Both type 2 diabetes mellitus (T2DM) and metabolic associated fatty liver disease (MAFLD) fall within the spectrum of metabolic diseases, and they exhibit a bi-directional causal relationship and robust reciprocal association. Their shared pathological cornerstone is insulin resistance (IR), which involves the interplay of mitochondrial dysfunction and chronic inflammation, forming a cascading pathological process of “IR-mitochondrial dysfunction-inflammation”. This largely explains the notable upward trend in T2DM-MAFLD co-occurrence observed over recent years. Exercise intervention, as a safe and effective non-pharmacological approach, can improve the pathological progression of these patients at multiple levels. Following the logical framework of “pathogenesis-efficacy comparison-molecular mechanisms-clinical translation”, this article systematically compares the efficacy and molecular mechanisms of moderate-intensity continuous training (MICT), resistance exercise, high-intensity interval training (HIIT), and combined training. MICT reduces intrahepatic triglycerides by promoting lipolysis and improving cardiorespiratory fitness; resistance exercise increases muscle mass and basal metabolic rate, offering unique advantages in preserving muscle while reducing fat and improving insulin sensitivity; HIIT is a time-efficient exercise modality that enhances patients’ cardiorespiratory fitness and insulin sensitivity by alternating brief periods of vigorous exertion with recovery periods, with a prominent short-term triglyceride-lowering effect; combined training produces synergistic effects, comprehensively improving glucolipid metabolism and showing the best long-term adherence. Mechanistically, exercise exerts its beneficial effects through three common pathways: (1) AMPK-mediated lipid oxidation and mitochondrial biogenesis; (2) IRS/PI3K/Akt-mediated insulin signaling sensitization; and (3) Nrf2/ARE anti-oxidation and TGF-β/Smads anti-fibrosis regulation. Different exercise modalities activate these pathways with distinct emphases: MICT most directly and persistently activates the AMPK pathway; resistance exercise uniquely improves IRS/PI3K/Akt signaling through muscle mass gain; HIIT induces the highest AMPK activation intensity and triggers unique lactate-mediated signaling regulation; combined training integrates the above multiple mechanistic advantages. For clinical translation, multidisciplinary team collaboration is essential to ensure safety and adherence. Individualized prescriptions should be formulated according to the FITT-VP principle and patient phenotypes—frequency of 3-5 sessions/week of aerobic exercise combined with 2-3 sessions/week of resistance exercise; intensity of moderate-intensity (40%-60% heart rate reserve (HRR))aerobic exercise and 60%-80% of one-repetition maximum (1-RM) for resistance exercise; time of at least 150 min/week of moderate-intensity aerobic exercise, 30-60 min per session; type of combined training as the preferred modality; total volume of≥500-1 000 MET-min/week; and progression adjusted every 4-6 weeks—with real-time adjustments supported by wearable devices, ultimately forming a closed-loop management system from initial assessment to long-term follow-up. Notably, current studies have limitations such as small sample sizes and short intervention periods. Future research should focus on long-term follow-up, multi-omics biomarkers, and combined exercise-drug strategies. In conclusion, the systematic integration of structured, individualized, and sustainable exercise interventions into the multidisciplinary management pathway for patients with T2DM complicated by MAFLD is an urgent need in current clinical practice.

Objective To investigate the environmental contamination related to first patient with carbapenem-re-sistant Acinetobacter baumannii(CRAB)infection and the infection status of relevant patients in a newly established intensive care unit(ICU)of a hospital in Tibetan area,and analyze the transmission risk.Methods From the ad-mission in ICU of a patients who was first detected CRAB on November 15,2021 to the 60th day of hospitalization,all patients who stayed in ICU for＞48 hours were performed active screening on CRAB.On the 30th day and 60th day of the admission to the ICU of the first CRAB-infected patient,environment specimens were taken respectively 2 hours after high-frequency diagnostic and therapeutic activities but before disinfection,and after disinfection but before medical activities.CRAB was cultured with chromogenic culture medium.Results Among the 13 patients who were actively screened,1 case was CRAB positive,he was transferred from the ICU of a tertiary hospital to the ICU of this hospital on November 19th.On the 40th day of admission to the ICU,he had fever,increased frequency for sputum suction,and CRAB was detected.The drug sensitivity spectrum was similar to that of the first case,and he also stayed in the adjacent bed of the first case.64 environmental specimens were taken,and 9 were positive for CRAB,with a positive rate of 14.06％,8 sampling points such as the washbasin,door handle and bed rail were positive for CRAB after high-frequency diagnostic and therapeutic activities.After routine disinfection,CRAB was detected from the sink of the washbasin.Conclusion For the prevention and control of CRAB in the basic-level ICU in ethnic areas,it is feasible to conduct risk assessment on admitted patients and adopt bundled prevention and con-trol measures for high-risk patients upon admission.Attention should be paid to the contaminated areas(such as washbasin,door handle,and bed rail)as well as the effectiveness of disinfection of sink of washbasin.

Objective To investigate the clinicopathological characteristics and the factors affecting the prognosis of patients with resectable sarcomatoid carcinoma of the bladder(SCB).Methods A retrospective analysis was conducted with the clinical data of patients with resectable SCB treated at the Second Hospital of Tianjin Medical University between September 2008 and December 2023.The patients were divided into two groups,a bladder-preserving surgery(BPS)group and a radical cystectomy(RC)group,according to the specific surgical approach used for each patient.Kaplan-Meier survival curves were used to evaluate overall survival(OS)in both groups,and Cox regression models were employed to identify risk factors affecting survival.Results A total of 77 patients with resectable SCB were included.Among them,35 patients(45.5％)underwent BPS,while 42 patients(54.5％)underwent RC.Ki-67 expression≥30％was observed in 91.7％of the patients.A total of 92.2％of the patients was tested positive for cytokeratin(CK)and 98.1％for vimentin.In addition,62.5％and 37.5％of patients had the human epidermal growth factor receptor 2(Her-2)scores of 0 and 1+,respectively.The median follow-up time was 23.2 months(ranging from 0.4 to 164.7 months).The 1-year,3-year,and 5-year survival rates for the BPS group and the RC group were as follows,76.2％vs.84.9％,46.7％vs.61.1％,and 35.6％vs.43.2％,respectively.Multivariate Cox regression analysis revealed that in the RC group,age ≥ 75 years old(hazard ratio[HR]=3.836,95％confidence interval[CI]:1.168-12.595,P=0.027),tumor multiplicity(HR=3.439,95％CI:1.235-9.574,P=0.018),and lack of adjuvant therapy(HR=3.164,95％CI:1.015-9.862,P=0.047)were independent risk factors affecting survival.In the BPS group,female sex was identified as an independent risk factor for survival(HR=3.601,95％CI:1.200-10.804,P=0.022).Conclusion Ki-67,CK,and vimentin are significantly overexpressed in SCB patients,while Her-2 is either unexpressed or expressed at low levels.In the RC group,tumor multiplicity,age ≥75 years,and lack of postoperative adjuvant therapy are independent risk factors for overall survival.Female sex is an independent risk factor affecting prognosis in the BPS group.

Objective:To know the clinical characteristics of liver injury related to thalidomide and its analogs.Methods:The relevant databases at home and abroad (up to August 31, 2022) were searched and the case reports on thalidomide and its analogs-associated liver injury were collected. The patients′ gender, age, primary disease, drug use, occurrence of liver injury (onset time, clinical manifestations, liver function status, liver injury classification, etc.), treatment and outcome were recorded and descriptively analyzed.Results:A total of 18 patients were enrolled, including 11 males and 7 females, aged from 36 to 93 years with an average age of 60 years. The primary disease was multiple myeloma in 16 patients, plasma cell leukemia and myelodysplastic syndrome in 1 patient each. Thalidomide was used in 9 patients, lenalidomide in 6 patients and pomalidomide in 3 patients. The time from the beginning of medication to the occurrence of liver injury ranged from 4 to 232 days and it was ≤ 60 days in 15 patients. The classification of liver injury was hepatocellular type in 9 patients, cholestasis type in 7 patients, and unable to be determined due to lack of data in 2 patients. Different degrees of abnormal liver function appeared in 18 patients, mainly including elevated alanine aminotransferase and aspartate aminotransferase (in 16 patients), elevated total bilirubin (in 14 patients), and elevated alkaline phosphatase (in 12 patients). Clinical symptoms were recorded in 15 patients, including jaundice (in 13 cases), fatigue (in 7 cases) and nausea (in 4 cases). After diagnosis of liver injury, thalidomide or its analogues were discontinued in all 18 patients, and 4 cases received symptomatic and supportive therapy. Liver function in 13 patients was improved or returned to normal within 7 to 28 days after drug withdrawal, and 5 patients died (2 cases died of liver failure, 3 cases died of primary diseases or other complications).Conclusions:Thalidomide and its analogs associated liver injury mostly occurs within 2 months after drug administration and the clinical symptoms were similar to those caused by other drugs. After drug withdrawal, the liver function in most patients could be improved or return to normal, but a few may progress to liver failure and death.

Humans ; Whooping Cough/prevention & control* ; Vaccines, Acellular ; China

Objective:To know the clinical characteristics of liver injury related to thalidomide and its analogs.Methods:The relevant databases at home and abroad (up to August 31, 2022) were searched and the case reports on thalidomide and its analogs-associated liver injury were collected. The patients′ gender, age, primary disease, drug use, occurrence of liver injury (onset time, clinical manifestations, liver function status, liver injury classification, etc.), treatment and outcome were recorded and descriptively analyzed.Results:A total of 18 patients were enrolled, including 11 males and 7 females, aged from 36 to 93 years with an average age of 60 years. The primary disease was multiple myeloma in 16 patients, plasma cell leukemia and myelodysplastic syndrome in 1 patient each. Thalidomide was used in 9 patients, lenalidomide in 6 patients and pomalidomide in 3 patients. The time from the beginning of medication to the occurrence of liver injury ranged from 4 to 232 days and it was ≤ 60 days in 15 patients. The classification of liver injury was hepatocellular type in 9 patients, cholestasis type in 7 patients, and unable to be determined due to lack of data in 2 patients. Different degrees of abnormal liver function appeared in 18 patients, mainly including elevated alanine aminotransferase and aspartate aminotransferase (in 16 patients), elevated total bilirubin (in 14 patients), and elevated alkaline phosphatase (in 12 patients). Clinical symptoms were recorded in 15 patients, including jaundice (in 13 cases), fatigue (in 7 cases) and nausea (in 4 cases). After diagnosis of liver injury, thalidomide or its analogues were discontinued in all 18 patients, and 4 cases received symptomatic and supportive therapy. Liver function in 13 patients was improved or returned to normal within 7 to 28 days after drug withdrawal, and 5 patients died (2 cases died of liver failure, 3 cases died of primary diseases or other complications).Conclusions:Thalidomide and its analogs associated liver injury mostly occurs within 2 months after drug administration and the clinical symptoms were similar to those caused by other drugs. After drug withdrawal, the liver function in most patients could be improved or return to normal, but a few may progress to liver failure and death.

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.
Calorimetry, Differential Scanning ; Desiccation ; Drug Compounding/methods* ; Drug Stability ; Silybin ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Technology ; X-Ray Diffraction

Objective:To understand the clinical features of granulomatous hepatitis (GH) induced by intravesical instillation with Bacille Calmette-Guérin vaccine (BCG).Methods:Case reports of GH which was confirmed by liver biopsy and induced by intravesical BCG therapy were collected by searching PubMed and Elsevier databases as of December 2021. The following information of patients including general information, intravesical BCG situations (dose, times of instillation, traumatic catheterization occurrence), GH occurrence (onset time, clinical manifestations, laboratory tests and liver biopsy results), other adverse reactions, treatments, and outcomes were extracted and analyzed descriptively.Results:A total of 23 patients, who were all male, were entered in the analysis, aged from 34 to 80 years with a median age of 66 years. The primary diseases were bladder cancer in 22 patients and ureteral carcinoma in 1 patient. The times of instillation until GH occurred were recorded in 19 patients. Of them, 2 patients had instillation once and the time was 16 at most. Ten patients had traumatic catheterization during the last instillation, including hematuria in 7 patients, pain in 2 patients, and difficulty in urethral intubation in 1 patient. Time from the last instillation to the onset of GH was from 3 h to 440 days (≤7 days in 18 patients, 10, 14, 21, 180, and 440 days in 1 patient respectively) with a median time of 3 days. Among the 23 patients, 21 had fever, 12 had jaundice, 9 had hepatomegaly, 7 had fatigue, 5 had anorexia, 2 had weight loss, and 1 had night sweats; 12 manifested as GH alone and 11 had concomitant adverse reactions. Abnormal liver function appeared in 22 patients, mainly including elevated alkaline phosphatase and elevated aspartate aminotransferase (each in 17 patients). Mycobacterium bovis identification/culture results were recorded in 20 patients and 7 were positive. Liver biopsies showed noncaseating granuloma of epithelioid in 10 patients, noncaseating granuloma in 7 patients, epithelioid granuloma in 4 patients, and hepatic granuloma without details in 2 patients. After discontinuation of BCG instillations and treatments with anti-tuberculosis agents and/or corticosteroids, 22 patients were improved and 1 patient died of BCG sepsis and multiple organ failure.Conclusions:GH usually occurs within 1 week after intravesical instillation with BCG and mainly manifests as fever, jaundice, hepatomegaly, and abnormal liver function, which may be accompanied by other adverse reactions related to BCG instillation. Liver biopsy can help the diagnosis. The prognosis is good after combination therapy with anti-tuberculosis agents and corticosteroids, but death may occur in severe cases.

Objective:To understand the clinical features of granulomatous hepatitis (GH) induced by intravesical instillation with Bacille Calmette-Guérin vaccine (BCG).Methods:Case reports of GH which was confirmed by liver biopsy and induced by intravesical BCG therapy were collected by searching PubMed and Elsevier databases as of December 2021. The following information of patients including general information, intravesical BCG situations (dose, times of instillation, traumatic catheterization occurrence), GH occurrence (onset time, clinical manifestations, laboratory tests and liver biopsy results), other adverse reactions, treatments, and outcomes were extracted and analyzed descriptively.Results:A total of 23 patients, who were all male, were entered in the analysis, aged from 34 to 80 years with a median age of 66 years. The primary diseases were bladder cancer in 22 patients and ureteral carcinoma in 1 patient. The times of instillation until GH occurred were recorded in 19 patients. Of them, 2 patients had instillation once and the time was 16 at most. Ten patients had traumatic catheterization during the last instillation, including hematuria in 7 patients, pain in 2 patients, and difficulty in urethral intubation in 1 patient. Time from the last instillation to the onset of GH was from 3 h to 440 days (≤7 days in 18 patients, 10, 14, 21, 180, and 440 days in 1 patient respectively) with a median time of 3 days. Among the 23 patients, 21 had fever, 12 had jaundice, 9 had hepatomegaly, 7 had fatigue, 5 had anorexia, 2 had weight loss, and 1 had night sweats; 12 manifested as GH alone and 11 had concomitant adverse reactions. Abnormal liver function appeared in 22 patients, mainly including elevated alkaline phosphatase and elevated aspartate aminotransferase (each in 17 patients). Mycobacterium bovis identification/culture results were recorded in 20 patients and 7 were positive. Liver biopsies showed noncaseating granuloma of epithelioid in 10 patients, noncaseating granuloma in 7 patients, epithelioid granuloma in 4 patients, and hepatic granuloma without details in 2 patients. After discontinuation of BCG instillations and treatments with anti-tuberculosis agents and/or corticosteroids, 22 patients were improved and 1 patient died of BCG sepsis and multiple organ failure.Conclusions:GH usually occurs within 1 week after intravesical instillation with BCG and mainly manifests as fever, jaundice, hepatomegaly, and abnormal liver function, which may be accompanied by other adverse reactions related to BCG instillation. Liver biopsy can help the diagnosis. The prognosis is good after combination therapy with anti-tuberculosis agents and corticosteroids, but death may occur in severe cases.

Objective:To investigate the relationship between phase behavior of curcumin （CUR） from self-nanoemulsion drug delivery system （SNEDDS） and stability of the formed nanoemulsion in artificial gastrointestinal fluid. Method:The growth rate of precipitation after dispersion of CUR-SNEDDS was expressed by the change tendency of CUR supersaturation-time curve. The effect of drug loading on crystal nucleation and growth was investigated by ultraviolet-visible spectrometry and polarized light microscope， respectively. X-ray powder diffraction （XRD） and differential scanning calorimetry （DSC） were used to analyze the precipitation forms of CUR-SNEDDS with different drug loading in artificial gastrointestinal fluid. At the same time， the effect of drug loading on the quality stability of nanoemulsion formed by CUR-SNEDDS in artificial gastrointestinal fluid was investigated. Result:In the artificial gastrointestinal fluid， with the increase of drug loading， the area under the supersaturation-time curve of CUR was increased （100% drug loading≈90% drug loading>75% drug loading）， the crystallization nucleation and growth rate were accelerated （100% drug loading>90% drug loading>75% drug loading）， the amorphous proportion in the precipitation composition decreased， the nanoemulsion droplets adhered and distributed unevenly， the particle size and dispersivity were increased. Conclusion:High drug loading promotes the nucleation and growth of crystals， and increases the proportion of crystal forms in the precipitation composition， which leads to the decrease in the stability of the formed nanoemulsion. Therefore， it is suggested that the drug loading of CUR-SNEDDS needs to be controlled below 90%.