The collision cross-sections(CCS)measurement using ion mobility spectrometry(IMS)in combination with mass spectrometry(MS)offers a great opportunity to increase confidence in metabolite identifi-cation.However,owing to the lack of sensitivity and resolution,IMS has an analytical challenge in studying the CCS values of very low-molecular-weight metabolites(VLMs ≤ 250 Da).Here,we describe an analytical method using ultrahigh-performance liquid chromatography(UPLC)coupled to a traveling wave ion mobility-quadrupole-time-of-flight mass spectrometer optimized for the measurement of VLMs in human urine samples.The experimental CCS values,along with mass spectral properties,were reported for the 174 metabolites.The experimental data included the mass-to-charge ratio(m/z),retention time(RT),tandem MS(MS/MS)spectra,and CCS values.Among the studied metabolites,263 traveling wave ion mobility spectrometry(TWIMS)-derived CCS values(TWCCSN2)were reported for the first time,and more than 70％of these were CCS values of VLMs.The TWCCSN2 values were highly repeatable,with inter-day variations of＜1％relative standard deviation(RSD).The developed method revealed excellent TWCCSN2 accuracy with a CCS difference(△CCS)within±2％of the reported drift tube IMS(DTIMS)and TWIMS CCS values.The complexity of the urine matrix did not affect the precision of the method,as evidenced by △CCS within±1.92％.According to the Metabolomics Standards Initiative,55 urinary metabolites were identified with a confidence level of 1.Among these 55 metabolites,53(96％)were VLMs.The larger number of confirmed compounds found in this study was a result of the addition of TWCCSN2 values,which clearly increased metabolite identification confidence.

Background: s/Aims: Atezolizumab/bevacizumab is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC) and may facilitate curative conversion through resection and locoregional therapies. However, there have been very few reports on curative conversion using microwave ablation (MWA). This study aimed to determine the curative conversion rate with MWA using atezolizumab-bevacizumab as the first-line treatment in patients with uHCC, and to compare the characteristics and survival of patients with and without curative conversion. Methods: Consecutive patients with uHCC who were started on atezolizumab-bevacizumab from May 2021 to December 2023 in a single tertiary center were included. Objective response rate (ORR) and disease control rate (DCR) were based on the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria. Results: Twenty consecutive patients with uHCC (60% advanced-stage) were included, 90% exceeding the up-to-7 criteria. The ORR and DCR were 35% and 60%, 35% and 55% using RECIST and mRECIST, respectively. Five patients (25%) underwent successful curative conversion with MWA (four advanced and one intermediate stage) despite a median HCC size of 6.1 cm (range, 2.4-7.3). Two of these patients were tumor and drug-free 132-133 weeks from the 1st atezolizumab-bevacizumab dose. Patients who underwent curative conversion had significantly longer survival than those who did not (P=0.024). Other factors associated with survival were male sex, Child-Pugh class A, and an objective response. Conclusions Despite the relatively large tumor size, successful curative conversion with MWA was achieved with first-line atezolizumab-bevacizumab in uHCC. However, data from prospective multicenter trials are required to determine whether this strategy is universally applicable.

Background: There is a dearth of data on Filipino patients with autoimmune hepatitis (AIH). We aimed to describe the demographic and clinical profiles of patients with AIH and to characterize clinical outcomes and treatment responses. Methods: A retrospective cohort study involving patients from two tertiary centers diagnosed with AIH from January 1, 2007, to December 31, 2019, was included. Disease remission was defined as the normalization of ALT levels, while failure was defined as an increase in ALT levels over baseline or clinical deterioration. Results: A total of 48 patients were identified between 2007 to 2019. The median age at presentation was 51 (27-79 yrs.). Liver cirrhosis was already present in 37.5% (27.1% decompensated) on diagnosis. Aside from a higher histologic activity index in females (p=0.047), there were no gender-specific differences. Disease remission was achieved in 41.9% of patients at 6 months, while only 9.3% failed. At the final disposition, remission rates had slightly increased to 58%, but failure rates had risen to 12%. Treatment responses at both 6 and 12 months and MELD and Child-Pugh class influenced treatment responses at final disposition. Median overall survival was 102 weeks and was influenced by the presence of liver dysfunction and 12 months and final treatment responses. Conclusion Autoimmune hepatitis remains an important cause of morbidity and mortality. The results of the study highlight the need for immunosuppressive therapy to induce early remission for a higher likelihood of subsequent biochemical remission to reduce the risk of liver-related mortality.
Autoimmune Hepatitis ; Liver Cirrhosis ; Steroids ; Azathioprine

Background: Weight loss, though difficult to attain and sustain over time, remains the cornerstone of non-alcoholic fatty liver disease (NAFLD) treatment. We aimed to describe weight changes among NAFLD patients. Methods: This was a retrospective, cohort study of consecutively-identified NAFLD patients with >2 clinic visits from March2007–April2018. Weight changes from baseline were categorized into weight gain, weight loss, and no change. Baseline liver and metabolic biochemistries and non-invasive liver fibrosis tests were correlated with the final weight changes. Succeeding weight changes after the initial follow-up visits were used to determine sustainability of weight loss. Results: Of the 240 patients included, 123 (51.2%), 93 (38.8%), and 24 (10%) had weight gain, weight loss, and no change, respectively. Only 12.5% had >5% weight loss. Duration of follow-up was significantly longer for patients with weight loss (p<0.001). None of the baseline demographic and laboratory data were associated with weight loss. Patients with weight loss also did not have significant changes to their biochemistries and non-invasive liver fibrosis tests compared to patients with weight gain/no change. Compared to patients with weight gain after the initial follow-up, where only 11.8% were able to lose weight on the final visit, 73.1% of patients who lost weight after the initial follow-up were able to sustain their weight loss on the final visit. Conclusions Weight loss is achieved in only a third of NAFLD patients. Although 73% of patients who lost weight initially were able to sustain it, patients who gained weight after the 1st follow-up were unlikely to lose weight on further follow-up.
Non-alcoholic Fatty Liver Disease ; Weight Loss

Traditional Chinese medicine (TCM) was the primary source of medical treatment for the people inhabiting East Asia for thousands of years. These ancient practices have incorporated a wide variety of materia medica including plants, animals and minerals. As modern sciences, including natural products chemistry, emerged, there became increasing efforts to explore the chemistry of this materia medica to find molecules responsible for their traditional use. Insects, including beetles have played an important role in TCM. In our survey of texts and review articles on TCM materia medica, we found 48 species of beetles from 34 genera in 14 different families that are used in TCM. This review covers the chemistry known from the beetles used in TCM, or in cases where a species used in these practices has not been chemically studied, we discuss the chemistry of closely related beetles. We also found several documented uses of beetles in Traditional Korean Medicine (TKM), and included them where appropriate. There are 129 chemical constituents of beetles discussed.