During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[M+10]+intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[M+10]+has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ioniza-tion.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a').Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.

Irinotecan is an anticancer topoisomerase I inhibitor that acts as a prodrug of the active metabolite, SN-38. Unfortunately, the limited utility of irinotecan is attributed to its pH-dependent stability, short half-life and dose-limiting toxicity. To address this problem, a novel trivalent PEGylated prodrug (PEG-[Irinotecan]₃) has been synthesized and its full-profile pharmacokinetics, antitumor activity and toxicity compared with those of irinotecan. The results show that after intravenous administration to rats, PEG-[Irinotecan]₃ undergoes stepwise loss of irinotecan to form PEG-[Irinotecan]_3‒x (x = 1,2) and PEG-[linker] during which time the released irinotecan undergoes conversion to SN-38. As compared with conventional irinotecan, PEG-[Irinotecan]₃ displays extended release of irinotecan and efficient formation of SN-38 with significantly improved AUC and half-life. In a colorectal cancer-bearing model in nude mice, the tumor concentrations of irinotecan and SN-38 produced by PEG-[Irinotecan]₃ were respectively 86.2 and 2293 times higher at 48 h than produced by irinotecan. In summary, PEG-[Irinotecan]₃ displays superior pharmacokinetic characteristics and antitumor activity with lower toxicity than irinotecan. This supports the view that PEG-[Irinotecan]₃ is a superior anticancer drug to irinotecan and it has entered the phase II trial stage.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq). RESULTS: TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation. CONCLUSION TPCN2 might be a potential protective factor against SLE.
Apoptosis/genetics* ; Cell Division ; Humans ; Jurkat Cells ; Lupus Erythematosus, Systemic/genetics* ; RNA, Small Interfering/genetics*

Objective:To investigate the long-term outcomes of laparoscopic ventral rectopexy (LVR) for obstructive defecation with overt pelvic structural abnormalities.Methods:The retrospective cohort study was conducted. The clinical data of 31 obstructive defecation patients with overt pelvic structural abnormalities who were admitted to the Renji Hospital of Shanghai Jiaotong University School of Medicine from June 2014 to August 2020 were collected. There were 6 males and 25 females, aged 59(range, 32?81)years. All 31 patients underwent LVR through transabdominal approach. Observation indicators: (1) the Cleveland clinic constipation score (CCCS); (2) severity of obstructive defecation; (3) patients assessment of constipation quality of life (PAC-QoL). Follow-up was conducted using telephone interview and outpatient examination up to October 2021. One professional researcher assessed the constipation symptoms and quality of life of patients through outpatient interview or mobile software platform of Questionnaire Star. Measurement data with skewed distribution were represented as M(range), and comparison before and after operation was conducted using the Wilcoxon sign rank test. Results:(1) The CCCS. All 31 patients underwent LVR for the first time and were followed up for 61.8(range, 11.0?87.0)months. The constipation symptoms of the 22 patients were improved. The CCCS of the 31 patients before surgery and at the last follow-up time were 15.8(range, 8.0?26.0) and 10.7(range, 2.0?20.0), respectively, showing a significant difference ( Z=?3.98, P<0.05). (2) Severity of obstructive defecation. The severity scores of frequency of bowel movements, difficult of bowel movements, sensation of incomplete defecation, abdominal distension or pain, time of each bowel movements, daily unsuccessful times of defecation, artificial assisted defecation for the 31 patients were 2.9(range, 1.0?4.0), 3.0(range, 1.0?4.0), 1.9(range, 0?3.0), 0.5(range, 0?3.0), 2.6(range, 2.0?4.0), 2.0(range, 0?4.0), 0.9 (range, 0?2.0) before surgery, versus 1.7(range, 0?4.0), 1.6(range, 0?4.0), 1.2(range, 0?4.0), 0.3(range, 0?3.0), 1.7(range, 0?3.0), 1.4(range, 0?3.0), 0.7(range, 0?2.0) after surgery, respectively. There were significant differences in the frequency of bowel movements, difficult of bowel movements, sensation of in-complete defecation, abdominal distension or pain, time of each bowel movements, daily unsuccessful times of defecation for the 31 patients before and after surgery ( Z=?3.38, ?3.80, ?2.54, ?2.31, ?3.64, ?2.75, P<0.05) and there was no significant difference in the artificial assisted defecation for the 31 patients before and after surgery ( Z=?1.31, P>0.05). (3) PAC-QoL. The score of physical discomfort, satisfaction, worries and concerns, psychological discomfort for the 31 patients were 2.3(range, 1.0?4.0), 3.2(range, 1.0?4.8), 2.2(range, 0.6?4.0), 1.8(range, 0.4?3.9) before surgery, versus 1.6(range, 0?4.0), 2.3(range, 0?4.0), 1.7(range, 0?4.0), 1.3(range, 0?4.0)after surgery, respectively, showing significant differences before and after surgery ( Z=?3.49, ?2.17, ?2.50, ?3.05, P<0.05). Conclusions:The long-term outcomes of LVR for obstructive defecation with overt pelvic structural abnorma-lities are satisfactory. Symptoms as frequency of bowel movements, difficult of bowel movements, sensation of incomplete defecation, abdominal distension or pain, time of each bowel movements and daily unsuccessful times of defecation will be significantly improved after LVR and the constipation quality of life of patients will be improved.

With the rapid development of nanotechnology, the research and development of nanomedicine has become one of the current development directions of drug innovation. The pharmacokinetic characteristics of nanomedicine are significantly different from general drugs because of the scale effect based on nanostructures, and pharmacokinetics studies of nanomedicine may be different from the general drugs. This article focuses on the research strategies and considerations on non-clinical pharmacokinetics of nanomedicine, including test agents, in vivo/in vitro assays, biological sample analysis, data evaluation and analysis etc., providing references for developers.

To investigate the clinical effect of pantoprazole combined with traditional Chinese medicine for gastroesophageal reflux. A total of 50 cases of gastroesophageal reflux selected from January 2019 to December 2019 in Aviation General Hospital were randomly divided into the control group and the observation group. The control group was given pantoprazole, and the observation group was given traditional Chinese medicine combined with pantoprazole. Both groups were treated for 28 days. The recovery of clinical symptoms, status of esophageal mucosa by endoscopy and the incidence of adverse reactions were compared between the two groups. The clinical symptoms and status of esophageal mucosa in both group were obviously improved. Efficiency of the observation group was significantly higher than that of the control group( P<0.05). No serious adverse reactions happened during treatment. Pantoprazole combined with traditional Chinese medicine has definite clinical effects in the treatment of gastroesophageal reflux, which can improve the clinical symptoms and the recovery of esophageal mucosa of patients with high safety.

The development of nano drug delivery systems (NDDSs) provides new approaches to fighting against diseases. The NDDSs are specially designed to serve as carriers for the delivery of active pharmaceutical ingredients (APIs) to their target sites, which would certainly extend the benefit of their unique physi-cochemical characteristics, such as prolonged circulation time, improved targeting and avoiding of drug-resistance. Despite the remarkable progress achieved over the last three decades, the understanding of the relationships between the in vivo pharmacokinetics of NDDSs and their safety profiles is insufficient. Analysis of NDDSs is far more complicated than the monitoring of small molecular drugs in terms of structure, composition and aggregation state, whereby almost all of the conventional techniques are inadequate for accurate profiling their pharmacokinetic behavior in vivo. Herein, the advanced bio-analysis for tracing the in vivo fate of NDDSs is summarized, including liquid chromatography tandem-mass spectrometry (LC-MS/MS), F(o)rster resonance energy transfer (FRET), aggregation-caused quench-ing (ACQ) fluorophore, aggregation-induced emission (AIE) fluorophores, enzyme-linked immunosor-bent assay (ELISA), magnetic resonance imaging (MRI), radiolabeling, fluorescence spectroscopy, laser ablation inductively coupled plasma MS (LA-ICP-MS), and size-exclusion chromatography (SEC). Based on these technologies, a comprehensive survey of monitoring the dynamic changes of NDDSs in struc-ture, composition and existing form in system (i.e. carrier polymers, released and encapsulated drug) with recent progress is provided. We hope that this review will be helpful in appropriate application methodology for investigating the pharmacokinetics and evaluating the efficacy and safety profiles of NDDSs.

Objective: To establish a method for the determination ofsamarium oxide and lanthanum oxide by inductively coupled plasmamass spectrometryin the air of workplace. Methods: Samarium, lanthanum and their compounds in the air of workplace were collected through microporous filter. The samples were digested by nitricacid and perhydrol (V/V=4∶1) and detected by inductively coupled plasmamass spectrometry. Results: The linear range ofsamarium oxide and lanthanum oxide was 0-50.00 μg/L, Sm₂O₃: y=0.0119x, r=0.9999; La₂O₃: y=0.0617x, r=0.9998. The detection limits were less than 0.1 μg/L, and the minimum detection concentration were less than 1.52×10^-5 mg/m³. The sampling efficiency were 100%, the recovery rates were 95.70%-102.01%, and the precision were 0.78%-1.58%. Conclusion The indicators established in this study are conformed with the requirements of Chinese Occupational Standars of GBZ/T 210.4-2008, "The Guidelines for the Development of Occupational Hygiene StandarsMehods Part 4: Determination of Chemical Substances in the Air of Workplace".