Epigenetic mechanisms play a crucial role in the development and progression of nonalcoholic fatty liver disease （NAFLD）， especially among lean individuals. The research on related epigenetic mechanisms has provided new clues and directions for revealing the underlying causes and treatment strategies of NAFLD. This article introduces the role of epigenetics in the development and progression of NAFLD among lean individuals in recent years， analyzes the latest research advances in the epigenetics of NAFLD in this population， and briefly describes the basic concepts of epigenetics， including DNA methylation， histone modifications， and non-coding RNA regulation. This article also discusses how epigenetic alterations impact the pathogenesis， disease progression， and treatment strategies of NAFLD in lean individuals.

This study reported a 50-year-old female patient who was diagnosed with anti-IgLON family member 5 (anti-IgLON5) antibody-related encephalopathy, presented with cognitive and sleep disorders, autonomic dysfunction and seizures, positive serum IgLON5 antibody but negative cerebrospinal fluid IgLON5 antibody, negative human leukocyte antigen (HLA) by genetic testing, and was diagnosed as anti-IgLON5 antibody-related encephalopathy. After hospital admission, the patient was given intravenous methylprednisolone combined with immunoglobulin immunotherapy, donepezil for improvement of cognition, sodium valproate and oxcarbazepine for prevention and treatment of epileptic seizures, and finally her symptoms improved significantly.

Abnormally activated CDK9 participates in the super-enhancer mediated transcription of short-lived proteins required for cancer cell survival. Targeting CDK9 has shown potent anti-tumor activity in clinical trials among different cancers. However, the study and knowledge on drug resistance to CDK9 inhibitors are very limited. In this study, we established an AML cell line with acquired resistance to a highly selective CDK9 inhibitor BAY1251152. Through genomic sequencing, we identified in the kinase domain of CDK9 a mutation L156F, which is also a coding SNP in the CDK9 gene. By knocking in L156F into cancer cells using CRISPR/Cas9, we found that single CDK9 L156F could drive the resistance to CDK9 inhibitors, not only ATP competitive inhibitor but also PROTAC degrader. Mechanistically, CDK9 L156F disrupts the binding with inhibitors due to steric hindrance, further, the mutation affects the thermal stability and catalytic activity of CDK9 protein. To overcome the drug resistance mediated by the CDK9-L156F mutation, we discovered a compound, IHMT-CDK9-36 which showed potent inhibition activity both for CDK9 WT and L156F mutant. Together, we report a novel resistance mechanism for CDK9 inhibitors and provide a novel chemical scaffold for the future development of CDK9 inhibitors.

Selection and measurement of clinical outcome are key components of clinical research in implant dentistry. Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine took the lead and collaborated with multiple internationally renowned colleges of stomatology to develop an international consensus on the core outcome set and measurement in implant dentistry, which took two years and was published in May, 2023 in Journal of Clinical Periodontology and Clinical Oral Implants Research simultaneously. The consensus, aiming at identifying the full spectrum of benefits and harms of interventions, provides a comprehensive, agreed, and standardized set of outcomes that should be measured and reported as a minimum in clinical trials relating with implant dentistry, bone augmentation, and soft tissue augmentation. The present review describes the methodology and key elements of the consensus to help Chinese clinical researchers fully understand and appropriately apply the core outcome set and improve the overall quality of Chinese clinical research in implant dentistry.

OBJECTIVE：To provide reference for the development and application of pharmacy popular-science video courseware. METHODS ：Combined with the problems existing in the medication of patients with chronic diseases at the present stage and the key points of medication management ，the theme ，content and form of this popular-science were determined ；the video shooting and production were completed ，and publicity and promotion were carried out. Questionnaire survey was conducted ， and the reception of pharmacy outpatient service in our hospital was counted ；the broadcasting effects of popular-science video were analyzed. RESULTS ：The theme of popular-science video courseware was determined to be self-medication management of patients with chronic diseases at home assisted by pharmacists. Combined with the “five moments ”of medication safety proposed by WHO ， the content included six units as knowing pharmacists ，understanding drugs ，taking drugs ，adding drugs ，checking drugs ，and discontinuing drugs. PPT video was used to explain the contents of each unit ，with an average duration of about 25 min. After the first unit was launched ，a total of 39 327 hits were received within two months. A total of 100 questionnaires were sent out ，97 questionnaires were collected （recovery rate of 97.0％）. Among them ，80（82.5％）thought it helpful to watch the video. Within two months after the broadcast of unit 1 video，the reception volume of pharmacy outpatient department of our hospital （1 160 person times ）increased by 104.2％ compared with the two months in the same period last year （568 person times ），and increased by 18.7％ compared with the two months before the broadcast （977 person times ）；99 patients came to the pharmacy outpatient department to consult because of watching the video ，and 55.6％ of the registered patients consulted the demonstration of video courseware and repeatedly mentioned related problems. CONCLUSIONS ：It is a beneficial exploration for pharmacists to develop popular-science video courseware with the theme of safe and rational drug use. It is the direction for future work to increase the scope of disease types ，target different groups of people or focus on different types of drugs and promot them in various forms.

Objective The aim of this study was to investigate the mechanism of sanguinarine(SANG)on the inhibitory pro-liferation in ovarian cancer SKOV3 cells. Methods CCK-8 assay was used to detect proliferation of SKOV3 cells. Flow cytometry was used to detect the effect of SANG on apoptosis in SKOV3 cells. The spectrophotometer was used to detect the production of reac-tive oxygen species(ROS)by SANG. The mouse ovarian cancer xenograft model was used to detect the inhibitory effect of SANG on tumor growth. Results SANG promoted apoptosis in SKOV3 cells in a dose-and time-dependent manner. The SANG-induced ap-optosis was associated with the production of ROS,Activated the c-Jun-N-terminal kinase( JNK) and nuclear factor-κB( NF-κB)signaling pathways. In mouse model of ovarian cancer xenografts,after intravenous injection of mice with SANG,SANG was signifi-cantly inhibited the growth of ovarian cancer xenografts when compared to the control group. SANG also significantly induced apoptosis in ovarian cancer xenografts. Conclusion SANG can significantly inhibit the proliferation of ovarian cancer SKOV3 cells,induce ap-optosis,increase the production of ROS,and inhibit the growth of ovarian cancer.

Objective To demonstrate the clinical characteristics and prognosis of invasive pulmonary aspergillosis (IPA) in respiratory intensive care unit (ICU), for early diagnosis and treatment. Methods The clinical features, treatment and outcome of 17 patients diagnosed as IPA in RICU from May 2015 to April 2018 were analyzed retrospectively. Results The basic diseases of 17 patients were mostly chronic respiratory diseases (14 cases, while 11 cases were chronic obstructive pulmonary disease). One case was proven by IPA criteria, 13 cases were probable and 3 cases were possible. All patients were treated with broad-spectrum antibiotics during hospitalization, and 6 patients were treated with glucocorticoids (oral/intravenous) within 3 weeks of admission and during hospitalization. The main clinical symptoms included cough sputum, dyspnea and fever, among which 4 cases had hemoptysis. Infiltrates were seen in 8 cases, multiple nodules with cavitary lesions in 4 cases, multiple small nodules along the bronchi in 2 cases, and left upper lobe consolidation in the proven case. Sixteen patients were treated with voriconazole alone or in combination with caspofungin. Fourteen patients were tested for voriconazole serum concentration, while 4 were in normal range, 10 were elevated (2 cases were significantly elevated, ＞10 μg/L). Serum concentration of bilirubin did not increase significantly in all paitents after treatment. Serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated in 4 cases with elevated serum concentration of voriconazole and 2 cases with normal serum concentration of voriconazole. Patients with elevated voriconazole concentration did not show significant difference in prognosis compared with those with normal concentration. Eight cases were improved and discharged and 9 gave up and died due to the worsening of the disease. Eight patients received mechanical ventilation (6 cases were invasive and 2 cases were non-invasive), 7 of them eventually gave up treatment and died. Conclusions The clinical features of chronic respiratory diseases with IPA are atypical, however, the patient is critically ill with high mortality. Elevated serum concentration of voriconazole might be more common in severe patients. For those who have a history of systemic application of glucocorticoids, clinical symptoms with hemoptysis, short of breath, radiology with infiltrates, nodular and/or with cavity, and with no response to antibiotics, clinicians should actively seeking evidence of IPA, for early diagnosis, standardized treatment, and improve the prognosis of patients with chronic respiratory diseases complicated with IPA.

Objective To analyze the status and influencing factors of job satisfaction of nurses at public hospitals, providing references for the teambuilding strategy of nurses. Methods Questionnaire survey method was used, in October 2017, to study job satisfaction of 1,047 nurses at 13 public general hospitals, for a countermeasure study. Results Job satisfaction of the nurses was found at a medium level. Specifically, their overall job satisfaction score was 3. 68, and the satisfaction scores of the following dimensions from high to low were: on-the-job training (3. 91), hierarchical nurse use (3. 79), performance appraisal (3. 68), promotion evaluation (3. 67), and remuneration (3. 62) respectively. Contents of the five dimensions are strongly related to the overall job satisfaction (r＞0. 6). Job satisfaction scores of nurses with their differences in positions, annual income, and hospital level were significantly different (P＜ 0. 05). The three main influencing factors for talent turnover rate are remuneration, workplace pressure and work environment. Conclusions Higher remuneration, improved hierarchical management system, and greater attention to nursing care at secondary hospitals are very important for effectively improving the job satisfaction of nurses and ensuring the health care industry.

Objective To investigate the clinical effect of treatment of severe carbon monoxide poisoning with Naoxingjing injection combined with naloxone.Methods Emergency department of affiliated theorem clinical college, hospital 70 patients diagnosed with severe carbon monoxide poisoning from emergency department in June 2014 to December 2016, were randomly divided into observation group and control group 35 cases.In the control group were treated with naloxone treatment, observation group were treated based on the use Naoxingjing injection treatment.The two groups were observed and recorded recovery time, mortality, the incidence of delayed encephalopathy, Glasgow Coma Score(GCS)and serum levels of IL-1β.Results The patients in the observation group total effective rate of 97.14% was significantly higher than 77.14%, and the difference was statistically significant(P<0.05);the recovery time was observed in patients(2.25 ± 0.88)h, significantly shorter than the control group(3.46 ± 1.10)h, and the difference was statistically significant(P<0.05);and follow-up observation group mortality rates were delayed encephalopathy(1.43%, 8.57%)than the control group(17.14%, 25.71%), and the difference was statistically significant(P<0.05);④ observation group were GCS score was (12.77±1.89), significantly better than the control group, and the difference was statistically significant(P<0.05);⑤ observed in patients IL-1β is(65.41±9.93)ng / L was significantly lower than the control group(89.86±10.74)ng / L, and the difference was statistically significant(P<0.05).Conclusion Naoxingjing injection combined with naloxone treatment of severe carbon monoxide poisoning exact clinical effect, can effectively reduce patient recovery time, reduce mortality and morbidity.

Objective To investigate the effects of dopamine combined with norepinephrine on blood lactate and inflammatory factors in elderly patients with severe septic shock. Methods 116 patients with severe septic shock were randomly divided into control group and observation group according to the random number table method , 58 cases in each group. The control group was given the basic treatment of western medicine,the observation group was given Shenfu injection on the basis of the treatment of the control group. The patients were treated for 7 days. The heart rate ( HR) ,mean arterial pressure ( MAP) ,central venous pressure ( CVP) ,blood lactate ( Lac) ,urine output, acute physiology and chronic health score ( APACHEⅡ) were observed before and after treatment. The tumor necrosis factor ( TNF- α) , interleukin -6 ( IL -6 ) and C - reactive protein ( CRP ) were measured before and after treatment. The changes of inflammatory cytokines were observed before and after treatment. The 28-day mortality and average length of hospital stay were observed. Results After treatment,the HR of the control group was not improved compared with before treatment[(121. 32 ± 11. 85)beats/min vs. (123. 65 ± 14. 05)beats/min,t=1. 66,P=0. 98]. The HR of the observation group decreased, and there was significant difference compared with before treatment [(96. 55 ± 10. 65) beats/min vs. (123. 60 ± 13. 98) beats/min,t=11. 84,P=0. 00]. The MAP and CVP of the two groups were higher than before treatment,and there were significant differences compared with before treatment ( all P<0. 05). The urine volume of the two groups was higher than before treatment,and that of the observation group was higher than the control group (t=20. 40,P=0. 00). The score of APACHEⅡ,TNF-α,IL-6 and CRP of the two groups were lower than before treatment,which of the observation group were lower than those of the control group ( all P<0. 05). The difference of 28-day mortality rate between the two groups was not statistically significant(13. 79%vs. 22. 41%,χ2 =1. 45,P=0. 23). The average hospital stay of the observation group was shorter than that in the control group [(23. 39 ± 5. 81)d vs. (28. 76 ± 6. 23)d,t=6. 52,P=0. 00]. Conclusion Dopamine combined with norepinephrine can improve the vital signs of patients with severe septic shock,reduce the concentration of lactate in blood,improve the level of inflammatory factors and heart index.