Effective annotation of in vivo drug metabolites using liquid chromatography-mass spectrometry (LC-MS) remains a formidable challenge. Herein, a metabolic reaction-based molecular networking (MRMN) strategy is introduced, which enables the "one-pot" discovery of prototype drugs and their metabolites. MRMN constructs networks by matching metabolic reactions and evaluating MS² spectral similarity, incorporating innovations and improvements in feature degradation of MS² spectra, exclusion of endogenous interference, and recognition of redundant nodes. A minimum 75% correlation between structural similarity and MS² similarity of neighboring metabolites was ensured, mitigating false negatives due to spectral feature degradation. At least 79% of nodes, 49% of edges, and 97% of subnetworks were reduced by an exclusion strategy of endogenous ions compared to the Global Natural Products Social Molecular Networking (GNPS) platform. Furthermore, an approach of redundant ions identification was refined, achieving a 10%-40% recognition rate across different samples. The effectiveness of MRMN was validated through a single compound, plant extract, and mixtures of multiple plant extracts. Notably, MRMN is freely accessible online at https://yaolab.network, broadening its applications.

B cell receptor(BCR)is the main molecular basis for B cell specific recognition and binding of antigen,and its complementarity determining region(CDR3)presents high diversity and specificity.Using single-cell immune repertoire sequencing technology can accurately analyze the composition and characteristics of each B cell BCR CDR3 sequence,and can better understand the process and mechanism of B cell differentiation,development,and response.Single-cell immune repertoire sequencing technology provides new ideas and theoretical basis for the pathogenesis,monitoring,diagnosis and treatment of B-cell immune-related diseases.This paper mainly compares and analyzes the commonly used detection methods and detection platforms of B-cell BCR CDR3 receptor library,and focuses on the application,research status and progress of single-cell sequencing technology in B-cell BCR CDR3 recep-tor library.

B cell receptor(BCR)is the main molecular basis for B cell specific recognition and binding of antigen,and its complementarity determining region(CDR3)presents high diversity and specificity.Using single-cell immune repertoire sequencing technology can accurately analyze the composition and characteristics of each B cell BCR CDR3 sequence,and can better understand the process and mechanism of B cell differentiation,development,and response.Single-cell immune repertoire sequencing technology provides new ideas and theoretical basis for the pathogenesis,monitoring,diagnosis and treatment of B-cell immune-related diseases.This paper mainly compares and analyzes the commonly used detection methods and detection platforms of B-cell BCR CDR3 receptor library,and focuses on the application,research status and progress of single-cell sequencing technology in B-cell BCR CDR3 recep-tor library.

Objective To analyze the clinicopathological features of bladder urothelial carcinoma BUC in children and to share the experience of diagnosis and treatment.Methods The clinicopathological data,diagnosis and treatment process of a rare 9-year-old boy with BUC treated in the Second People's Hospital of Kashgar were reported and the literature was reviewed.Results The main clinical symptom is hematuria.Both preoperative urinary ultrasound and CT urography(CTU)identified the tumor,which was then removed with transurethral holmium laser resection under general anesthesia.Postoperative pathology confirmed papillary urothelial neoplasm of low malignant potential(PUNLMP).Epirubicin hydrochloride instillation was administered,and no evidence of recurrence or progress was detected during the 3-month follow-up.Conclusion Bladder urothelial carcinoma in children is extremely rare.The most common symptom is hematuria,and there are no characteristic signs.Urinary ultrasound is the first choice for preoperative imaging,and transurethral resection of the carcinoma results in good recovery.There is no recommendable instillation,and patients need long-term postoperative follow-up.

Six new ent-abietane diterpenoids, abientaphlogatones A-F (1-6), along with two undescribed ent-abietane diterpenoid glucosides, abientaphlogasides A-B (7-8) and four known analogs were isolated from the aerial parts ofPhlogacanthus curviflorus (P. curviflorus). The structures of these compounds were determined using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), one-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) spectra, and quantum chemical calculations. Notably, compounds 5 and 6 represented the first reported instances of ent-norabietane diterpenoids from the genus Phlogacanthus. In the β-hematin formation inhibition assay, compounds 2, 4, 7-10, and 12 displayed antimalarial activity, with IC₅₀ values of 12.97-65.01 μmol·L^-1. Furthermore, compounds 4, 5, 8, and 10 demonstrated neuroprotective activity in PC12 cell injury models induced by H₂O₂ and MPP⁺.
Abietanes/pharmacology* ; Antimalarials ; Hydrogen Peroxide ; Biological Assay ; Plant Components, Aerial

Objective:To explore the sex-based heterogeneity in demographic and pathological trends of lung cancer during the past 30 years.Methods:Patients with primary lung cancer who received surgical treatment in the Department of thoracic surgery, Shanghai Pulmonary Hospital Tongji University from 1989 to 2018 were retrospectively analyzed. The differences between male and female patients in age, smoking history, pathological stage and type were compared. Mann- Kendall trend test was performed for trend analysis. Results:A total of 58 433 patients were included in this study, encompassing 30 729(52.6%) men and 27 , 704(47.4%) women. Compared with male patients, female patients were younger(56.0 years old vs. 59.7 years old), and had a higher proportion of non-smokers(98.3% vs. 52.3%), stage Ⅰ lung cancers(60.6% vs. 49.3%), and adenocarcinoma(93.7% vs. 56.1%, all P-values <0.001). Trend analyses revealed that the proportion of female patients increased year by year, and surpassed males in 2015, with the current ratio of male to female being 1∶1.5. After 2013, the age of onset in females was getting younger, and the average age decreased from 58.7 years old to 54.7 years old( P=0.02). The decrease in the proportion of smoking patients was mainly reflected by male patients(from 68.5% to 31.1%, P<0.01). Stage Ⅰ lung cancers in male and females outnumbered advanced stage in 2012 and 2010, respectively, with a much higher proportion in female patients. Among male patients, adenocarcinoma has replaced squamous cell carcinoma as the most common pathological type since 2012, while in female patients adenocarcinoma remained the most common pathological type of lung cancer, and its proportion continued to increase reaching over 98%. Conclusion:A dramatic change in gender distribution was noticed during the past 30 years. Female patients became the primary population in surgically-treated lung cancers, with a trend of getting younger. The proportion of smokers and squamous cell carcinoma decreased significantly in male patients, and adenocarcinoma has become the most common pathological type of lung cancer. The proportion of stage Ⅰ lung cancers was on a dramatic rise, with the popularization of CT screening for lung cancer.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

OBJECTIVE: To investigate the inhibitory effect of polysaccharide of Atractylodes macrocephala (PAM) on the proliferation and invasion of hepatocellular carcinoma cells and the underlying mechanism. METHODS: Hepatocellular carcinoma HepG2 cells were treated with different concentrations of PAM, and their proliferation and invasive ability were examined using CCK-8 assay and Transwell assay. Immunofluorescence assay was performed to detect the expression level of β-catenin, and real-time PCR and Western blotting were used to detect the mRNA and protein expressions of AKT, GSK-3β and MMP-2 in the cells. The changes in the proliferation, invasiveness and the expressions of pGSK-3β and MMP2 were examined in the cells following treatment with LiCl/PAM/LiCl plus PAM. RESULTS: PAM treatment significantly reduced the cell viability, the number of migration cells, and the expression levels of β-catenin and MMP-2 ( < 0.05), and obviously inhibited the phosphorylation of AKT and GSK-3β in the cells ( < 0.05) in a dose-dependent manner. The rescue experiment showed that LiCl reversed the inhibition of cell proliferation, invasiveness, and the Wnt/β-catenin pathway induced by PAM. CONCLUSIONS PAM can inhibit the proliferation and invasion of hepatocellular carcinoma cells possibly by inhibiting the Wnt/β-catenin signaling pathway.

Objective To explore the formation process of vacuum pressure differential of micro power negative pressure technology to facilitate its clinical application.MethodsThe formation of negative pressure differential and changes of negative pressure values in enclosure space were studied which was formed by liquid aspiration after the compressive polyvinyl alcohol foam material was enclosed.Micro power negative pressure technology was applied to the treatment of the right ear necrosis patient after focal cleaning,and the efficacy was observed.Results Medical adhesive film was raised gradually during the expansion of polyvinyl alcohol foam due to liquid aspiration,and then the enclosure space extended increasingly to form local vacuum negative pressure.The range of maximal negative pressure was between-110 and-200 Pa,and the mean maximal negative pressure value was-132.7 Pa.Micro power negative pressure technology behaved well in healing the wound.Conclusion Micro power negative pressure technology gains advantages in reliability and easy operation over other technologies and products,and may be a new choice for healing of refractory wounds.