BACKGROUND:Human periodontal stem cells have a certain inhibitory effect on the pro-inflammatory function of M1-type macrophages,and it is not clear whether icariin,which has anti-inflammatory and other pharmacological activities,can enhance the inhibitory effect of human periodontal stem cells on M1-type macrophages. OBJECTIVE:To investigate the effect of icariin on M1 macrophages after pretreatment of human periodontal stem cells. METHODS:Primary human periodontal stem cells were isolated,cultured and characterized.THP-1 was induced and M1-type macrophages were identified by immunofluorescence staining and PCR.Human periodontal stem cells were cultured with α-MEM complete medium containing concentrations of 10-7,10-6,10-5,and 10-4 mol/L icariin,and the cytotoxicity of Icariin on human periodontal stem cells was detected by the CCK-8 assay at 1,3,5,and 7 days,respectively.α-MEM complete medium,untreated α-MEM conditioned medium for human periodontal stem cells and α-MEM conditioned medium for human periodontal stem cells pretreated with icariin for 24 hours were conditioned with RPMI-1640 complete medium in a 1:1 ratio for M1-type macrophages in the control,untreated,and pretreated groups,and 24 hours later,the mRNA expression of inflammatory factors in M1 macrophages was detected by RT-PCR.The protein expression of inflammatory factors in M1 macrophages was detected by ELISA.The expression of surface markers and nuclear factor-κB pathway-related proteins in M1/M2 macrophages was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that 10-7,10-6,10-5,10-4 mol/L icariin was not cytotoxic to the human periodontal stem cells,and from day 5 onwards,all the concentrations increased the cell viability,and promoted the cell proliferation.10-4 mol/L icariin was selected for follow-up experiment.(2)RT-PCR and ELISA results showed that compared with the control group,the untreated group and the pretreated group both decreased the expression and secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α of M1-type macrophages(P<0.05),and the pretreated group was lower than the untreated group(P<0.05).(3)Western blot assay results showed that compared with the untreated group,the expression of CD86 was significantly lower in the pretreated group(P<0.05);compared with the control group,the expression of CD206,a surface marker of M2-type macrophages,was elevated in both the untreated and pretreated groups(P<0.01),and it was significantly higher in the pretreated group than in the untreated group(P<0.01).In M1-type macrophages after 24 hours of conditioned culture,compared with the control group,the expression of nuclear factor-κB/P65 was decreased in the untreated group and the pretreated group(P<0.01),and the expression of p-IκBα was decreased only in the pretreated group(P<0.01);the expression of both nuclear factor-κB/P65 and p-IκBα was significantly reduced in the pretreated group compared with the untreated group(P<0.05),while the difference of IκBα in the three groups was not statistically significant.(4)These results indicated that icariin enhanced the inhibitory effect of human periodontal stem cells on M1-type macrophages,and this effect may be related to the inhibition of the nuclear factor-κB signaling pathway of macrophages.

AIM: To observe the influence of different intraocular lens implantation methods on visual quality in patients with cataract.METHODS: Retrospective study. Totally 85 patients(113 eyes)with cataract who received phacoemulsification combined with intraocular lens implantation in the hospital June 2020 to December 2023 were selected. According to the different implanted lenses, they were divided into monofocal group(42 cases, 55 eyes)and bifocal group(43 cases, 58 eyes). The uncorrected near visual acuity(UNVA), uncorrected intermediate visual acuity(UIVA), uncorrected distance visual acuity(UDVA), best corrected near visual acuity(BCNVA), best corrected intermediate visual acuity(BCIVA), best corrected distance visual acuity(BCDVA), contrast sensitivity(CS), objective visual quality, National Eye Institute 25-item Visual Function Questionnaire(NEI-VFQ-25)scores and complications were compared between both groups of patients at 3 mo after surgery.RESULTS:At 3 mo after surgery, the UNVA(LogMAR)of the bifocal group was significantly better than that of the monofocal group(0.24±0.06 vs 0.53±0.13, P<0.001), but there were no statistical differences in UIVA, UDVA, BCNVA, BCIVA and BCDVA between the two groups(all P>0.05). The 18 c/d spatial frequency scotopic CS in the bifocal group at 3 mo after surgery was significantly lower than that in the monofocal group(0.84±0.17 vs 0.92±0.22, P<0.05), while the CS in other frequency was not statistically significant(all P>0.05); the objective scatter index(OSI)was higher in the bifocal group than that in the monofocal group(P<0.05), while OV 20% and OV 9% were lower than those in monofocal group(all P<0.05), but there were no statistically significant differences in modulation transfer function cut off(MTFcut off), Strehl ratio(SR)and OV 100% between the two groups(all P>0.05). The scores of overall visual acuity and near visual activity in the bifocal group at 3 mo after surgery were higher than those in the monofocal group(all P<0.001), but there were no statistical differences in the scores of dimensions of overall health, distance visual activity, peripheral visual acuity, color vision, dependence degree, social function, social role and mental health between the two groups(all P>0.05). Furthermore, there were no statistical significance in the incidence of complications in the two groups(P>0.05).CONCLUSION: Phacoemulsification combined with bifocal intraocular lens implantation can provide more ideal near visual acuity and visual-related quality of life for patients with cataract, but its objective visual quality is worse, The two types of intraocular lenses have their own advantages and disadvantages, and it is still necessary to choose the appropriate intraocular lens according to the actual needs of patients.

AIM: To observe the influence of different intraocular lens implantation methods on visual quality in patients with cataract.METHODS: Retrospective study. Totally 85 patients(113 eyes)with cataract who received phacoemulsification combined with intraocular lens implantation in the hospital June 2020 to December 2023 were selected. According to the different implanted lenses, they were divided into monofocal group(42 cases, 55 eyes)and bifocal group(43 cases, 58 eyes). The uncorrected near visual acuity(UNVA), uncorrected intermediate visual acuity(UIVA), uncorrected distance visual acuity(UDVA), best corrected near visual acuity(BCNVA), best corrected intermediate visual acuity(BCIVA), best corrected distance visual acuity(BCDVA), contrast sensitivity(CS), objective visual quality, National Eye Institute 25-item Visual Function Questionnaire(NEI-VFQ-25)scores and complications were compared between both groups of patients at 3 mo after surgery.RESULTS:At 3 mo after surgery, the UNVA(LogMAR)of the bifocal group was significantly better than that of the monofocal group(0.24±0.06 vs 0.53±0.13, P<0.001), but there were no statistical differences in UIVA, UDVA, BCNVA, BCIVA and BCDVA between the two groups(all P>0.05). The 18 c/d spatial frequency scotopic CS in the bifocal group at 3 mo after surgery was significantly lower than that in the monofocal group(0.84±0.17 vs 0.92±0.22, P<0.05), while the CS in other frequency was not statistically significant(all P>0.05); the objective scatter index(OSI)was higher in the bifocal group than that in the monofocal group(P<0.05), while OV 20% and OV 9% were lower than those in monofocal group(all P<0.05), but there were no statistically significant differences in modulation transfer function cut off(MTFcut off), Strehl ratio(SR)and OV 100% between the two groups(all P>0.05). The scores of overall visual acuity and near visual activity in the bifocal group at 3 mo after surgery were higher than those in the monofocal group(all P<0.001), but there were no statistical differences in the scores of dimensions of overall health, distance visual activity, peripheral visual acuity, color vision, dependence degree, social function, social role and mental health between the two groups(all P>0.05). Furthermore, there were no statistical significance in the incidence of complications in the two groups(P>0.05).CONCLUSION: Phacoemulsification combined with bifocal intraocular lens implantation can provide more ideal near visual acuity and visual-related quality of life for patients with cataract, but its objective visual quality is worse, The two types of intraocular lenses have their own advantages and disadvantages, and it is still necessary to choose the appropriate intraocular lens according to the actual needs of patients.

Objective To explore the diagnostic value of mediastinal lymph nodes CT image features in pulmonary sarcoidosis.Methods The imageologic data of the patients with pulmonary sarcoidosis(pulmonary sarcoidosis group)and lung cancer complicating mediastinal lymph node metastasis(lung cancer group)con-firmed by EBUS-TBNA in this hospital from June 2015 to November 2023 were analyzed retrospectively.The chest plain scan CT and enhanced scan CT were performed in all cases,and the imaging characteristics were compared between the two groups.The receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was calculated.The diagnostic value of CT imaging characteristics in pulmonary sar-coidosis was analyzed.Results The proportion of female patients in the lung sarcoidosis group was signifi-cantly higher than that in the lung cancer group,while the age was smaller than that in the lung cancer group,and the differences were statistically significant(P＜0.05).The number of mediastinal lymph nodes,location,short diameter and CT enhancement value in the pulmonary sarcoidosis group had statistical difference(P＜0.05).The ROC curve analysis showed that AUC of lymph node short diameter reciprocal,CT enhancement value and position in detection alone were 0.586,0.785 and 0.505 respectively,and AUC of the three combined reciprocal was the highest(0.789).Conclusion The lymph node short diameter,CT enhancement value and po-sition have certain value in clinical diagnosis of pulmonary sarcoidosis and the 3-indicator combination could increase the diagnostic efficiency of pulmonary sarcoidosis.

OBJECTIVE To investigate the therapeutic mechanisms of electroacupuncture at"Tianshu"(ST25)and"Sanyinjiao"(SP6)acupoints combined with metformin in the treatment of type 2 diabetes mellitus(T2DM)using serum non-targeted metabolomics.METHODS Male SD rats were randomly divided into blank group,model group,metformin group,electroacupunc-ture group,and acupuncture-medicine combination(electroacupuncture combined with metformin)group.A type 2 diabetes model was established by high-fat diet combined with intraperitoneal injection of streptozotocin.The metformin group was treated with 250 mg·kg-1 metformin by gavage,the electroacupuncture group was treated with bilateral Tianshu and Sanyinjiao,the acupuncture-medicine combination group was treated with metformin by gavage combined with electroacupuncture,and the blank group and model group were treated with normal saline by gavage.All rats were treated 6 times a week for 7 weeks.After the intervention,the blood glucose level in the tail vein of the rats was measured using a blood glucose meter in the fasting state.The blood glucose levels of the rats were measured at 30,60,120,and 240 min after intraperitoneal injection of 50%glucose solution(4 mL·kg-1)to evaluate glu-cose tolerance.The serum insulin level of the rats was detected by ELISA and the insulin resistance index was calculated.The blood biochemical parameters were measured by an automatic blood biochemical analyzer.HE staining was used to evaluate the pathological conditions of the liver and pancreatic tissues of the rats.Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was used for mass spectrometry detection to identify differential metabolites,and MetaboAnalyst 5.0 was used for pathway enrichment analysis.RESULTS Compared with the blank group,the fasting blood glucose,area under the glucose tolerance curve,and insulin resistance index of the model group rats were significantly increased(P<0.001),blood TP and GLB were significantly de-creased(P<0.01),AST,ALT,and ALP were significantly increased(P<0.05,P<0.01,P<0.001),and obvious inflammatory cell infiltration and pathological damage were observed in the liver and pancreas tissues;compared with the model group,the fasting blood glucose,area under the glucose tolerance curve,and insulin resistance index of the acupuncture-medicine combination group were sig-nificantly decreased(P<0.05,P<0.01,P<0.001),blood ALP was significantly decreased(P<0.01),TP and GLB were significant-ly increased(P<0.05),and the pathological damage of the liver and pancreas was significantly improved.Serum metabolomics showed that the metabolic profiles of the groups were well distinguished.Compared with the blank group,the differential metabolites in the model group were enriched in histidine metabolism,thiamine metabolism,taurine and hypotaurine metabolism,ascorbic acid and alde-hyde ester metabolism,valine,leucine and isoleucine biosynthesis pathways;compared with the model group,237 metabolites such as 3-aminoadipic acid,3-oxocyclobutanecarboxylic acid and phosphorylcholine in the acupuncture-medicine combination group were sig-nificantly reduced,and the pathways were enriched in histidine metabolism,linoleic acid metabolism,thiamine metabolism,taurine and hypotaurine metabolism,valine,leucine and isoleucine biosynthesis pathways.CONCLUSION Electroacupuncture combined with metformin can effectively improve the glucose and lipid metabolism of T2DM rats,and its potential mechanism may be related to the regulation of amino acid metabolism.

OBJECTIVE: To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice. METHODS: BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues. RESULTS: BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation. CONCLUSION The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Animals ; Mice ; Mesenchymal Stem Cell Transplantation ; Liver Cirrhosis/etiology* ; Male ; Cholestasis/therapy* ; Mice, Inbred C57BL ; Hepatic Stellate Cells ; Mesenchymal Stem Cells

In the development of traditional Chinese medicine(TCM), the concept of "preventive treatment of disease" has a long history and plays a crucial role in bridging the past and the future. With the continuous growth of public health needs and the ongoing transformation of the registration management of TCM, its position in the research and development of new drugs has become increasingly significant. As one of the important sources of new drug innovation, the new TCM for "preventive treatment of diseases" represents a new thinking proposed based on the current routine registration and research and development. The research and development of TCM for "preventive treatment of diseases" mainly cover four stages: prevention(before the onset of disease), early intervention(when the disease is about to occur), interruption and reversal(when the disease has already occurred), and prevention of recurrence after recovery(after the disease). This study aims to comprehensively analyze the positioning, key points, and difficulties in the research and development of TCM for "preventive treatment of diseases" and explore effective paths to promote the innovative development of TCM through relevant cases. The research and development of new TCM for "preventive treatment of disease" require researchers to seize the opportunities for innovation before the start of the research and development, accurately grasp the key issues at different stages, and pay attention to the full lifecycle evaluation of the drugs. Meanwhile, in the design of the research plan, the optimal effectiveness evaluation indicators should be explored; key and difficult areas such as chronic diseases and rare diseases should be taken seriously, and the limitations of new drug development only based on the diagnosed diseases should be broken, so as to cater to more patients. In addition, through relevant representative cases in China and abroad, the unique advantages of TCM for "preventive treatment of diseases" should be fully leveraged. By learning from the past, all aspects of key points in the evaluation of new drug research and development should be strengthened. Finally, this study proposed that TCM for "preventive treatment of diseases" can employ novel methods and advanced technologies such as new biomarkers and innovative clinical design protocols, as well as new perspectives on disease research and health management. This can provide new paths for the innovation of TCM and public health management.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pharmacy Research

Fritillariae Cirrhosae Bulbus is the dried bulb of perennial herbaceous plants in the Fritillaria genus(Liliaceae family) and is a representative traditional Chinese medicinal material with distinctive regional characteristics. Clinically, it is widely used in the treatment of dry cough, bronchial asthma, and other respiratory diseases, possessing significant medicinal and economic value and being highly esteemed in TCM. Currently, Fritillariae Cirrhosae Bulbus primarily relies on wild harvesting. However, due to excessive collection, its wild resources have drastically declined, and all source species have been classified as category Ⅱ in the List of National Key Protected Wild Plants, exacerbating the supply-demand imbalance in the market. To mitigate this issue, large-scale cultivation through the domestication of wild Fritillariae Cirrhosae Bulbus has become an inevitable trend. However, its strict environmental requirements, low propagation efficiency, high seedling mortality, and immature cultivation techniques have severely hindered industrialization. This study investigates the domestication process of Fritillariae Cirrhosae Bulbus, focusing on seed propagation, seedling cultivation, and medicinal material production. It also reviews the species and distribution of wild resources, their endangered status, market supply-demand dynamics, and the historical and current development of domestication. The findings indicate that enhancing propagation efficiency, optimizing cultivation models, and distinguishing between seed propagation and medicinal material production are key measures to accelerate the industrialization of domesticated Fritillariae Cirrhosae Bulbus. This research aims to promote the industrialization of Fritillariae Cirrhosae Bulbus domestication and provide a reference model for the conservation and sustainable utilization of rare and endangered medicinal plant resources.
Fritillaria/chemistry* ; Endangered Species ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/economics* ; China

Objective:To analyze the prospective associations between liver biomarkers and mortality among Chinese middle-aged and elderly populations and to evaluate the mortality risk predictive value.Methods:A total of 22 758 participants from the 3 rd resurvey of the China Kadoorie Biobank were included. Cox proportional hazard models were used to analyze the prospective associations of 5 liver biomarkers with mortality. These liver biomarkers included two liver imaging biomarkers (liver fat attenuation parameter, liver stiffness measurement) and three serum liver enzyme biomarkers [gamma-glutamyl transferase (GGT), ALT, and AST]. Restricted cubic spline was used to assess the nonlinear associations between biomarkers and mortality. The area used the receiver operating characteristic curve (AUC) to evaluate the predictive ability of the models after incorporating liver biomarkers into traditional prediction models for mortality. Results:The mean age of the participants was (65.2±9.1) years, with a median follow-up of 1.5 years, during which 307 deaths occurred. Compared to individuals without hepatic steatosis, those with severe hepatic steatosis had a 79% higher risk of mortality, with a HR of 1.79 (95% CI: 1.06-3.03). Compared to individuals without hepatic fibrosis, those with advanced fibrosis and cirrhosis had higher mortality risks of 48% and 91%, respectively (both P<0.05). For each standard deviation increase in GGT, the mortality risk increased by 10% ( HR=1.10, 95% CI: 1.05-1.15), with the positive association plateauing at higher GGT levels. AST exhibited a U-shaped association with mortality risk. The AUC of the prediction model adding liver biomarkers into traditional prediction factors was 0.718 (95% CI: 0.679-0.757), with an increase of 0.030 ( P<0.001) compared with the traditional model. Conclusions:Severe hepatic steatosis, higher levels of hepatic fibrosis, and elevated GGT levels are significantly associated with higher mortality risk. AST shows a U-shaped nonlinear association with mortality risk. Incorporating liver biomarkers into traditional risk prediction models enhance the ability to predict mortality.

Objective:To investigate the prospective associations between plasma metabolites and the risks of all-cause and cause-specific mortality among Chinese adults.Methods:This study analyzed plasma metabolomics data from 2 183 healthy adults in the China Kadoorie Biobank (CKB), measured using targeted mass spectrometry. Cox proportional hazards regression models were used to examine the associations between 630 metabolites and the risk of all-cause mortality. Cause-specific hazard regression models evaluated the associations between metabolites and cardiovascular disease (CVD) risks, cancer, and other-cause mortality. Stepwise regression was used to identify key metabolites independently associated with all-cause mortality, and the area under the receiver operating characteristic curve (AUC) was calculated to assess the improvement in predictive performance when these metabolites were added to traditional risk prediction models.Results:The mean age of the participants was (53.2±9.8) years, 65.1% of whom were female. During a median follow-up of 14.5 years, 231 deaths occurred. A total of 44 metabolites were significantly associated with the risk of all-cause mortality [false discovery rate (FDR)-adjusted P<0.05], primarily including triglycerides, ceramides, and amino acids. Additionally, 29 and 15 metabolites were found to be associated with cancer and other-cause mortality, respectively, but no metabolites were significantly associated with CVD mortality after FDR corrections. Adding 14 metabolites independently associated with all-cause mortality into the traditional prediction model significantly improved its predictive performance. Specifically, incorporating metabolites into the traditional model, which already included laboratory biomarkers, increased the AUC to 0.798 (95% CI: 0.755-0.843), an improvement of 0.088 compared to the traditional model ( P<0.001). Conclusions:Multiple metabolites are significantly associated with mortality risk and can substantially improve the accuracy of mortality risk prediction models. These findings provide new insights into the physiological mechanisms of aging and offer valuable clues for personalized health risk assessment.