OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome. METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded. RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05). CONCLUSION Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).
Humans ; Paroxetine/adverse effects* ; Spleen ; Anxiety ; Syndrome ; Medicine, Chinese Traditional ; Treatment Outcome ; Double-Blind Method

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

OBJECTIVES: To explore the characteristics of postmortem examination, chemical examination and scene investigation of deaths caused by oral diphenidol hydrochloride poisoning, and so as to provide a reference for proper settlement and prevention of such deaths. METHODS: The data of 22 deaths caused by oral diphenidol hydrochloride poisoning in a city from January 2018 to August 2020 were collected, including case details, scene investigations, autopsies, chemical examinations and digital evidence. Thirty-one cases of deaths caused by oral diphenidol hydrochloride poisoning reported in previous literature were also collected. RESULTS: In the 53 oral diphenidol hydrochloride poisoning death cases, 50 cases were suicide, 2 cases were accidental, while 1 case was undetermined. Fifty-two cases were found in the medical records or crime scene investigation reports with doses ranging from 775 mg to 12 500 mg, and 23 deceased were detected with postmortem blood concentrations ranging from 2.71 mg/L to 83.1 mg/L. Clinical symptoms were recorded in 6 patients, including conscious disturbance and convulsion. Among the 45 cases which were performed with external examination, 23 cases autopsied. CONCLUSIONS Most of the deceased of oral diphenidol hydrochloride poisoning were suicide. No significant correlation was found between dose and blood concentration through the retrospective analysis of cases.
Humans ; Retrospective Studies ; Piperidines ; Autopsy ; Suicide ; Poisoning

OBJECTIVE: To observe the effect of Huayu Tongluo (resolving stasis and promoting collateral circulation) moxibustion combined with intradermal needling on depressive symptoms, quality of life and cognitive impairment in patients with mild to moderate depression after cerebral infarction on the basis of western medicine treatment. METHODS: Fifty patients with mild to moderate depression after cerebral infarction were randomly divided into an acupuncture combined with western medication group (group A, 25 cases) and a western medication group (group B, 25 cases). In the group B, paroxetine hydrochloride tablets were taken orally, 20 mg after breakfast, once a day, and the dose could be adjusted to the maximum 40 mg/d according to the patients' condition, for 4 weeks totally. On the basis of the treatment in the group B, the group A was treated with Huayu Tongluo moxibustion, namely aconite cake-separated moxibustion at Baihui (GV 20) and suspended moxibustion at Dazhui (GV 14) and Shenting (GV 24), combined with intradermal needling at Shenmen (HT 7), Jianshi (PC 5), Zusanli (ST 36), etc. Huayu Tongluo moxibustion was performed 6 times a week, and intradermal needling was performed 3 times a week，for 4 weeks totally. In the two groups, the scores of Hamilton depression scale (HAMD), stroke specific quality of life scale (SS-QOL) and mini mental state examination (MMSE) were observed before and after treatment, and the clinical efficacy and safety were compared. RESULTS: After treatment, the HAMD score in the each group was decreased compared with that before treatment (P<0.05), and that in the group A was lower than the group B (P<0.05); after treatment, the SS-QOL score in the group A and MMSE score in the two groups were increased compared with those before treatment (P<0.05), and the SS-QOL score in the group A was higher than the group B (P<0.05). The total effective rate was 88.0% (22/25) in the group A, which was higher than 60.0% (15/25) in the group B (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (4.0% [1/25] vs 16.0%[4/25], P>0.05). CONCLUSION On the basis of the treatment of western medication paroxetine hydrochloride tablets, Huayu Tongluo moxibustion combined with intradermal needling therapy can effectively improve the depressive symptoms, quality of life and cognitive impairment of patients with mild to moderate depression after cerebral infarction.
Humans ; Moxibustion ; Quality of Life ; Paroxetine ; Depression/therapy* ; Cerebral Infarction/therapy*

This study evaluated and compared the efficacy, safety and economy of four Chinese patent medicines(CPMs) in the treatment of functional dyspepsia(FD) using the method of rapid health technology assessment. It aims to provide decision-makers with rapid decision-making information. The eight Chinese and English databases were comprehensively and systematically searched for the relevant clinical research. Studies were screened and evaluated. A total of 110 studies were identified, including 95 randomized controlled trials(RCTs), 7 controlled clinical trials(CCTs), 7 systematic review/Meta-analysis and 1 economic evaluation, among which 28 were Dalitong Granules, 49 were Zhizhu Kuanzhong Capsules, 3 were Biling Weitong Granules and 30 were Qizhi Weitong Granules(Tablets/Capsules). The quality of the included literature was generally low. The efficacy of four CPMs alone or combined with western medicine in the treatment of FD is different. Dalitong Granules was used to treat motility disorder in FD. Zhizhu Kuanzhong Capsules and Qizhi Weitong Granules(Tablets/Capsules) can treat FD patients with anxiety and depression. Qizhi Weitong Granules(Tablets/Capsules) were mainly used in FD for perimenopausal patients. There were no serious adverse reactions in the clinical study of four CPMs in the treatment of FD. Dalitong Granules has better effects than mosapride in the treatment of FD, but the cost is slightly higher. The cost-effectiveness ratio of Zhizhu Kuanzhong Capsules in the treatment of FD patients with anxiety and depression was lower than that of Domperidone. In terms of average daily price, Qizhi Weitong Tablets has the highest price(27.00 yuan per day), Qizhi Weitong Granules has the lowest price(5.04 yuan per day), Biling Weitong Granules has a relatively high price(15.53 yuan per day), followed by Dalitong Granules(13.03 yuan per day). The evidence of Dalitong Granules covered the efficacy, safety and economy, which is relatively complete compared with the other three drugs. It has effective potential in the treatment of motility disorder in FD. Further research in this field in the future is needed.
Capsules ; China ; Chlorobenzenes ; Domperidone/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Dyspepsia/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Stomach ; Sulfides ; Tablets ; Technology Assessment, Biomedical

Since exploding rates of modern mental diseases, application of antidepressants has increased. Worryingly, the antidepressant-induced liver injury has gradually become a serious health burden. Furthermore, since most of the knowledge about antidepressant hepatotoxicity are from pharmacovigilance and clinical case reports and lack of observational studies, the underlying mechanisms are poorly understood and there is a lack of efficient treatment strategies. In this study, antidepressant paroxetine directly triggered inflammasome activation evidenced by caspase-1 activation and downstream effector cytokines interleukin(IL)-1β secretion. The pretreatment of echinatin, a bioactive component of licorice, completely blocked the activation. This study also found that echinatin effectively inhibited the production of inflammasome-independent tumor necrosis factor α(TNF)-α induced by paroxetine. Mechanistically, the accumulation of mitochondrial reactive oxygen species(mtROS) was a key upstream event of paroxetine-induced inflammasome activation, which was dramatically inhibited by echinatin. In the lipopolysaccharide(LPS)-mediated idiosyncratic drug-induced liver injury(IDILI) model, the combination of LPS and paroxetine triggered aberrant activation of the inflammasome to induce idiosyncratic hepatotoxicity, which was reversed by echinatin pretreatment. Notably, this study also found that various bioactive components of licorice had an inhibitory effect on paroxetine-triggered inflammasome activation. Meanwhile, multiple antidepressant-induced aberrant activation of the inflammasome could be completely blocked by echinatin pretreatment. In conclusion, this study provides a novel insight for mechanism of antidepressant-induced liver injury and a new strategy for the treatment of antidepressant-induced hepatotoxicity.
Animals ; Humans ; Mice ; Antidepressive Agents/adverse effects* ; Chemical and Drug Induced Liver Injury, Chronic/prevention & control* ; Glycyrrhiza/chemistry* ; Inflammasomes/drug effects* ; Interleukin-1beta/metabolism* ; Lipopolysaccharides/toxicity* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; Paroxetine/adverse effects* ; Tumor Necrosis Factor-alpha ; Chalcones/therapeutic use*

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) on duodenal mast cells, nerve growth factor (NGF) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), and to explore the mechanism of electroacupuncture at Zusanli (ST 36) on functional dyspepsia (FD). METHODS: Sixty SPF-grade 10-day-old SD rats were randomly divided into a normal group, a model group, a ketotifen group and an EA group, 15 rats in each group. The FD model was prepared by iodoacetamide combined with rat tail clamping method in the model group, the ketotifen group and the EA group. The rats in the ketotifen group were injected intraperitoneally with ketotifen (1 mg•kg^-1•d^-1) for 7 days; the rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), with disperse-dense wave, frequency of 2 Hz/50 Hz and intensity of 0.5 mA, 20 min each time, once a day for 14 days. The gastric emptying rate and small intestinal propulsion rate in each group were observed; the morphology of duodenal mucosa was observed by HE staining; the toluidine blue staining was used to observe the number and degranulation of mast cells in duodenal mucosa; the protein and mRNA expressions of NGF, NTRK1 in duodenum were detected by Western blot and real-time PCR; the level of interleukin-1β (IL-1β) in duodenum was measured by ELISA. RESULTS: Compared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were decreased (P<0.01); compared with the model group, the gastric emptying rate and small intestinal propulsion rate in the ketotifen group and the EA group were increased (P<0.01); the small intestinal propulsion rate in the EA group was higher than that in the ketotifen group (P<0.01). In the model group, local defects in duodenal mucosa were observed with a small amount of inflammatory cell infiltration; no obvious abnormality was found in duodenal mucosa of the other groups. Compared with the normal group, the mast cells of duodenal mucosa in the model group were increased significantly with significant degranulation; compared with the model group, the mast cells of duodenal mucosa in the ketotifen group and the EA group were decreased significantly, and the degranulation was not obvious. Compared with the normal group, the protein and mRNA expressions of NGF, NTRK1 as well as the level of IL-1β in duodenum in the model group were increased (P<0.01); compared with the model group, the protein and mRNA expressions of NGF, NTRK1 as well as the levels of IL-1β in duodenum in the ketotifen group and the EA group were decreased (P<0.01, P<0.05); compared with the ketotifen group, the mRNA expression of NGF, as well as the protein and mRNA expressions of NTRK1 in duodenum in the EA group were decreased (P<0.05, P<0.01). CONCLUSION EA at "Zusanli" (ST 36) could inhibit the activation of duodenal mast cells and regulate the expressions of NGF and its receptor to improve the low-grade inflammatory response of duodenum, resulting in treatment effect on FD.
Acupuncture Points ; Animals ; Duodenum/metabolism* ; Dyspepsia/therapy* ; Electroacupuncture ; Ketotifen ; Mast Cells/metabolism* ; Nerve Growth Factor/metabolism* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Receptor, trkA/genetics*

Zanubrutinib is a highly selective second-generation BTK inhibitor developed in China and first approved by the U.S. Food and Drug Administration (FDA) as a novel antineoplastic drug. In recent years, with the birth of molecularly targeted drugs, the treatment of B-cell lymphoma have entered the era of targeted therapy, and immunotherapy has been widely accepted. Especially in some relapsed and refractory lymphomas, zanubrutinib has shown deep and sustained remissions and a favorable safety, which lays a foundation for precision therapy. In this review the clinical application and new progress for zanubrutinib in B-cell lymphoma was summarized briefly.
Humans ; Lymphoma, B-Cell/drug therapy* ; Piperidines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; Pyrazoles/therapeutic use* ; Pyrimidines/therapeutic use*

The rhizome of giant taro (Alocasia macrorrhiza (L.) Schott), which is a highly adaptable wild plant, is a traditional Chinese herbal medicine. In the current study, the antiproliferative constituents of giant taro were investigated and six new (1-6) and four known piperidine alkaloids (7-10) were isolated from its rhizomes. Their chemical structures and absolute configurations were elucidated using various spectroscopic methods and the Mosher ester method. The isolated alkaloids were screened for the antiproliferative activity through MTT assay. The results indicated that piperidine alkaloids exerted potential antiproliferative activity against HepG2, AGS and MCF-7 tumor cells. Further researches showed that compounds 3-5 dose-dependently decreased the colony formation rate and induced the apoptosis of AGS cells, while compound 4 induced AGS cell death via the proapoptotic pathway. This study demonstrates that the piperidine alkaloids isolated from giant taro exhibit significant antitumor activity, which provides phytochemical evidence for further development and utilization.
Alkaloids/pharmacology* ; Alocasia/chemistry* ; Humans ; Piperidines/pharmacology* ; Plants ; Rhizome/chemistry*

OBJECTIVE: Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI. METHODS: A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function. RESULTS: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. CONCLUSION This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.
Abietanes ; Acute Lung Injury/drug therapy* ; Animals ; Cytokine Release Syndrome ; Cytokines ; Inflammation/drug therapy* ; Lipopolysaccharides/toxicity* ; Macrophage Activation ; Macrophages ; Mice ; Triacetoneamine-N-Oxyl/pharmacology*