1.Association of mixed exposure to lithium, vanadium, uranium, and bismuth in early pregnancy with gestational weight gain
Jiao LI ; Qi LI ; Shuang CHENG ; Jiayi SONG ; Xiaohui GUO ; Xiang WANG ; Di CHENG ; Kefeng FAN ; Ju WANG
Journal of Environmental and Occupational Medicine 2026;43(4):475-484
Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11+0 to 13+6 weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35+0 to 37+6 weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L−1, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g−1 (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.
2.Simultaneous Determination of 21 Kinds of Aconitum Alkaloids in Biological Specimens and Herbal Wines Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry
Ju YANG ; Guo-Jun LI ; Xian-Mou FAN ; Rui-Bin ZHAO ; Shao-Ming SU ; Xu-Xian FU ; En-Jin ZHU ; Qi-Lin HUANG ; Yao QIN ; Li-Na LI
Chinese Journal of Analytical Chemistry 2025;53(8):1391-1401,后插1-后插6,封3
A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.
3.Effect of HER2 on bladder cancer by regulating PI3K-Akt signaling pathway via YWHAE and its mechanism
Long YANG ; Jing CUI ; Fan WANG ; Dan LI ; Qi ZHANG ; Yanlei LI
International Journal of Biomedical Engineering 2025;48(4):365-376
Objective:To investigate the effect of human epidermal growth factor receptor 2 (HER2) on bladder cancer by regulating phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway via tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon peptide (YWHAE) and to examine its mechanism.Methods:The gene expression profiling interactive analysis (GEPIA) database was used to analyze HER2 expression in 408 bladder cancer tissues and 19 adjacent normal tissues. HER2 expression was then compared between 215 tumor protein 53 ( TP53) mutant and 193 TP53 non-mutant bladder cancer tissues. Tissue samples were obtained from patients who underwent surgical resection for bladder cancer in Tianjin Medical University General Hospital between June 2010 and March 2015. Immunohistochemistry and Western blotting were performed to validate HER2 and p53 protein expression, as well as analyze their correlation. Bladder cancer T24 cells were transfected with short hairpin RNA targeting HER2 (shHER2) control (shCon) or shHER2, designated as shCon and shHER2 groups. Bladder cancer UMUC3 cells were transfected with overexpression control (oeCon), HER2 overexpression (oeHER2), oeYWHAE, or short hairpin RNA targeting murine double minute 2 (MDM2) (shMDM2), and were designated as the oeCon, oeHER2, oeYWHAE and shMDM2 groups, respectively. UMUC3 cells were then treated with either 0.1% dimethyl sulfoxide or 100 mmol/L dihydrotestosterone and designated as the solvent control and dihydrotestosterone groups, respectively. Additionally, oeCon and oeYWHAE UMUC3 cells were treated with the PI3K inhibitor LY294002 (25 μmol/L), designated as the LY294002 and LY294002+oeYWHAE groups. On this basis, shHER2 was transfected into the oeCon and oeYWHAE groups, which were then designated as the shHER2-2 and shHER2-2+oeYWHAE groups. The relative expression levels of HER2, YWHAE mRNA, and HER2, p53, YWHAE, MDM2, phosphorylated Akt (p-Akt), and Akt proteins were determined using quantitative reverse transcription PCR and Western blotting. Cell Counting Kit-8, Transwell, and wound-healing assays were performed to evaluate the impact of HER2 on the proliferation, invasion, and migration of bladder cancer cells. Mass spectrometry and co-immunoprecipitation assays were performed to confirm the interaction between YWHAE and HER2, and immunofluorescence was used to detect p53 expression. BALB/c nude mice were subcutaneously injected with 5×10 6 UMUC3 cells in the scapular region. According to the random number table method, they were divided into negative the control group and the transfection group, with 3 mice in each group, and transfected with oeCon and oeHER2, respectively. Tumor volume and weight were measured and calculated, and HER2 and p53 protein expression in bladder cancer tissues was validated by immunohistochemistry and Western blotting. Independent sample t test or Mann-Whitney U test was used to compare the two groups. One-way analysis of variance or Kruskal-Wallis test was used for comparison of multiple groups. Results:GEPIA database analysis demonstrated significantly higher levels of HER2 expression in bladder cancer tissues and in TP53 mutant bladder cancers compared with adjacent normal tissues (both P<0.01). HER2 expression was inversely correlated with p53 expression ( r=?0.6). Immunohistochemistry and Western blotting confirmed that p53 expression level in the bladder cancer tissues (5.32±0.11) was higher than that in the adjacent normal tissues (2.00±0.01), while HER2 expression level in the bladder cancer tissues (1.13±0.02) was lower than that in the adjacent normal tissues (6.20±0.06) (both P<0.01). HER2 mRNA and protein expression, absorbance at 450 nm wavelength ( A450) values, and cell invasion number and cell migration distance in the shHER2 group were all lower than those in the shCon group [0.25±0.01 vs 1.00±0.05, 1.00± 0.01 vs 3.26±0.09, 1.36±0.04 vs 1.65±0.06, (107.00±5.51) vs (202.70±11.61) cells, and (298.70±6.94) vs (454.30±7.84) μm] ( P<0.05, 0.01). HER2 mRNA and protein expression, absorbance ( A450) values, and cell invasion number and cell migration distance in the oeHER2 group were all higher than those in the oeCon group [0.78±0.02 vs 0.46±0.01, 2.05±0.02 vs 1.00±0.00, 1.23±0.06 vs 0.78±0.03, (136.30±5.24) vs (59.00±5.51) cells, and (153.70±7.27) vs (66.33±33.84) μm] ( P<0.05, 0.01). HER2 protein expression level in the dihydrotestosterone group was higher than that in the solvent control (1.83±0.19 vs 1.00±0.00), while p53 protein expression level in the dihydrotestosterone group was lower than that in the solvent control group (1.10±0.10 vs 1.53±0.15) (both P<0.01). The differentially expressed protein between the dihydrotestosterone group and solvent control group was YWHAE. The expression levels of YWHAE mRNA and protein in the dihydrotestosterone group (1.10±0.12 and 3.05±0.03) were higher than those in the solvent control group (0.30±0.12 and 1.00±0.00) (both P<0.01). YWHAE protein expression level in the oeHER2 group was higher than that in the oeCon group (1.37±0.08 vs 1.00±0.00) ( P<0.01) and YWHAE expression level in the bladder cancer tissues was higher than that in the adjacent normal tissues ( P<0.01). YWHAE expression positively correlated with HER2 expression ( r=0.4). Co-immunoprecipitation confirmed direct binding between HER2 and YWHAE. Overexpression of YWHAE significantly reduced p53 expression. The relative expression level of MDM2 protein in the oeYWHAE group (2.73±0.09) was lower than that in the oeCon group (3.43±0.12) ( P<0.01). The relative expression level of MDM2 protein in the shMDM2 group (1.00±0.00) was lower than that in the oeYWHAE group, and the relative expression level of p53 protein (2.00±0.00) was higher than that in the oeYWHAE group (1.07±0.07) (both P<0.01). The relative expression levels of YWHAE and p-Akt protein in the oeYWHAE group (1.23±0.09, 3.00±0.06) were higher than those in the oeCon group (1.00±0.00, 1.13±0.03) ( P<0.05, 0.01). The relative expression level of p-Akt protein in LY294002 group (2.20±0.06) was lower than that in the oeCon group (3.30±0.10), and the relative expression level of p53 protein (2.10±0.06) was higher than that in the oeCon group (1.00±0.00) (both P<0.01). The relative expression level of p-Akt protein in LY294002+oeYWHAE group (2.00±0.06) was lower than that in the oeYWHAE group (3.53±0.14), and the relative expression level of p53 protein (2.10±0.06) was higher than that in the oeYWHAE group (1.00±0.06) (both P<0.01). The relative expression levels levels of YWHAE, p-Akt and MDM2 protein in the shHER2-2 group (1.60±0.15, 1.70±0.06, 0.80±0.06) were lower than those in the oeCon group (2.30±0.06, 2.30±0.06, 1.13±0.09), and the relative expression level of p53 protein (1.83±0.12) was higher than that in the oeCon group (1.00±0.00) ( P<0.05, 0.01). The relative expression level of YWHAE protein in the shHER2-2+oeYWHAE group (2.00±0.06) was lower than that in the oeCon group ( P<0.01), and the relative expression levels of MDM2 and p53 protein (2.63±0.15, 1.13±0.03) were higher than those in the oeCon group ( P<0.05, 0.01). The tumor volume, tumor weight, and relative expression levels of HER2, YWHAE, p-Akt, and MDM2 proteins on day 28 in the transfection group [(5 133.0±185.6) mm 3, (0.65±0.12) g, 2.23±0.02, 4.00±0.12, 3.33±0.06 and 2.24±0.02] were higher than those in the negative control group [(2 633.0±88.2) mm 3, (0.33±0.07) g, 0.98±0.02, 1.27±0.03, 1.29±0.02 and 1.46±0.06] (all P<0.01). The relative expression level of p53 protein (1.21±0.04) was lower than that in the negative control group (3.29±0.04) ( P<0.01). Conclusions:HER2 may promote the malignant progression of bladder cancer by regulating the PI3K-Akt pathway via YWHAE, thereby facilitating MDM2 nuclear translocation and p53 degradation. This ultimately enhances the proliferative, migratory, and invasive capacities of bladder cancer cells.
4.Analysis of reoperation causes in unilateral biportal endoscopy for treating lumbar degenerative diseases
Yuquan LIU ; Guangpeng LI ; Xiang LI ; Bin ZHU ; Weiyang ZUO ; Haining TAN ; Ning LIU ; Qi FEI ; Haibo SUN ; Tianqi FAN ; Yong YANG ; Lingjia YU
International Journal of Surgery 2025;52(2):108-113
Objective:To analyze the reoperation rate and causes during the early adoption phase of unilateral biportal endoscopy (UBE).Methods:The clinical data of 180 patients who underwent UBE performed by a single surgeon at Beijing Friendship Hospital, Capital Medical University from October 2021 to June 2023 were retrospectively analyzed. Clinical and imaging data of patients who underwent reoperation were collected to analyze the causes of reoperation, and the clinical efficacy of the reoperations was also followed up. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used before and after treatment. Results:A total of 180 patients who underwent UBE were included in this study, of which 6 patients underwent reoperation, and the reoperation rate was 3.33%. Among them, 3 cases occurred in the first 90 surgeries and the other 3 occurred in the subsequent 90 surgeries. The causes of reoperation were as follows: recurrent lumbar disc herniation at the same segment postoperatively in 2 cases, insufficient decompression in 2 cases, disc herniation following isolated decompression in 1 case, and immediate postoperative perianal numbness in 1 case. The time between the initial surgery and reoperation ranged from 0 to 187 days, with an average of 63.3 days. The average follow-up time after reoperation was 18.3 months. The visual analogue scale (VAS) and Oswestry disability index (ODI) scores of the patients at the last follow-up were significantly improved compared with those before operation (VAS score of low back pain: 5.2 ± 1.7 before operation, 1.2 ± 0.8 at the last follow-up, P<0.001; VAS score of leg pain: 7.2 ± 1.5 before operation, 1.2 ± 1.2 at the last follow-up, P<0.001; ODI score: 67.3 ± 5.7 before operation, 20.2 ± 8.2 at the last follow-up, P<0.001). The postoperative modified MacNab scores were generally satisfactory (4 cases were rated as excellent, accounting for 66.7%; 2 cases were rated as good, accounting for 33.3%). Except for one patient who experienced dural injury during open revision surgery, there were no serious complications such as nerve damage. Conclusions:In the early stages of UBE surgery, recurrent lumbar disc herniation and inadequate decompression are the primary reasons for reoperation, typically occurring within the first three months postoperatively. Reoperation does not significantly increase the risk of nerve injury. Enhanced early postoperative follow-up is recommended. For symptomatic patients, a second surgery with thorough decompression can yield satisfactory treatment outcomes.
5.Application of perioperative enhanced recovery after surgery clinical pathway for percutaneous vertebro plasty
Xuehu XIE ; Zhiwu ZHANG ; Jisheng LIN ; Hai MENG ; Tianyu BAI ; Zihan FAN ; Nan SU ; Jiashen SHAO ; Jinjun LI ; Guoyu NI ; Feng JIN ; Yong YANG ; Qi FEI
International Journal of Surgery 2025;52(6):415-422
Objective:To evaluate the perioperative application effect of enhanced recovery after surgery (ERAS) clinical pathway in percutaneous vertebro plasty (PVP).Methods:The clinical data of 274 patients who underwent PVP treatment for osteoporotic vertebral compression fracture (OVCF) in Beijing Friendship Hospital, Capital Medical University from May 2023 to August 2024 were retrospectively analyzed. The patients were divided into two groups according to the different numbers of surgical segments: the single-segment group ( n=211) and the multisegment group ( n=63). Patients in the single-segment group underwent single-segment surgery, while patients in the multisegment group underwent surgery on ≥2 segments. The core points of the ERAS clinical pathway adopted in this study include perioperative education, pain management, early mobilization, application of "outfast", and joint guidance from the departments of nutrition and rehabilitation. Comparison was made between the two groups of patients in terms of visual analog scale (VAS) scores for low back pain at preoperative, 2 h, 6 h, 24 h postoperatively, and on the day of discharge; Oswestry disability index (ODI) scores preoperatively and on the day of discharge; time to first ambulation postoperatively, total length of hospital stay, postoperative length of stay, perioperative complications, and perioperative application of Opioid consumption. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as cases and percentage, and the Chi-square test was used for comparison between groups. The VAS pain scores at each stage of the perioperative period were evaluated using repeated measures analysis of variance or generalized estimating equations. Results:Compared with that before the operation [(6.17±0.93) points, (6.29±0.83) points], the VAS scores of low back pain of patients in the single-segment group and the multisegment group at 2 hours after surgery [(3.09±0.82) points, (3.27±0.65) points], 6 hours after surgery [(2.60±0.79) points, (2.62±0.55) points], and 24 hours after surgery [(1.89±0.77) points, (1.97±0.72) points] and on the day of discharge [(1.72±0.71) points, (1.81±0.64) points] were significantly decreased, and the differences were statistically significant ( P<0.05). At the same stage, the VAS scores of low back pain in both groups were not statistically significant ( P>0.05). The ODI scores of patients in the single-segment group and the multisegment group on the day of discharge [(24.21±2.35) points, (24.63±3.31) points] were significantly lower than those before the operation [(64.50±4.81) points, (65.52±4.08) points], and the differences were statistically significant ( P<0.05). There were no statistically significant differences in perioperative complications and the proportion of Opioid drug application between the two groups of patients ( P>0.05). Conclusion:For patients with single-segment or multisegment OVCF, PVP surgical treatment under ERAS clinical pathway management can achieve immediate pain relief, early ambulation exercise, and satisfactory perioperative efficacy.
6.Epidemiological and clinical characteristics of pertussis in Baoshan District, Shanghai, 2017‒2024
Peipei DU ; Yuan NAN ; Qi ZHU ; Xiaojun LI ; Ya GAO ; Yang MENG ; Fan HE ; Lin LI
Shanghai Journal of Preventive Medicine 2025;37(12):976-980
ObjectiveTo analyze the epidemiological and clinical characteristics of pertussis in Baoshan District, Shanghai from 2017 to 2024, so as to provide an evidence-based reference for optimizing prevention and control strategies. MethodsData on pertussis cases were collected from the China Disease Prevention and Control Information System, Shanghai Integrated Management and Immunization Service Information System, and follow-up epidemiological investigations. Descriptive epidemiological analyses were performed to analyze the epidemiological characteristics, clinical manifestations, and vaccine effectiveness. Joinpoint regression analyses were used to examine the temporal trends in incidence rates, and a Poisson model was constructed for spatiotemporal scan analyses. ResultsA total of 1 634 pertussis cases were reported in Baoshan District from 2017 to 2024, with a male-to-female ratio of 1.08∶1. More cases were observed in males than in females, with the age ranged from 20 days to 81 years. Among them, 59.92% were in the 6‒<11 years age group, and 63.34% were students. Low-level sporadic incidence persisted during 2017‒2023, followed by a sharp increase in 2024 (71.37/100 000). Starting in January 2024, the incidence rate showed an upward trend, peaking in May before declining. The majority of cases occurred between April and June. The trend in reported pertussis incidence rates in Baoshan District from 2017 to 2023 showed no statistically significant change (APC=10.039%, t=2.586, P=0.150). Incidence rate rose from January 2024, peaked in May (APC=133.641%, t=3.841, P=0.006), then declined significantly (APC=-47.816%, t=2.586, P<0.001). The 12 subdistricts of Baoshan District were divided into low, medium, and high population density areas, with an average annual reported incidence rate of 6.09/100 000, 8.19/100 000 and 11.96/100 000, respectively. The reported incidence rate increased with an increase in population density. Spatiotemporal scan analyses showed that cases clustered in the southwest and northeast of Baoshan District. Epidemiological follow-up investigations of 1 520 cases revealed that the main clinical symptoms were cough (97.63%) and sputum production (41.58%), and 98.13% of the cases were confirmed by positive nucleic-acid test results. Among the 1 475 cases with immunization records, 83.53% had completed the four-dose pertussis vaccine before onset. The complication incidence rates, from high to low, were in the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group. The duration of cough, from long to short, was observed in the the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group, correspondingly. ConclusionIt is recommended to improve the pertussis surveillance system in medical institutions and establish an active monitoring network, prioritizing deployment in school settings and areas with high population density. Enhancing diphtheria-tetanus-pertussis (DTP) vaccination coverage among 6-year-old children and further optimizing the pertussis immunization strategies are essential to prevent and reduce the risk of pertussis among school-aged children.
7.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
Background:
s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.
Methods:
In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.
Results:
Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.
Conclusions
We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
9.Tanreqing Capsules protect lung and gut of mice infected with influenza virus via "lung-gut axis".
Nai-Fan DUAN ; Yuan-Yuan YU ; Yu-Rong HE ; Feng CHEN ; Lin-Qiong ZHOU ; Ya-Lan LI ; Shi-Qi SUN ; Yan XUE ; Xing ZHANG ; Gui-Hua XU ; Yue-Juan ZHENG ; Wei ZHANG
China Journal of Chinese Materia Medica 2025;50(8):2270-2281
This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified_f_Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Mice
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Lung/metabolism*
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Mice, Inbred C57BL
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Capsules
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Orthomyxoviridae Infections/virology*
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Gastrointestinal Microbiome/drug effects*
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Male
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Humans
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Female
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Influenza A virus/physiology*
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Influenza, Human/virology*
10.Transcriptome analysis and catechin synthesis genes in different organs of Spatholobus suberectus.
Wei-Qi QIN ; Quan LIN ; Ying LIANG ; Fan WEI ; Gui-Li WEI ; Qi GAO ; Shuang-Shuang QIN
China Journal of Chinese Materia Medica 2025;50(12):3297-3306
To study the differences in transcript levels among different organs of Spatholobus suberectus and to explore the genes encoding enzymes related to the catechin biosynthesis pathway, this study utilized the genome and full-length transcriptome data of S. suberectus as references. Transcriptome sequencing and bioinformatics analysis were performed on five different organs of S. suberectus-roots, stems, leaves, flowers, and fruits-using the Illumina NovaSeq 6000 platform. A total of 115.28 Gb of clean data were obtained, with GC content values ranging from 45.19% to 47.54%, Q20 bases at 94.17% and above, and an overall comparison rate with the reference genome around 90%. In comparisons between the stem and root, stem and leaf, stem and flower, and stem and fruit, 10 666, 9 674, 9 320, and 5 896 differentially expressed genes(DEGs) were identified, respectively. The lowest number of DEGs was found in the stem and root comparison group. KEGG enrichment analysis revealed that the DEGs were mainly concentrated in the pathways of phytohormone signaling, phenylalanine biosynthesis, etc. A total of 39 genes were annotated in the catechin biosynthesis pathway, with at least one highly expressed gene found in all organs. Among these, PAL1, PAL2, C4H1, C4H3, 4CL1, 4CL2, and DFR2 showed high expression in the stems, suggesting that they may play important roles in the biosynthesis of flavonoids in S. suberectus. This study aims to provide important information for the in-depth exploration of the regulation of catechin biosynthesis in S. suberectus through transcriptome analysis of its different organs and to provide a reference for the further realization of S. suberectus varietal improvement and molecular breeding.
Catechin/biosynthesis*
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Gene Expression Profiling
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Gene Expression Regulation, Plant
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Plant Proteins/metabolism*
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Fabaceae/metabolism*
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Transcriptome
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Flowers/metabolism*
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Plant Stems/metabolism*
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Plant Leaves/metabolism*
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Plant Roots/metabolism*
;
Fruit/metabolism*

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