Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

Drug-induced liver injury influencing factors are complex and have diverse clinical manifestations. Simple and reliable diagnostic methods are still deficient, and further classification of toxicological mechanisms is required. There are numerous pertinent discrepancies between domestic and international guidelines aimed at drug-induced liver injury diagnosis and treatment, with partial to no consensus on the content. The American Gastroenterological Association's 2021 Clinical Guidelines, the Asia-Pacific Association for the Study of the Liver's 2021 Consensus Guidelines, the Council for International Organizations of Medical Sciences' 2020 International Consensus, the European Society's Hepatology Committee's 2019 Clinical Practice Guidelines, and the 2015 Chinese Medical Association Guidelines are five influential clinical guidelines on drug-induced liver injury at home and abroad. The epidemiology, risk factors, diagnosis and evaluation, treatment management, and other contents, particularly traditional Chinese medicine, were compared and analyzed using other relevant consensus opinions or guidelines in order to improve understanding and provide a reference for clinical diagnosis and treatment of drug-induced liver injury.
Humans ; Chemical and Drug Induced Liver Injury/therapy* ; Medicine, Chinese Traditional

Objective To investigate the characteristic manifestation of the peripheral seroimmunological indicators such as cellular immunity and cytokines in drug-induced liver injury (DILI). Methods The medical records of 219 patients with DILI collected in Shuguang Hospital and Baoshan Branch from January 2019 to August 2021 were retrospectively analyzed, grouped according to the type of drug injury and the degree of injury, and their clinical characteristics, biochemical and peripheral serum immunological characteristics were analyzed. analyze.Twenty-nine cases were selected from the healthy subjects as the normal liver function group, and 42 cases of DILI cases who had undergone cytokine and cellular immune evaluation within 1 week before the acute onset treatment were confirmed as the DILI control group. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Fisher test was used to compare the count data between groups. Results Among the 219 DILI patients, 122 (56%) were female and 97 (44 %) were male. 89 cases (40%) of injuries were caused by traditional Chinese medicines, proprietary Chinese medicines or health products, and 130 cases (60%) were caused by western medicines such as anti-tuberculosis and anti-tumor. Among them, 82 cases (37%) were classified as hepatocyte injury type, 17 cases (8%) of cholestatic type, and 120 cases (55%) of mixed injury type. The longest incubation period was 180 days, the shortest was 1 day, and the median was 15 days. Fatigue accounted for 49% of the main symptoms. There were statistically significant differences in cytotoxic T lymphocytes (%) and CD4/CD8 ratio between the traditional Chinese medicine, Chinese patent medicine or health product group and the western medicine group ( Z =2.55 and 3.08, P =0.011 and 0.002, ). From 219 DILI patients, it was confirmed that 42 patients who had detected peripheral immune indicators were compared with 29 patients with normal liver function physical examination. The statistical analysis showed that IL-6 and IL-10 were statistically significant in the peripheral immune serum distribution of DILI. Significance ( Z =3.828 and 2.695, P < 0.001 and 0.007). Conclusion Cytotoxic T lymphocytes may play different roles in the pathogenic mechanisms of Chinese herbal medicines, Chinese patent medicine preparations or health products and western medicines; drugs or drug-protein complexes may affect inflammatory and immune pathways and release related cytokines For example, IL-6 and IL-10 are involved in the pathogenesis of DILI.

Objective To investigate the clinical features of drug-induced liver injury (DILI) due to Tripterygium wilfordii preparation and concomitant medications in patients with rheumatoid arthritis (RA). Methods A retrospective analysis was performed for the clinical data of 112 RA patients with DILI caused by Tripterygium wilfordii preparations and concomitant medications who were treated in Honghu Hospital of Traditional Chinese Medicine from January 2014 to December 2019, and demographic data and the clinical features of DILI were observed to explore the influence of concomitant medications and underlying diseases on DILI. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups and further comparison between two groups. Results All 112 patients had a mean age of 48.13±14.38 years, and there were 81 female patients (72.32%). The most common underlying disease was nonalcoholic fatty liver disease (NAFLD) in 8 patients (7.14%), and as for concomitant medications, 70 patients (62.50%) were treated with Tripterygium wilfordii preparation combined with non-steroid anti-inflammatory drug (NSAID) or disease-modifying anti-rheumatic drug (DMARD). The main clinical manifestation was joint pain in 110 patients (98.21%). Among the 112 patients, 102 (91.07%) had abnormal results of liver biochemical examinations; 66 patients (58.93%) had an RUCAM score of 6-8 points, and 110 patients (98.21%) had mild (grade 1) liver injury. After liver-protecting treatment (for less than 6 months in all patients), all patients had an improvement in liver function without aggravation or death. The Tripterygium wilfordii preparation+glucocorticoid+NSAID/DMARD group with 22 patients had significant increases in the serum levels of alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) compared with the Tripterygium wilfordii preparation+NSAID/DMARD group with 70 patients ( P < 0.05). The 8 patients with NAFLD had a significantly greater increase in serum alanine aminotransferase compared with the 90 patients without underlying diseases ( P < 0.05). Conclusion RA patients may develop DILI due to Tripterygium wilfordii preparation and concomitant medications, which is commonly observed in middle-aged women. Joint pain is the main clinical manifestation, and patients tend to have mild liver injury and good prognosis without marked chronicity. More severe liver injury is observed in patients with combined medication of glucocorticoids and NSAID/DMARD or those with the underlying disease of NAFLD.

OBJECTIVE: To investigate the changes in the functional connectivity (FC) in the right insula between migraine without aura (MWoA) and healthy controls by using resting-state functional magnetic resonance imaging (rs-fMRI), and to observe the instant alteration of FC in MWoA during electroacupuncture (EA) stimulation at Shuaigu (GB8). METHODS: A total of 30 patients with MWoA (PM group) and 30 healthy controls (HC group) underwent rs-fMRI scans. The PM group underwent a second rs-fMRI scan while receiving EA at GB8. The right insula subregions, including the ventral anterior insula (vAI), dorsal anterior insula (dAI) and posterior insula (PI), were selected as the seed points for FC analysis. RESULTS: Aberrant FC, including dAI with right postcentral gyrus, PI with left precuneus, was found among PM before EA (PMa), PM during EA (PMb) and HC. Meanwhile, decreased FC between dAI and the right postcentral gyrus was found in the PMa compared to the HC and PMb. Increased FC between the PI and left precuneus was found in the PMa compared to the HC and PMb. Correlation analysis showed that the FC value of the right postcentral gyrus in PMa was negatively correlated with the scores of Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety. The FC value of the left precuneus in PMa was positively correlated with the visual analogue scale score. CONCLUSION The alteration of FC between the right insula subregions and multiple brain regions may be an important index for MWoA. EA at GB8 was able to adjust the FC between the right insula subregions and parietal lobe, namely, the right dAI and right postcentral gyrus, and the right PI and left precuneus, thereby rendering an instant effect in the management of MWoA.
Brain/diagnostic imaging* ; Electroacupuncture ; Humans ; Magnetic Resonance Imaging/methods* ; Migraine without Aura

Rocuronium bromide is an acetylcholine N2 receptor antagonist, which can be used as an auxiliary drug for general anesthesia. It has been reported that rocuronium has two possible metabolic pathways: N-dealkylation and O-deacetylation, which are mainly taken up by liver and excreted by bile in the form of primary drugs. In this paper, the metabolites of rocuronium in human bile were detected by UHPLC-QE-orbitrap-MS, thirteen metabolites were detected, including eleven phase I metabolites and two phase II metabolites, eleven of which had not been previously reported. At the same time, HEK293 cells overexpressing transporter were used to explore the transmembrane transport mechanism of rocuronium, the results showed that rocuronium was the substrate of MATE1, OCT1, OATP1B1 and OATP1B3. The above research results enrich the metabolic pathway of rocuronium in vivo, and put forward the possible transport mechanism of liver uptake and bile excretion, which can better guide the accurate and safe clinical drug application. The collection of human bile samples in this study was approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Approval Number: 2019-775-130-01).

Background::Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis.Methods::We conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit (ICU) admission in two sites. All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days.Results::From September 27, 2018 to February 12, 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group ( P = 0.032). Cox regression showed that the aminophylline group had a lower hazard of death (hazard ratio = 0.312, 95% confidence interval: 0.129-0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time ( P = 0.039 by the log-rank test). The effects of aminophylline on vasopressor dose, oxygenation index, and sequential organ failure assessment score were time-dependent with treatment. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial. Conclusions::Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis.Trial registration::ChiCTR.org.cn, ChiCTR1800019173.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

ObjectiveTo compare the liver histopathological features of drug-induced liver injury (DILI) caused by Chinese herbal medicine (HM) and that caused by Western medicine (WM), and to investigate the pathological features of HM-DILI. MethodsA total of 50 patients with drug-induced liver injury(DILI) who were diagnosed and treated in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March 2014 to June 2019. All the patients with DILI were enrolled and divided into HM-DILI group and WM-DILI group. A retrospective analysis was performed for the clinical features and the pathological features of the two groups, including the clinical type of DILI, severity of liver injury, and liver histopathological features, especially location and grade of liver inflammation, type and degree of steatosis, and iron deposition. The t test and Mann-Whitney U test was used for comparison of continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; the Mann-Whitney U test was used for comparison of ranked data. ResultsOf all 50 patients, 20 (40.0%) had HM-DILI and 30 (60%) had WM-DILI. There were no significant differences in sex, age, course of disease, and biochemical parameters of liver function between the two groups (all P＞0.05). The main clinical types of the two groups were hepatocellular injury type and the degree of injury which was mainly grade l, and there were no significant differences in the clinical type of DILI and the severity of liver injury between the two groups (both P＞0.05). As for liver histopathological features, both groups had varying degrees of focal necrosis of hepatocytes, steatosis (microvesicular, macrovesicular, and mixed), and fibrous tissue proliferation at the portal area, and compared with the WM-DILI group, the HM-DILI group had significantly greater lymphocyte/plasma cell infiltration in the portal area (χ2=3.860, P＜0.05) and iron deposition in Kupffer cells (χ2=4787, P＜0.05). ConclusionThere are no significant differences in clinical manifestations between HM-DILI and WM-DILI, but patients with HM-DILI have more obvious inflammation in the portal area and iron deposition in Kupffer cells than those with WM-DILI.

Objective To evaluate the clinical efficacy of autologous whole blood injections (AWBI) combined with antihistamines for the treatment of patients with refractory chronic spontaneous urticaria and positive autologous serum skin test (ASST),to evaluate its effect on the expression of the high-affinity IgE receptor (FcεR Ⅰ) and CD63 on basophils,and to analyze the possible mechanism underlying the treatment of ASST-positive chronic urticaria with AWBI.Methods Eighty patients with ASST-positive chronic intractable urticaria were enrolled from Department of Dermatology,The First Hospital Affiliated to Army Medical University between November 2017 and June 2018,and randomly and equally divided into two groups by a random number table:AWBI group and control group were both conventionally treated with oral loratadine and ebastine,and AWBI group were additionally treated with AWBI once a week for 12 sessions.Before the treatment and after 12-week treatment,urticaria activity score of 7 days (UAS7) and dermatology life quality index (DLQI) in the two groups were evaluated.Among 30 patients in the AWBI group,flow cytometry was performed to determine the expression of FcεRⅠ and CD63 on the basophils in the peripheral blood at the baseline,weeks 4,8 and 12 after the initial treatment.Statistical analysis was carried out with GraphPad Prism 7.00 software by t test for the comparison of UAS7 or DLQI scores,Mann-Whitney U test for the comparison of FcεR Ⅰ α expression,paired Wilcoxon signed rank test for comparing FceR Ⅰ α or CD63 expression between two different time points,and Spearman correlation analysis for analyzing the correlation between FcεR Ⅰ α and CD63 expression.Results Before the treatment,no significant differences in UAS7 or DLQI scores were observed between the AWBI group and control group (UAS7:27.15 ± 4.53 vs.26.90 ± 5.22;DLQI:16.88 ± 6.01 vs.17.08 ± 6.79;both P ＞ 0.05).After 12-week treatment,UAS7 and DLQI scores both significantly decreased in the two groups compared with those before the treatment (all P ＜ 0.01),and were significantly lower in the AWBI group than in the control group (UAS7:14.25 ± 7.56 vs.19.93 ± 6.32;DLQI:8.48 ± 4.15 vs.13.93 ± 5.43;both P ＜ 0.01).At the baseline,weeks 4,8 and 12 after the initial treatment,the fluorescence intensities of FcεR Ⅰα on basophils (M [P25,P75]) in the AWBI group were 22 532 (16 740,29 220),16 911 (10 240,21 816),13 282 (7 600,16 848) and 11 466 (7 161,14 578) respectively,and the proportions of CD63+ basophils induced by ASST-positive serum (M [P25,P75]) in the AWBI group were 35.25％ (26.75％,49.13％),25.95％ (19.37％,37.54％),13.57％ (7.79％,19.57％) and 9.87％ (6.43％,16.52％) respectively.At week 4 after the initial treatment,the expression of FcεR Ⅰα and CD63 on basophils in the AWBI group both significantly decreased compared with those at the baseline (both P ＜ 0.01),but significantly increased compared with those at week 8 (both P ＜ 0.01).The changes in FcεR Ⅰ α expression from baseline to week 4,from week 4 to week 8,and from week 8 to week 12 were positively correlated with the changes in CD63 expression induced by ASST-positive serum (r =0.364,0.422,0.455,respectively,all P ＜ 0.05).Conclusion AWBI combined with antihistamines can improve the clinical symptoms of ASST-positive refractory chronic urticaria,likely by affecting the expression of FcεR Ⅰ and CD63 on basophils.