BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

BACKGROUND:In recent years,a number of studies have confirmed that gut microbiome regulates bone metabolism through multiple pathways,and this field has become a research hotspot in orthopedics and microbiology.However,there is still no literature metrology and visual analysis on this field.OBJECTIVE:To explore the research status,hot spots and development trends in the field of gut microbiome regulation of bone metabolism,and to provide certain data support and reference for subsequent studies.METHODS:The Web of Science core collection database was used as the retrieval platform to retrieve the related literature in the field of intestinal flora regulating bone metabolism from 2004 to 2024.Citespace software was used to visually analyze the included literature and generate a visual atlas.RESULTS AND CONCLUSION:(1)A total of 1,035 papers were included in this study.In the past 20 years,the number of publications in the field of gut microbiome regulation of bone metabolism has shown a significant growth trend,with the United States and China dominating research and publication activities in this field.Harvard University and the University of California system are the research institutions with the highest number of published papers and research centrality in this area,and Professor Pacifici R of Emory University is the most prolific author.(2)Inflammatory bowel disease,chain fatty acids,bone marrow are the core keywords in this field.Postmenopausal osteoporosis,rheumatoid arthritis,oxidative stress,mitochondrial dysfunction are the latest research frontiers in this field.(3)Among the top 10 cited papers,4 discussed the mechanism of short-chain fatty acids affecting bone metabolism;3 investigated the pathogenesis and therapeutic potential of intestinal flora in postmenopausal osteoporosis,glucocorticoid-induced osteoporosis,and senile osteoporosis;1 discussed the relationship between intestinal inflammation,intestinal flora,parathyroid hormone,and bone metabolism;and 1 examined the effects of Lactobacillus rhamnosus and T cells on the gut microbiome and bone metabolism.(4)NUTRIENTS has the most papers,while ENDOCRINOLOGY& METABOLISM has the most citations.(5)Based on literature co-citation analysis and keywords,further exploration is needed on the specific pathogenesis and treatment strategies of gut microbiome in postmenopausal osteoporosis and rheumatoid arthritis,revealing the molecular mechanism of regulating gut microbiota to inhibit oxidative stress and improve mitochondrial dysfunction affecting bone metabolism,and translating mechanism research into clinical application,which all constitute the future research directions and trends in this field.

BACKGROUND:In recent years,postmenopausal osteoporosis has been widely concerned by the society.With the gradual deepening of the research on animal models,animal models have become an important means of modern traditional Chinese medicine research as well as the experimental basis.Therefore,it is particularly important to understand the current status,hotspots,and development trend of the research on animal models.OBJECTIVE:To analyze the research status,hotspots,and development trend of animal models of postmenopausal osteoporosis at home and abroad,and to provide a certain theoretical foundation and reference basis for subsequent research.METHODS:Using"Subject=Postmenopausal osteoporosis AND Subject line=Mouse+Rabbit+Dog+Pig+Sheep+Monkey+Fish+Laboratory animals+Animal experimentation"in Chinese as the search formula,we searched for relevant literature published from January 1,1999 to October 1,2023 in CNKI and WanFang databases.Meanwhile,the articles published from January 1,1999 to October 1,2023 in the Web of Science Core Collection database were searched using"TS=(Postmenopausal osteoporosis)AND TS=(mouse OR mice OR rat OR rabbit OR dog OR swine OR pig OR sheep OR monkey OR fish OR flies OR"laboratory animal"OR"experiment animal"as the search formula.CiteSpace software was applied to visualize and analyze the authors,institutions,countries,keywords,and literature co-citations.RESULTS AND CONCLUSION:(1)After analyzing and screening,1 238 documents were included in the CNKI and WanFang databases,and 3 419 documents were included in the Web of Science Core Collection database.The overall number of articles issued since 1999 has been on an upward trend,with the highest research centrality in the United States,the highest number of articles issued in China.Moreover,the institution with the highest research centrality is the University of California.(2)After removing the keywords directly related to the article topics and synthesizing the co-occurrence frequency and centrality,"biomechanics,""Zuo Gui Wan,""alendronate,""breast cancer,"and"biochemical indicators"are in the core of the research field.(3)According to the analysis of co-citations,among the top 10 cited documents,5 of them are related to the treatment measures and clinical efficacy of postmenopausal osteoporosis.(4)Based on the analysis of keywords and co-cited literature,investigations on osteoblast formation and the mechanism of bone formation,the mechanism of metabolomics,the treatment of traditional Chinese medicine,signaling pathway,parathyroid hormone treatment,and sclerostin antibody treatment are the hot research topics now and the future research trends.

Objective:To analyze suicide methods and demographic characteristics of attempted suicide pa-tients in Baise City,Guangxi and to provide the basis for suicide intervention.Methods:A retrospective analysis method was conducted on the case data of attempted suicide patients treated in the emergency departments of 14 general hospitals in Baise City from 2018 to 2021.The situation of attempted suicide patients was recorded using the suicide patient information collection forms.Results:Among the 2 529 attempted suicide patients,1 636 committed-suicide by taking pesticides,557 used therapeutic drugs,112 used rodenticides,and 53 used carbonmonoxide(CO).The proportion of male and farmer suicides by taking pesticides was higher,and the proportion of female and non-farmer suicides by taking therapeutic drugs was higher.Multivariate analysis showed that the proportion of patients aged 45-60 years old patients who took pesticide was higher(OR=3.18),while the proportion of patients aged 45～60 who took therapeutic drugs was lower(OR=0.19).The proportion of suicides taking pesticides and using carbon monoxide significantly decreased in 2020(OR=0.56)and 2021(OR=0.52),while the proportion of sui-cides taking therapeutic drugs significantly increased in 2020(OR=2.04)and 2021(OR=3.18).Conclusion:Proportion of attempted suicide by taking pesticides is the most common method of suicide among residents in Baise City,with males,farmers,and middle-aged groups being the most affected.The proportion of attempted suicide by taking medication has significantly increased,with a higher incidence among women.

Objective:To analyze suicide methods and demographic characteristics of attempted suicide pa-tients in Baise City,Guangxi and to provide the basis for suicide intervention.Methods:A retrospective analysis method was conducted on the case data of attempted suicide patients treated in the emergency departments of 14 general hospitals in Baise City from 2018 to 2021.The situation of attempted suicide patients was recorded using the suicide patient information collection forms.Results:Among the 2 529 attempted suicide patients,1 636 committed-suicide by taking pesticides,557 used therapeutic drugs,112 used rodenticides,and 53 used carbonmonoxide(CO).The proportion of male and farmer suicides by taking pesticides was higher,and the proportion of female and non-farmer suicides by taking therapeutic drugs was higher.Multivariate analysis showed that the proportion of patients aged 45-60 years old patients who took pesticide was higher(OR=3.18),while the proportion of patients aged 45～60 who took therapeutic drugs was lower(OR=0.19).The proportion of suicides taking pesticides and using carbon monoxide significantly decreased in 2020(OR=0.56)and 2021(OR=0.52),while the proportion of sui-cides taking therapeutic drugs significantly increased in 2020(OR=2.04)and 2021(OR=3.18).Conclusion:Proportion of attempted suicide by taking pesticides is the most common method of suicide among residents in Baise City,with males,farmers,and middle-aged groups being the most affected.The proportion of attempted suicide by taking medication has significantly increased,with a higher incidence among women.

BACKGROUND:In recent years,a number of studies have confirmed that gut microbiome regulates bone metabolism through multiple pathways,and this field has become a research hotspot in orthopedics and microbiology.However,there is still no literature metrology and visual analysis on this field.OBJECTIVE:To explore the research status,hot spots and development trends in the field of gut microbiome regulation of bone metabolism,and to provide certain data support and reference for subsequent studies.METHODS:The Web of Science core collection database was used as the retrieval platform to retrieve the related literature in the field of intestinal flora regulating bone metabolism from 2004 to 2024.Citespace software was used to visually analyze the included literature and generate a visual atlas.RESULTS AND CONCLUSION:(1)A total of 1,035 papers were included in this study.In the past 20 years,the number of publications in the field of gut microbiome regulation of bone metabolism has shown a significant growth trend,with the United States and China dominating research and publication activities in this field.Harvard University and the University of California system are the research institutions with the highest number of published papers and research centrality in this area,and Professor Pacifici R of Emory University is the most prolific author.(2)Inflammatory bowel disease,chain fatty acids,bone marrow are the core keywords in this field.Postmenopausal osteoporosis,rheumatoid arthritis,oxidative stress,mitochondrial dysfunction are the latest research frontiers in this field.(3)Among the top 10 cited papers,4 discussed the mechanism of short-chain fatty acids affecting bone metabolism;3 investigated the pathogenesis and therapeutic potential of intestinal flora in postmenopausal osteoporosis,glucocorticoid-induced osteoporosis,and senile osteoporosis;1 discussed the relationship between intestinal inflammation,intestinal flora,parathyroid hormone,and bone metabolism;and 1 examined the effects of Lactobacillus rhamnosus and T cells on the gut microbiome and bone metabolism.(4)NUTRIENTS has the most papers,while ENDOCRINOLOGY& METABOLISM has the most citations.(5)Based on literature co-citation analysis and keywords,further exploration is needed on the specific pathogenesis and treatment strategies of gut microbiome in postmenopausal osteoporosis and rheumatoid arthritis,revealing the molecular mechanism of regulating gut microbiota to inhibit oxidative stress and improve mitochondrial dysfunction affecting bone metabolism,and translating mechanism research into clinical application,which all constitute the future research directions and trends in this field.

BACKGROUND:In recent years,postmenopausal osteoporosis has been widely concerned by the society.With the gradual deepening of the research on animal models,animal models have become an important means of modern traditional Chinese medicine research as well as the experimental basis.Therefore,it is particularly important to understand the current status,hotspots,and development trend of the research on animal models.OBJECTIVE:To analyze the research status,hotspots,and development trend of animal models of postmenopausal osteoporosis at home and abroad,and to provide a certain theoretical foundation and reference basis for subsequent research.METHODS:Using"Subject=Postmenopausal osteoporosis AND Subject line=Mouse+Rabbit+Dog+Pig+Sheep+Monkey+Fish+Laboratory animals+Animal experimentation"in Chinese as the search formula,we searched for relevant literature published from January 1,1999 to October 1,2023 in CNKI and WanFang databases.Meanwhile,the articles published from January 1,1999 to October 1,2023 in the Web of Science Core Collection database were searched using"TS=(Postmenopausal osteoporosis)AND TS=(mouse OR mice OR rat OR rabbit OR dog OR swine OR pig OR sheep OR monkey OR fish OR flies OR"laboratory animal"OR"experiment animal"as the search formula.CiteSpace software was applied to visualize and analyze the authors,institutions,countries,keywords,and literature co-citations.RESULTS AND CONCLUSION:(1)After analyzing and screening,1 238 documents were included in the CNKI and WanFang databases,and 3 419 documents were included in the Web of Science Core Collection database.The overall number of articles issued since 1999 has been on an upward trend,with the highest research centrality in the United States,the highest number of articles issued in China.Moreover,the institution with the highest research centrality is the University of California.(2)After removing the keywords directly related to the article topics and synthesizing the co-occurrence frequency and centrality,"biomechanics,""Zuo Gui Wan,""alendronate,""breast cancer,"and"biochemical indicators"are in the core of the research field.(3)According to the analysis of co-citations,among the top 10 cited documents,5 of them are related to the treatment measures and clinical efficacy of postmenopausal osteoporosis.(4)Based on the analysis of keywords and co-cited literature,investigations on osteoblast formation and the mechanism of bone formation,the mechanism of metabolomics,the treatment of traditional Chinese medicine,signaling pathway,parathyroid hormone treatment,and sclerostin antibody treatment are the hot research topics now and the future research trends.

BACKGROUND:With the variation of disease treatment modes and the in-depth research on senile osteoporosis in recent years,increasing studies have confirmed that traditional Chinese medicine has a significant effect on the prevention and treatment of senile osteoporosis. OBJECTIVE:To investigate the effect of Yishen Gushu Formula on bone metabolic markers in patients with osteoporosis of kidney deficiency and blood stasis type. METHODS:102 patients with senile osteoporosis of kidney deficiency and blood stasis type who were treated at Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2020 to March 2022 were enrolled,including 32 males and 70 females,aged 71-93 years.All patients were randomly divided into two groups,with 51 patients in each group.The control group was treated with calcium carbonate D3 granules and sodium alendronate tablets,while the treatment group was treated with Yishen Gushu Formula beyond the control group.Treatments in each group lasted 3 months.Bone mineral density of the L1-4 lumbar vertebrae and left femoral neck,visual analog scale score,and serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were measured before and 3 months after treatment.Traditional Chinese medicine syndrome score and therapeutic efficiency were also assessed. RESULTS AND CONCLUSION:After 3 months of treatment,the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly increased in both two groups(P<0.05),and the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly higher in the treatment group than the control group(P<0.05).The visual analog scale scores of both groups after 3 months of treatment were lower than those before treatment(P<0.05),and the visual analog scores of the treatment group after 3 months of treatment were lower than those of the control group(P<0.05).After 3 months of treatment,the serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly improved in both two groups,while compared with the control group,the serum levels of osteocalcin and osteopontin were significantly higher(P<0.05)and the serum levels of type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly lower in the treatment group(P<0.05).After 3 months of treatment,the Traditional Chinese medicine syndrome scores were decreased in both two groups,while the Traditional Chinese medicine syndrome scores in the treatment group were lower than those in the control group.After 3 months of treatment,no significant adverse reactions occurred in both groups.The total effective rate was 88.2%and 70.6%in the treatment and control groups respectively,and there was a significant difference between the two groups(P<0.05).To conclude,Yishen Gushu Formula combined with anti-osteoporosis drugs can significantly improve the clinical symptoms of patients with senile osteoporosis of kidney deficiency and blood stasis type and prevent disease progression by regulating bone metabolism,increasing bone mineral density,and relieving pain.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.