic patency rate were followed up.Results:PTCD combined with balloon dilatation was performed successfully in all patients, and the success rate was 100%. After operation, the benign biliary-enteric anastomosis stricture was significantly improved in all patients, and the clinical symptoms were improved obviously. The liver function and bilirubin decreased significantly in all patients after operation, and there was significant statistical significance ( P<0.05). There is no serious complications such as biliary bleeding and biliary fistula were found after operation. At 3 months, 6 months, 12 months, 24 months and 36 months after operation, the anastomotic patency rates of all patients were 90.9%(30/33), 72.7%(24/33), 63.6%(21/33), 63.6%(21/33), 60.6%(20/33), respectively. During the whole follow-up period, anastomotic restenosis happened in 13 patients, of which 9 cases with restenosis, the benign stenosis site of the anastomosis was the hepatic hilum and of which 4 cases located on the outside of the hepatic hilum. After treatment, the incidence of benign restenosis of the anastomosis at the hepatic hilum (60.0%, 9/15) was higher than that at outside of the hepatic hilum (22.2%, 4/18) and it's statistically significant ( P<0.05). Among the 13 patients with recurrence of BBES, 4 cases underwent choledochojejunostomy for malignant causes and 9 cases with benign causes. The recurrence rates after the first balloon dilatation were 40.0% (4/10) and 39.1% (9/23), respectively, and the average recurrence time was 5.8 months and 6.8 months respectively, the difference was not statistically significant( P>0.05). Conclusion:For the treatment of benign biliary-enteric anastomosis stricture, percutaneous transhepatic cholangio drainage combined with balloon dilatation with reliable curative effect, with high safety and less trauma, with less operative complications, and with repeatability, so it is worth applying in clinic.