ObjectiveUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the metabolites of harmine in rats， in order to explore the differences in distribution of metabolites in rats after single dose（40 mg·kg^-1） intragastric administration of harmine， as well to speculate the metabolic pathways. MethodSD rats were given a single dose of harmine by intragastric administration. Plasma， bile， urine and feces samples were collected after administration， and the samples were processed for determination by UPLC-Q-TOF-MS. The separation was performed on an ACQUITY UPLC™ HSS T3 columu（2.1 mm×100 mm， 1.8 μm） with acetonitrile（A）-0.1% formic acid aqueous solution（B） as mobile phase for gradient elution（0-2 min， 5%A； 2-9 min， 5%-35%A； 9-9.5 min， 35%-100%A； 9.5-12 min， 100%A； 12-12.5 min， 100%-5%A； 12.5-14 min， 5%A）， the mass spectra were obtained in positive ion mode with electrospray ionization（ESI）， the scanning range was m/z 50-1 200. The metabolites of harmine were identified based on the information of the obtained compounds and the literature data， and the metabolic pathways were hypothesized. ResultA total of 42 compounds（harmine and its metabolites） were identified in rats， including 27 in plasma， 17 in bile， 26 in urine and 13 in feces. The metabolic pathways involved in these 42 metabolites included monohydroxylation， dihydroxylation， demethylation， glucuronidation and sulfation. ConclusionHarmine can undergo phase Ⅰ and phase Ⅱ metabolic reactions in rats， and the prototype drug is metabolized rapidly in vivo， and the metabolites are mainly excreted by the kidneys， which can provide a reference basis for the pharmacodynamics and material basis of harmine.

Objective To explore the prescription rules of traditional Chinese medicine (TCM) in the treatment of diabetes periodontitis(DP) and the acting mechanisms of core drug combination. Methods Based on the relevant literature retrieved from the CNKI,Wanfang,VIP and Sinomed,a DP prescription database was established. Excel 2021,SPSS Modeler 18.0 and SPSS Statistics 26.0 were used to conduct the statistics of the frequency,efficacy classifications,properties,flavors,and meridian tropism of the included drugs. Association rule analysis and cluster analysis were performed to screen out the core drug combinations. The active components and action targets of core drug combinations were obtained through TCMSP and HERB. The DP related disease targets were predicted using GeneCards. The Venny platform was used to obtain the intersection of disease targets and drug targets. Key components were screened by Cytoscape to establish an "active component-target" network. Based on STRING platform data,PPI network was constructed by Cytoscape to screen core targets. GO functional annotation and KEGG signaling pathway enrichment analysis were carried out for the intersection targets by DAVID. AutoDockVina was applied for molecular docking between core targets and key components. Results A total of 36 articles were included,and 50 prescriptions involving 100 Chinese herbal medicines were extracted. Alismatis Rhizoma,Rehmanniae Radix Praeparata and Astragali Radix were the most common drugs. The most used drug category was deficiency-nourishing drugs. The properties of the herbs were mainly cold and warm,the major flavors were sweet and bitter,and the main meridian tropisms were kidney and liver. Six categories were classified by clustering analysis. Moutan Cortes-Corni Fructus-Rehmanniae Radix Praeparata was screened out as the core drug combination involving 18 active components,164 drug action targets and 104 intersection of DP targets and drug combination targets. Quercetin,stigmasterol,kaempferol,β-sitosterol,tetrahydroalstonine,and sitosterol were the key components,and AKT1,IL-6,TNF,IL-1B,PTGS2,JUN,TP53,ESR1,and MMP9 were the core targets. GO analysis revealed 3724 biological processes,228 cellular components and 404 molecular functions. KEGG analysis showed that DP was treated by the core drug combination through regulating 235 signaling pathways. Molecular docking results showed that there was a good affinity between the core target and the key component. Conclusion Tonifying deficiency is the main treatment methods of TCM for DP,accompanied by clearing heat and removing dampness,activating blood circulation and removing blood stasis,replenishing qi and nourishing yin. Core drug combination (Moutan Cortes-Corni Fructus-Rehmanniae Radix Praeparata) treats DP through multi-component,multi-target and multi-pathway,which provide a reference for clinical diagnosis and treatment.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Objective:To investigate the epidemiological and clinical characteristics of visceral leishmaniasis (VL) in children, and to analyze the distinguishing features of VL associated hemophagocytic lymphohistiocytosis (HLH), so that to provide reference for the diagnosis and treatment of VL.Methods:Forty-one children with VL admitted to Xi′an Children′s Hospital from July 2012 to June 2021 were enrolled. The clinical data were retrospectively analyzed, including epidemiology, clinical manifestations, laboratory data, diagnostic methods, treatment regimens and outcomes. The patients were divided into VL group and VL+ HLH group according to whether combined with HLH or not, and the clinical characteristics and laboratory findings of the two groups were compared. Two independent samples t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Forty-one children with VL were from different provinces, including Shaanxi Province (70.73%(29/41)), Gansu Province (14.63%(6/41)), Shanxi Province (12.20%(5/41)) and Ningxia Hui Autonomous Region (2.44%(1/41)), and 87.80%(36/41) of them lived in rural areas. The peak age was >1.0 to 3.0 years old (63.41%(26/41)). They were sporadic throughout the year. The main clinical manifestations included fever (97.56%(40/41)), splenomegaly (95.12%(39/41)), lymphadenopathy (82.93%(34/41)) and hepatomegaly (60.98%(25/41)). The numbers of cases that Leishman-Donovan bodies were detected in the first, second and third bone marrow smears were 36, four and one, respectively. Anemia, thrombocytopenia and leukopenia detected by blood routine test were 100.00%(41/41), 78.05%(32/41) and 58.54%(24/41), respectively. There were statistically significant differences in the platelet count, lactate dehydrogenase, alanine aminotransferase, triglycerides, fibrinogen and ferritin between VL group (28 cases) and VL+ HLH group (13 cases) ( t=-2.56, t=2.64, Z=-2.66, t=7.15, t=-5.76 and t=3.86, respectively, all P<0.050). The proportions of hepatomegaly and hemophagocytes found in the bone marrow smears in VL group were both lower than those in VL+ HLH group, and the differences were both statistically significant ( χ2=4.47 and 10.93, respectively, both P<0.050). Twelve cases with VL+ HLH were treated with antimony (for six days) and intravenous immunoglobulin, and the others were treated with antimony only. The cure rates of the patients treated with antimony for one and two courses were 92.68%(38/41) and 4.88%(2/41), respectively. The dose of antimony was increased one third and treatment course was prolonged to eight days in one cured case. After (41.36±31.49) months of follow-up, three cases recurred after five to eight months of cure and all of them were cured after one more course of treatment with antimony. Conclusions:Children with VL are mainly distributed in rural areas. The common clinical manifestations are fever and involvement of reticuloendothelial system, which are not specific. The positive rate of Leishman-Donovan bodies found in bone marrow smears is high, and a few negative cases need repeated bone marrow aspiration. Standardized treatment with antimony for VL in children is effective, and combination therapy with immunoglobulin can be considered if patients with VL associated HLH. Very few cases may recur and antimony is still effective.

Objective:To analyze the distribution characteristics of new pneumoconiosis in different industries in Tianjin from 2009 to 2018, in order to provide a theoretical basis for the prevention and treatment of pneumoconiosis.Methods:In November 2019, the data of new pneumoconiosis cases in Tianjin from 2009 to 2018 were collected and classified according to difference industries. The epidemiological characteristics of new pneumoconiosis in different industries were analyzed based on time, type of pneumoconiosis, type of work, age, and working age.Results:A total of 4657 new cases of pneumoconiosis were reported in Tianjin from 2009 to 2018, 4640 cases (99.63%) in the first stage, 13 cases (0.28%) in the second stage, and 4 case (0.09%) in the third stage. The number of new cases increased with time and then decreased. Among them, there were 3482 males (74.77%) and 1175 females (25.23%) . The proportion of women with new pneumoconiosis in the non-metallic mineral products industry was the highest, and the differences were statistically significant ( P<0.05) . There are differences in the distribution of new pneumoconiosis species in different industries (χ 2=4920.11, P<0.05) . Silicosis is mainly distributed in non-metallic mineral products industry, metal smelting and rolling processing industry, petroleum processing coking and nuclear fuel processing industries. Foundry worker′s pneumoconiosis is mainly distributed in the general equipment manufacturing industry and special equipment manufacturing industry, and cement pneumoconiosis is mainly distributed in the non-metallic mineral products industry. The types of work are mainly distributed in smelting, casting, raw materials and forming workers, and the sum of the three accounts for 36.46% (1689/4657) . The M ( P25, P75) of diagnosis age was 56.0 (50.0, 63.0) years, and the M ( P25, P75) of working age was 19.0 (16.0, 26.0) years. The working age of new pneumoconiosis patients in the petroleum processing, coking and nuclear fuel processing industries is 19.0 (16.0, 26.0) years, which is shorter than that of other industries ( P<0.05) ; The diagnostic age of the general equipment manufacturing industry is 54.0 (49.0, 59.0) years, which is less than that of other industries ( P<0.05) . New pneumoconiosis is mainly distributed in large and medium-sized enterprises. New cases of pneumoconiosis in non-metallic mineral products industry, metal smelting, calendar processing industry and general equipment manufacturing industry are mainly distributed in large and medium-sized enterprises. New cases of pneumoconiosis in the metal products industry, special equipment manufacturing industry and petroleum processing, coking and nuclear fuel processing industries are mainly distributed in large enterprises. Conclusion:The work of preventing and controlling pneumoconiosis in Tianjin has a long way to go. We should implement targeted measures according to the characteristics of pneumoconiosis industry, strengthen the supervision of hazard industries, and effectively control the occurrence of pneumoconiosis.

Objective:To analyze the distribution characteristics of new pneumoconiosis in different industries in Tianjin from 2009 to 2018, in order to provide a theoretical basis for the prevention and treatment of pneumoconiosis.Methods:In November 2019, the data of new pneumoconiosis cases in Tianjin from 2009 to 2018 were collected and classified according to difference industries. The epidemiological characteristics of new pneumoconiosis in different industries were analyzed based on time, type of pneumoconiosis, type of work, age, and working age.Results:A total of 4657 new cases of pneumoconiosis were reported in Tianjin from 2009 to 2018, 4640 cases (99.63%) in the first stage, 13 cases (0.28%) in the second stage, and 4 case (0.09%) in the third stage. The number of new cases increased with time and then decreased. Among them, there were 3482 males (74.77%) and 1175 females (25.23%) . The proportion of women with new pneumoconiosis in the non-metallic mineral products industry was the highest, and the differences were statistically significant ( P<0.05) . There are differences in the distribution of new pneumoconiosis species in different industries (χ 2=4920.11, P<0.05) . Silicosis is mainly distributed in non-metallic mineral products industry, metal smelting and rolling processing industry, petroleum processing coking and nuclear fuel processing industries. Foundry worker′s pneumoconiosis is mainly distributed in the general equipment manufacturing industry and special equipment manufacturing industry, and cement pneumoconiosis is mainly distributed in the non-metallic mineral products industry. The types of work are mainly distributed in smelting, casting, raw materials and forming workers, and the sum of the three accounts for 36.46% (1689/4657) . The M ( P25, P75) of diagnosis age was 56.0 (50.0, 63.0) years, and the M ( P25, P75) of working age was 19.0 (16.0, 26.0) years. The working age of new pneumoconiosis patients in the petroleum processing, coking and nuclear fuel processing industries is 19.0 (16.0, 26.0) years, which is shorter than that of other industries ( P<0.05) ; The diagnostic age of the general equipment manufacturing industry is 54.0 (49.0, 59.0) years, which is less than that of other industries ( P<0.05) . New pneumoconiosis is mainly distributed in large and medium-sized enterprises. New cases of pneumoconiosis in non-metallic mineral products industry, metal smelting, calendar processing industry and general equipment manufacturing industry are mainly distributed in large and medium-sized enterprises. New cases of pneumoconiosis in the metal products industry, special equipment manufacturing industry and petroleum processing, coking and nuclear fuel processing industries are mainly distributed in large enterprises. Conclusion:The work of preventing and controlling pneumoconiosis in Tianjin has a long way to go. We should implement targeted measures according to the characteristics of pneumoconiosis industry, strengthen the supervision of hazard industries, and effectively control the occurrence of pneumoconiosis.

Objective:To explore the association between chest high resolution CT (HRCT) scoring and prognostic factors of interstitial lung disease (ILD) in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM).Methods:The patients with DM admitted to Kailuan General Hospital between January 2017 and December 2019 were included into the study including 13 patients with positiveanti-MDA5 antibody (7 survivors, 6 deaths) and 18 patients with anti-synthase (ARS)-antibody positive. All patients underwent chest HRCT prior to treatment. The consolidation, ground-glass opacity (GGO) and fibrosis were scored to assess HRCT findings. The clinical manifestations were compared between the two groups. Cox regression analysis adjusted for age and sex was used to determine the prognostic factors for anti-MDA5 antibody-related ILD.Results:Compared with ARS patients, glutamyl transferase (GGT) and ferritin levels were significantly higher in MDA5-ILD patients [70.0(37.0, 122.5) vs 21.0(16.5, 33.5), Z=-3.37, P=0.001; 977.0(502.5, 1 366.0) vs 307.1(72.3, 546.9) , Z=-3.44, P=0.001]. The cumulative survival rate was significantly lower in patients with positive anti-MDA5 antibody than in those with positive anti-ARS antibody (100% vs 70%, P=0.001). The DM complicated with acute/subacute interstitial pneumonia (A/SIP) were found to significantly relate to death. There were no significant differences in chest HRCT scoringbetween the survivors and the deceased patients [ HR=1.08, 95% CI(0.95, 1.23), P=0.229; HR=0.97, 95% CI(0.72, 1.30), P=0.814]. Conclusion:Anti-MDA5 antibody is an important index for early diagnosis of DM complicated with acute/subacute interstitial pneumonia (A/SIP). The chest HRCT scoreis is not associated with the prognosis of anti-MDA5 antibody-related ILD patients.

Objective:To analyze the weight score and clinical application of 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) systemic lupus erythematosus (SLE) classification criteria in lupus nephritis patients.Methods:Lupus nephritis patients with renal biopsy results who were admitted in the First Affiliated Hospital of Zhejiang University College of Medicine between January 2014 and December 2018 were enrolled retrospectively. According to whether these patients were treated with glucocorticoids and/or immunosuppressants at the time of renal biopsy, they were divided into untreated group and post-treatment group. The weight scores were compared between the two groups, and the relationship between each weight score and remission after treatment was analyzed. Taking no remission as the end event, Cox regression analysis was used to analyze the influence of each weighted integral on the end event.Results:A total of 153 patients were enrolled, including 131 (85.6%) females. These were 70 (45.8%) patients in the untreated group and 83 (54.2%) patients in the post-treatment group. The patients in the untreated group had higher scores of fever (>38.3℃), blood system involvement, low complement and positive specific antibodies than those in post-treated group (all P<0.05). In a median follow-up of 34 (6-50) months, 99 patients (64.7%) achieved complete remission, 38 patients (24.8%) achieved partial remission and 16 patients (10.5%) had no remission. With no remission as the endpoint event, univariate Cox regression analysis showed that proliferative lupus nephritis (renal score of 10 points vs 8 points) and neuropsychiatric involvement were the risk factors (both P<0.05), while multivariate Cox regression analysis showed that neuropsychiatric involvement ( HR=4.758, 95% CI 1.324-17.101, P=0.017) was an independent risk factor. Conclusion:The weight scores of 2019 EULAR/ACR SLE classification diagnostic criteria have certain predictive value for remission of patients with lupus nephritis.

OBJECTIVE： To establish a method for the determination of harmine derivative DH-330 in rat plasma and to use it for pharmacokinetic behavior evaluation of DH-330 in rats after intragastric administration. METHODS： Using tinidazole as internal standard， after pre-treatment of acetonitrile precipitated protein， UPLC-MS method was adopted to determine the plasma concentration of DH-330. UPLC analysis was performed on Waters ACQUITY BEH C18 column （50 mm×2.1 mm，1.7 μm） with mobile phase consisted of acetonitrile-methanol-0.5％ formic acid aqueous solution（15 ∶ 55 ∶ 30， V/V/V） at flow rate of 0.4 mL/min， while the column temperature was 30 ℃， and sample size was 5 μL. MS analysis was conducted by electrospray ionization source， positive ion scanning， ion source temperature at 124 ℃， DH-330 detection of mass to charge ratio （m/z） of 335.8→334.8， and internal standard m/z of 247.0→81.0. Six Wistar rats were given DH-330 suspension（50 mg/kg） intragastrically. Blood samples were collected from fundus venous plexus capillary before administration （0 h） and 0.25，0.5，1，2，4，6，8，12，24 h after administration. Plasma concentration of DH-330 was determined and plasma concentration-time curves were drawn. Pharmacokinetic parameters were calculated by using Kinetica 5.0 software. RESULTS： The linear ranges of DH-330 were 25.05-2 004 ng/mL（r＝0.999 8），and the limits of quantitation was 25.05 ng/mL. RSDs of intra-day and inter-day were all less than 10％. The accuracy RE was －9.76％ to 4.55％. The extraction recovery was higher than 85％（RSD＜5％）. Stability RE was －2.53％ to 2.29％. They were not affected by matrix effect or residual effect of injection. The pharmacokinetic parameters of DH-330 in rats after intragastric administration included that cmax was （1 162.43±241.72）ng/mL，AUC0-∞ was （3 242.93±652.31）ng·h/mL，t1/2 was （1.93±0.61）h， MRT was （3.23±0.30）h，CL was （16.80±5.30）L/h·kg， Vss was （54.78±19.64）L/kg. CONCLUSIONS： The established method is simple， specific， sensitive， precise and recovery， which can be used for the plasma concentration determination of DH-330 in rats. DH-330 has short half-life， rapid absorption and large apparent distribution volume after intragastric administration in rats， which indicates that it has high lipophilicity and may be mainly distributed in tissues.

OBJECTIVE:To prepare the Albendazole nanoliposomes freeze-dried power and study its properties. METHODS:Freeze-drying method was conducted to prepare Albendazole nanoliposomes freeze-dried power,using the particle size,encapsula-tion efficiency,appearance,redispersibility as indexes,single factor test was combined with orthogonal test to screen freeze-drying preparation technology. The morphological changes,particle size,Zeta potential,moisture content,12 months stability at 4 ℃ be-fore and after freeze-drying were detected. RESULTS:Plus a total content of freeze-dried protective agent was 10%,the ratio of glucose-trehalose-mannitol was 1.0:1.0:3.0,using quick-freeze,pre-freezing 18 h in -35 ℃ refrigerator,dry-freezing 48 h to ob-tain freeze-dried powder. Compared with before freeze-drying,the freeze-dried liposomal morphology had no obvious changes, showing clear phospholipid bilayer membrane structure;the particle sizes before and after freeze-drying were (208.63 ± 1.04) nm and (223.04 ± 2.02) nm,Zeta potentials were (-15.6 ± 0.04) mV and (-19.4 ± 0.06) mV,encapsulation efficiencies were (94.62±0.49)%and(91.10±0.46)%(n=3),respectively. Compared with liposomes,liposomes freeze-dried power had good sta-bility in 12 months at 4 ℃. CONCLUSIONS:Albendazole nanoliposomes freeze-dried power is prepared successfully,its stability is superior to albendazole nanoliposomes,and the freeze-drying technology is feasible.