OBJECTIVE To investigate the effect and mechanism of modified Lichong decoction （MLCD） on the apoptosis of transplanted tumor cells in nude mice. METHODS Human gastric cancer AGS cells were cultured， and a nude mice transplanted tumor model was established. The nude mice were divided into the model group and MLCD low-， medium- and high-dose groups （150， 300， 600 mg/kg）. They were given distilled water or the corresponding drug solution by gavage once daily for four consecutive weeks. The size of transplanted tumors in nude mice was measured every six days， and the tumor volume was calculated. After the medication， the nude mice were sacrificed， and the transplanted tumor tissues were isolated. The contents of lactate dehydrogenase （LDH） and reactive oxygen species （ROS） in the transplanted tumor tissues were detected， and the changes in mitochondrial membrane potential were assessed. The pathological morphological changes were observed. The enzymatic activities of caspase-3， caspase-8， and caspase-9， as well as protein expressions of Fas and FasL and mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL in the transplanted tumor tissues， were detected. RESULTS Compared with the model group， the volume of transplanted tumors in nude mice from all MLCD dose groups was reduced to varying degrees. The contents of LDH and ROS， as well as the enzymatic activities of caspase-3， caspase-8 and caspase-9， were significantly increased/enhanced. The mitochondrial membrane potential was significantly decreased. The protein expressions of Fas and FasL， and the mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL were significantly up-regulated. Most of these differences were statistically significant （ P ＜0.05 or P ＜0.01）. Pathological results showed that with increasing doses of MLCD， the cellular density in the transplanted tumor tissues gradually decreased， and typical morphological features of apoptosis， such as loosening and increasing fragmentation， became more prominent. CONCLUSIONS MLCD can induce apoptosis in transplanted tumor cells of nude mice， and its mechanism may be related to the activation of the Fas/FasL pathway and the caspase apoptotic pathway.

Objective:To investigate the causal effects of plasma lipidomics on pancreatitis using Mendelian ran-domization(MR)and evaluate the roles of intra-pancreatic fat deposition(IPFD)and gallstone disease in this relation-ship.Methods:A bidirectional MR analysis was conducted,with 179 plasma lipids as exposures and acute pancreati-tis(AP)and chronic pancreatitis(CP)as outcomes.Data were sourced from genome-wide association studies(GWAS),the UK Biobank,and the FinnGen project.Two-step Mendelian randomization(TSMR)and multivariable Mendelian ran-domization(MVMR)analyses were applied to assess the mediating roles of IPFD and gallstone disease in the associa-tion between plasma lipids and pancreatitis.Results:MR analysis identified two sterols negatively associated with AP(P＜0.05)and seven sterols negatively associated with CP(P＜0.05).One phospholipid showed a positive association with CP(P＜0.05).IPFD was positively associated with both AP and CP.Gallstone disease was confirmed as a risk fac-tor for AP.However,TSMR analysis indicated that neither IPFD nor gallstone disease mediated the relationship be-tween plasma lipids and pancreatitis.Conclusion:The causal relationship exists among plasma lipomics and AP/CP,also between IPFD,cholelithiasis and pancreatitis.These findings highlight novel risk factors and potential biomarkers to support early diagnosis and intervention for pancreatitis.

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Objective:To investigate the causal effects of plasma lipidomics on pancreatitis using Mendelian ran-domization(MR)and evaluate the roles of intra-pancreatic fat deposition(IPFD)and gallstone disease in this relation-ship.Methods:A bidirectional MR analysis was conducted,with 179 plasma lipids as exposures and acute pancreati-tis(AP)and chronic pancreatitis(CP)as outcomes.Data were sourced from genome-wide association studies(GWAS),the UK Biobank,and the FinnGen project.Two-step Mendelian randomization(TSMR)and multivariable Mendelian ran-domization(MVMR)analyses were applied to assess the mediating roles of IPFD and gallstone disease in the associa-tion between plasma lipids and pancreatitis.Results:MR analysis identified two sterols negatively associated with AP(P＜0.05)and seven sterols negatively associated with CP(P＜0.05).One phospholipid showed a positive association with CP(P＜0.05).IPFD was positively associated with both AP and CP.Gallstone disease was confirmed as a risk fac-tor for AP.However,TSMR analysis indicated that neither IPFD nor gallstone disease mediated the relationship be-tween plasma lipids and pancreatitis.Conclusion:The causal relationship exists among plasma lipomics and AP/CP,also between IPFD,cholelithiasis and pancreatitis.These findings highlight novel risk factors and potential biomarkers to support early diagnosis and intervention for pancreatitis.

Cilia,as cellular sensory organelles,actively partici-pate in and regulate cellular processes such as autophagy and metabolic breakdown during their generation and transportation.Autophagy,on the other hand,is a cell self-protection mecha-nism that maintains cellular homeostasis by clearing aggregates and damaged organelles.Combining recent research findings,this review comprehensively elucidates the bidirectional crosstalk between primary cilia and autophagy.Specifically,it highlights the crucial role of cilia-dependent signaling pathways in activa-ting cellular autophagy and how autophagy regulates cilia genera-tion and length by degrading specific ciliary proteins.Moreover,the dysregulation of primary cilia and autophagy is closely asso-ciated with the clinical manifestations and pathogenesis of vari-ous ciliopathy-related diseases such as polycystic kidney disease and tuberous sclerosis.In terms of pharmacotherapy,this review provides a comprehensive and in-depth overview of small mole-cule inhibitors targeting ciliogenesis,including cytoskeletal drugs and Hedgehog signaling pathway inhibitors.Despite the current limitations in clinical use,these drugs lay the groundw-ork for developing highly specific targeted small molecule inhibi-tors of ciliogenesis and for the treatment of ciliopathies and canc-ers.By systematically discussing ciliogenesis,autophagy,disea-ses and drugs,this review offers new insights for further elucida-ting the crosstalk between ciliogenesis and autophagy,exploring their pathological mechanisms in disease development,and de-veloping therapeutic strategies in the future.

Cilia,as cellular sensory organelles,actively partici-pate in and regulate cellular processes such as autophagy and metabolic breakdown during their generation and transportation.Autophagy,on the other hand,is a cell self-protection mecha-nism that maintains cellular homeostasis by clearing aggregates and damaged organelles.Combining recent research findings,this review comprehensively elucidates the bidirectional crosstalk between primary cilia and autophagy.Specifically,it highlights the crucial role of cilia-dependent signaling pathways in activa-ting cellular autophagy and how autophagy regulates cilia genera-tion and length by degrading specific ciliary proteins.Moreover,the dysregulation of primary cilia and autophagy is closely asso-ciated with the clinical manifestations and pathogenesis of vari-ous ciliopathy-related diseases such as polycystic kidney disease and tuberous sclerosis.In terms of pharmacotherapy,this review provides a comprehensive and in-depth overview of small mole-cule inhibitors targeting ciliogenesis,including cytoskeletal drugs and Hedgehog signaling pathway inhibitors.Despite the current limitations in clinical use,these drugs lay the groundw-ork for developing highly specific targeted small molecule inhibi-tors of ciliogenesis and for the treatment of ciliopathies and canc-ers.By systematically discussing ciliogenesis,autophagy,disea-ses and drugs,this review offers new insights for further elucida-ting the crosstalk between ciliogenesis and autophagy,exploring their pathological mechanisms in disease development,and de-veloping therapeutic strategies in the future.

The new generation of artificial intelligence technology,represented by deep learning,has emerged as a crucial driving force in the advancement of new drug research and development.This article creatively proposes a workflow named"Molecular Factory"for the design and optimization of drug molecules based on artificial intelligence technology.This workflow integrates intelligent molecular generation models,high-performance molecular docking algorithms,and accurate protein-ligand binding affinity prediction methods.It has been integrated as a core module into DrugFlow,a one-stop drug design software platform,providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds.Utilizing the"Molecular Factory"module,we conducted the research of second-generation inhibitors against Menin that can combat drug resistance.Through the integration of computational and experimental approaches,we rapidly identified multiple promising compounds.Among them,compound RG-10 exhibited the IC50 values of 9.681 nmol/L,233.2 nmol/L,and 40.09 nmol/L against the wild-type Menin,M327I mutant,and T349M mutant,respectively.Compared to the positive reference molecule SNDX-5613,which has entered Phase Ⅱ clinical trials,RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants.These findings fully demonstrate the unique advantages of the"Molecular Factory"technology in practical drug design and development scenarios.It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures,holding significant value and profound implications for advancing new drug discovery.

The occurrence and development of tumors are closely related to the body's immune function.It has been confirmed that immunotherapy plays a role in the treatment of various cancers.Some traditional Chinese medicines can control the growth and metastasis of tumors by enhancing anti-tumor immunity.Even in the immunosuppressive tumor microenvironment,traditional Chinese medicine can exert anti-tumor effects by upregulating immune responses.Further research on the regulation of the immune mechanisms by traditional Chinese medicine will provide new insights into how traditional Chinese medicine controls tumor growth and metastasis and help improve its effectiveness in the clinical treatment of various cancers.This article aims to provide a theoretical reference for the role of immunoregulation in tumors,summarize its mechanisms in tumors,and traditional Chinese medicine intervention research in tumors for the prevention and treatment of tumors with traditional Chinese medicine.

Objective:To systematically evaluate the relationship between maternal arsenic exposure and neonatal mortality (NM) and infant mortality (IM).Methods:Literature searches were conducted through PubMed, Web of Science, Embase, Cochrane Library, CNKI database, Wanfang Data Knowledge Service Platform, VIP Chinese Journal Service Platform, and the Chinese Biomedical Literature Database to include case-control, cohort, and cross-sectional studies on the relationship between maternal arsenic exposure and NM, IM published domestically and internationally. The search period was from database establishment to June 4, 2023. Data analysis was conducted using Stata MP 16.0 software, and heterogeneity tests were performed using I2 statistics and Q-test. Fixed effect model (no significant heterogeneity, I2≤50%, P≥0.100) or random effect model (significant heterogeneity, I2 > 50%, P < 0.100) was selected according to heterogeneity among study results for meta-analysis. The OR value (95% CI) was used as the effect value, and subgroup analysis was performed based on different exposure index, arsenic exposure levels in drinking water and study types. At the same time, the dose-response relationship between maternal arsenic exposure and NM, IM was analyzed using generalized least square method. Results:Finally, 9 English literature articles (including 3 053 women and 74 172 maternal and infant pairs) were included, including 6 articles on NM outcomes and 8 articles on IM outcomes. After heterogeneity testing, there was significant heterogeneity in NM ( I2 = 75.20%, P = 0.001) and IM ( I2 = 62.50%, P = 0.009) among all studies. Random effect model was used for meta-analysis, and the combined OR values (95% CI) of NM and IM were 1.38 (1.11 - 1.73) and 1.51 (1.21 - 1.89), respectively. According to the exposure index grouping, in the NM outcome, all studies used drinking water arsenic as the exposure index, and the combined OR value (95% CI) of drinking water arsenic was 1.38 (1.11 - 1.73). In the IM outcome, the combined OR values (95% CI) for urinary arsenic and drinking water arsenic were 3.42 (1.38 - 8.47) and 1.44 (1.16 - 1.79), respectively. According to the grouping of arsenic exposure levels in drinking water, the combined OR values (95% CI) for high and low exposure levels ( > 50 and > 10 - 50 μg/L) in NM and IM outcomes were 1.18 (0.97 - 1.44), 1.54 (1.41 - 1.67), and 1.22 (1.03 - 1.43), 1.55 (1.18 - 2.03), respectively. According to the study types grouping, the combined OR values (95% CI) for retrospective, prospective, and cross-sectional studies in NM and IM outcomes were 1.54 (1.41 - 1.67), 1.11 (0.96 - 1.28), 1.90 (1.01 - 3.55), and 1.55 (1.18 - 2.03), 2.01 (0.82 - 4.94), 1.58 (0.87 - 2.88), respectively. The dose-response relationship analysis showed that the dose-response relationship between maternal arsenic exposure and IM exhibited a non-linear trend (χ 2 = 5.75, P = 0.017). Conclusion:Maternal arsenic exposure is correlated with NM and IM, and there is a non-linear dose-response relationship with IM.

Objective:To systematically evaluate the relationship between maternal arsenic exposure and neonatal mortality (NM) and infant mortality (IM).Methods:Literature searches were conducted through PubMed, Web of Science, Embase, Cochrane Library, CNKI database, Wanfang Data Knowledge Service Platform, VIP Chinese Journal Service Platform, and the Chinese Biomedical Literature Database to include case-control, cohort, and cross-sectional studies on the relationship between maternal arsenic exposure and NM, IM published domestically and internationally. The search period was from database establishment to June 4, 2023. Data analysis was conducted using Stata MP 16.0 software, and heterogeneity tests were performed using I2 statistics and Q-test. Fixed effect model (no significant heterogeneity, I2≤50%, P≥0.100) or random effect model (significant heterogeneity, I2 > 50%, P < 0.100) was selected according to heterogeneity among study results for meta-analysis. The OR value (95% CI) was used as the effect value, and subgroup analysis was performed based on different exposure index, arsenic exposure levels in drinking water and study types. At the same time, the dose-response relationship between maternal arsenic exposure and NM, IM was analyzed using generalized least square method. Results:Finally, 9 English literature articles (including 3 053 women and 74 172 maternal and infant pairs) were included, including 6 articles on NM outcomes and 8 articles on IM outcomes. After heterogeneity testing, there was significant heterogeneity in NM ( I2 = 75.20%, P = 0.001) and IM ( I2 = 62.50%, P = 0.009) among all studies. Random effect model was used for meta-analysis, and the combined OR values (95% CI) of NM and IM were 1.38 (1.11 - 1.73) and 1.51 (1.21 - 1.89), respectively. According to the exposure index grouping, in the NM outcome, all studies used drinking water arsenic as the exposure index, and the combined OR value (95% CI) of drinking water arsenic was 1.38 (1.11 - 1.73). In the IM outcome, the combined OR values (95% CI) for urinary arsenic and drinking water arsenic were 3.42 (1.38 - 8.47) and 1.44 (1.16 - 1.79), respectively. According to the grouping of arsenic exposure levels in drinking water, the combined OR values (95% CI) for high and low exposure levels ( > 50 and > 10 - 50 μg/L) in NM and IM outcomes were 1.18 (0.97 - 1.44), 1.54 (1.41 - 1.67), and 1.22 (1.03 - 1.43), 1.55 (1.18 - 2.03), respectively. According to the study types grouping, the combined OR values (95% CI) for retrospective, prospective, and cross-sectional studies in NM and IM outcomes were 1.54 (1.41 - 1.67), 1.11 (0.96 - 1.28), 1.90 (1.01 - 3.55), and 1.55 (1.18 - 2.03), 2.01 (0.82 - 4.94), 1.58 (0.87 - 2.88), respectively. The dose-response relationship analysis showed that the dose-response relationship between maternal arsenic exposure and IM exhibited a non-linear trend (χ 2 = 5.75, P = 0.017). Conclusion:Maternal arsenic exposure is correlated with NM and IM, and there is a non-linear dose-response relationship with IM.