BACKGROUND:Studies have shown that there is a close relationship between pyroptosis,inflammatory factors and osteoporosis.OBJECTIVE:To review the effects of pyroptosis and inflammatory factors on the pathogenesis of osteoporosis from the perspectives of osteogenic differentiation and osteoclastic differentiation,based on an overview of pyroptosis in relation to the interaction of relevant inflammatory factors.METHODS:The first author used the computer to search the literature published by each database until 2024,and searched CNKI,WanFang,VIP and PubMed databases with the search terms of"pyroptosis,inflammatory factors,osteoporosis,osteoblast,osteoclast,bone metabolism,signaling pathway,review"in Chinese and English.A total of 79 papers were finally included according to the inclusion criteria.RESULTS AND CONCLUSION:The progression of osteoporosis is closely related to inflammation,in which pyroptosis plays a key role.Immune cells induce pyroptosis through apoptosis pathway,promote the secretion of inflammatory factors such as interleukin-18,interleukin-1β and NLRP3,build an inflammatory immune microenvironment,and regulate bone metabolism through complex signaling pathways,resulting in enhanced bone absorption and reduced bone formation,thereby leading to osteoporosis.Previous studies have shown that inhibiting pyroptosis is anti-inflammatory and slows the progression of osteoporosis,and it has been shown to improve inflammatory bone loss in vitro and in animal models.At present,research on pyroptosis and osteoporosis is limited.On the one hand,the exact mechanism of osteoporosis and the pathogenesis of pyroptosis are unknown,and the specific pathways and regulatory mechanisms remain to be understood.On the other hand,therapeutic strategies targeting pyroptosis are still theoretical,not clinically proven,and drug side effects are unknown.In the future,the research focus is to further explore the pathogenesis,especially the mechanism of pyroptosis,identify potential therapeutic targets,further study the pyroptosis signaling pathway and Gasdermin protein,and develop new drugs to improve the therapeutic effect in patients with osteoporosis.

BACKGROUND:Studies have shown that there is a close relationship between pyroptosis,inflammatory factors and osteoporosis.OBJECTIVE:To review the effects of pyroptosis and inflammatory factors on the pathogenesis of osteoporosis from the perspectives of osteogenic differentiation and osteoclastic differentiation,based on an overview of pyroptosis in relation to the interaction of relevant inflammatory factors.METHODS:The first author used the computer to search the literature published by each database until 2024,and searched CNKI,WanFang,VIP and PubMed databases with the search terms of"pyroptosis,inflammatory factors,osteoporosis,osteoblast,osteoclast,bone metabolism,signaling pathway,review"in Chinese and English.A total of 79 papers were finally included according to the inclusion criteria.RESULTS AND CONCLUSION:The progression of osteoporosis is closely related to inflammation,in which pyroptosis plays a key role.Immune cells induce pyroptosis through apoptosis pathway,promote the secretion of inflammatory factors such as interleukin-18,interleukin-1β and NLRP3,build an inflammatory immune microenvironment,and regulate bone metabolism through complex signaling pathways,resulting in enhanced bone absorption and reduced bone formation,thereby leading to osteoporosis.Previous studies have shown that inhibiting pyroptosis is anti-inflammatory and slows the progression of osteoporosis,and it has been shown to improve inflammatory bone loss in vitro and in animal models.At present,research on pyroptosis and osteoporosis is limited.On the one hand,the exact mechanism of osteoporosis and the pathogenesis of pyroptosis are unknown,and the specific pathways and regulatory mechanisms remain to be understood.On the other hand,therapeutic strategies targeting pyroptosis are still theoretical,not clinically proven,and drug side effects are unknown.In the future,the research focus is to further explore the pathogenesis,especially the mechanism of pyroptosis,identify potential therapeutic targets,further study the pyroptosis signaling pathway and Gasdermin protein,and develop new drugs to improve the therapeutic effect in patients with osteoporosis.

This paper summarizes Professor WANG Yaoxian's experience in treating diabetic kidney disease （DKD） from the perspective of spleen and stomach based on the "internal heat leading to concretions" theory. It is considered that internal heat leading to concretions constitutes the core pathogenesis of DKD， with the spleen and stomach serving as the source of internal heat； therefore， treatment should be based on regulating the spleen and stomach. In the early stage of DKD， dysfunction of the spleen and stomach leads to the initial generation of internal heat. Common syndrome patterns include gastrointestinal heat accumulation and constrained heat in the liver and stomach， for which modified Gegen Qinlian Decoction （葛根芩连汤） can be used to clear heat bind while modified Dachaihu Decoction （大柴胡汤） is used to clear stomach and soothe liver， respectively. In the middle stage of DKD， weakness of the spleen and stomach results in the initial formation of concretions and conglomerations. Common patterns include spleen deficiency with prevalence of dampness and deficiency of both the spleen and kidney. Treatment emphasizes strengthening the spleen and resolving dampness， raising yang and boosting the stomach with modified Shengyang Yiwei Decoction （升阳益胃汤）， or supplementing spleen and boosting kidney， dissipating bind and dispe-ring concretions with modified Shenqi Dihuang Decoction （参芪地黄汤）， respectively. In the late stage of DKD， it is characterized by spleen and stomach depletion， and rampant accumulation of turbidity and toxin， and the common syndrome patterns are damp-turbidity obstruction in the middle jiao （焦） and spleen-kidney yang deficiency. Treatment aims to remove turbidity and harmonize the stomach， or to warm the kidney and strengthen the spleen while elimina-ting turbidity， using modified Dahuang Gancao Decoction（大黄甘草汤） and Jupi Zhuru Decoction （橘皮竹茹汤） or modified Baoyuan Decoction （保元汤） and Lizhong Decoction （理中汤）， respectively. In clinical practice， appropriate formulas and medications are flexibly selected according to specific syndromes.

Osteoarthritis(OA)is a common joint disease in clinical practice,and cartilage damage is a typical pathological change.The pathogenesis of OA is complex,and various adverse factors can lead to the occurrence of OA.Mitochondria are im-portant organelles within cells and play important roles in cellular physiological and pathological activ-ities.Mitochondrial quality control is an important regulatory mechanism in the body to maintain nor-mal mitochondrial structure and function,mainly including mitochondrial biogenesis,mitochondrial dynamics,mitochondrial autophagy,mitochondrial oxidative stress,and other forms.The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis,and regulating the balance of mi-tochondrial quality control is a potential therapeu-tic point for osteoarthritis.The author reviewed rel-evant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and develop-ment of osteoarthritis,in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis.

Objective:To analyze the efficacy of total knee arthroplasty (TKA) with partial varus retention in the treatment of moderate knee varus.Methods:A retrospective analysis was conducted on the data of 613 osteoarthritis patients with moderate knee varus who underwent TKA at the First Affiliated Hospital of Nanjing Medical University from January 2010 to October 2019. According to whether a 2°-3° of knee varus was retained, the patients were divided into the retained varus group and the mechanical alignment group. The retained varus group included 318 cases, with 63 males and 255 females, aged 68.51±6.95 years (range, 46-86 years), and BMI of 26.99±3.66 kg/m 2 (range, 17.40-39.01 kg/m 2). Preoperative Kellgren-Lawrence (K-L) classification of knee osteoarthritis was grade III in 113 cases and grade IV in 205 cases. The mechanical alignment group included 295 cases, with 75 males and 220 females, aged 69.60±7.12 years (range, 52-87 years), and BMI of 26.95±3.94 kg/m 2 (range, 16.60-41.90 kg/m 2). Preoperative K-L classification was grade III in 102 cases and grade IV in 193 cases. Surgical duration, total blood loss, preoperative and postoperative varus angle, lower limb swelling on the fifth postoperative day, and postoperative complications were recorded. Follow-up were arranged at 3 months, 6 months, 1 year, and 5 years postoperatively. At each follow-up point, the visual analogue score (VAS) for knee pain, Hospital for Special Surgery (HSS) score, Forgotten Joint Score (FJS-12), and MOS item short-form health survey (SF-36) were assessed. Results:All 613 patients were successfully followed up, with a follow-up period of 5.25±1.02 years (range, 5.0-6.0 years). There were no statistically significant differences in gender, age, BMI, and K-L classification between the two groups ( P>0.05). The differences in postoperative varus angle, VAS scores, and HSS score were statistically significant from the preoperative values in both groups( P<0.05). The surgical duration of the retained varus group was 77.40±18.55 min, total blood loss was 920.78±407.26 ml, and lower limb swelling on the fifth postoperative day was 1.18±0.51 cm, all of which were lower than those in the mechanical alignment group: 85.31±22.15 min, 1127.14±580.08 ml, 3.22±0.52 cm, respectively, with statistically significant differences ( P<0.05). The VAS scores at postoperative day 5 and 3 months in the retained varus group were 5.08±0.72 and 2.18±1.09, respectively, which were lower than those in the mechanical alignment group: 5.80±0.81, 3.00±1.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in VAS scores at 6 months, 1 year, and 5 years postoperatively between the two groups ( P>0.05). The HSS scores at 3 months and 6 months postoperatively in the retained varus group were 68.57±4.98 and 79.04±3.26, respectively, which were higher than those in the mechanical alignment group: 64.14±3.99, 77.73±4.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in HSS scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The FJS-12 scores at 3 months and 6 months postoperatively in the retained varus group were 18.06±3.50 and 27.50±1.80, respectively, which were higher than those in the mechanical alignment group: 13.45±2.44, 24.23±1.59, with statistically significant differences ( P<0.05). There were no statistically significant differences in FJS-12 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The SF-36 scores at 3 months and 6 months postoperatively in the retained varus group were 40.85±8.07 and 52.15±6.01, respectively, which were higher than those in the mechanical alignment group: 35.87±6.83, 47.28±5.38, with statistically significant differences ( P<0.05). There were no statistically significant differences in SF-36 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The incidence of deep vein thrombosis in the lower limbs was 3.8% (12/318) in the retained varus group, which was lower than the 7.8% (23/295) in the mechanical alignment group, with a statistically significant difference ( P<0.05). Conclusion:In osteoarthritis patients with moderate knee varus undergoing TKA, retaining approximately 3° of varus can reduce surgical trauma and total blood loss, shorten surgical duration, alleviate postoperative pain and limb swelling, facilitate functional recovery, and improve patient satisfaction.

Objective To establish a predictive nomogram model for diabetic peripheral neuropathy(DPN)in elderly diabetic patients.Methods A total of 200 elderly patients with T2DM admitted to our hospital were enrolled in this study from January 2021 to October 2023.All the patients were divided into a simple T2DM group(n=160)and a T2DM combined with DPN(DPN,n=40)group.The general data and biochemical indexes were compared between the two groups.Spearman correlation analysis was used to explore the correlation between clinical indicators and the occurrence of DPN in the elderly.Logistic regression was used to analyze the influencing factors for DPN in the elderly,and a nomogram was constructed.The receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of the model.Results The DM duration,DR and HbA1c were higher(P<0.05),while HDL-C was lower in the DPN group than in the T2DM group(P<0.05).Spearman correlation analysis showed that elderly DPN were positively correlated with DR,DM duration and HbA1c(r=0.456,0.565,0.580,P<0.05),and negatively correlated with HDL-C(r=-0.542,P<0.05).Logistic regression analysis showed that DR(OR 1.035,95%CI 1.032～1.040),DM duration(OR 1.070,95%CI 1.045～1.080),HbA1c(OR 1.235,95%CI 1.156～1.280)and HDL-C(OR 0.895,95%CI 0.877～0.950)were both influencing factors for elderly DPN.A nomogram prediction model for elderly DPN was constructed based on DR,DM duration,HbA1c and HDL-C.ROC curve analysis showed that the area under curve of this prediction model was 0.955,with a sensitivity of 92.50%,a specificity of 95.00%,and a cutoff value of 0.251.Conclusions The established predictive diagram model involves four variables,including DR,DM duration,HbA1c and HDL-C,which can assist the clinic to make an early assessment of DPN risk.

Osteoarthritis(OA)is a common joint disease in clinical practice,and cartilage damage is a typical pathological change.The pathogenesis of OA is complex,and various adverse factors can lead to the occurrence of OA.Mitochondria are im-portant organelles within cells and play important roles in cellular physiological and pathological activ-ities.Mitochondrial quality control is an important regulatory mechanism in the body to maintain nor-mal mitochondrial structure and function,mainly including mitochondrial biogenesis,mitochondrial dynamics,mitochondrial autophagy,mitochondrial oxidative stress,and other forms.The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis,and regulating the balance of mi-tochondrial quality control is a potential therapeu-tic point for osteoarthritis.The author reviewed rel-evant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and develop-ment of osteoarthritis,in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis.

Objective:To analyze the efficacy of total knee arthroplasty (TKA) with partial varus retention in the treatment of moderate knee varus.Methods:A retrospective analysis was conducted on the data of 613 osteoarthritis patients with moderate knee varus who underwent TKA at the First Affiliated Hospital of Nanjing Medical University from January 2010 to October 2019. According to whether a 2°-3° of knee varus was retained, the patients were divided into the retained varus group and the mechanical alignment group. The retained varus group included 318 cases, with 63 males and 255 females, aged 68.51±6.95 years (range, 46-86 years), and BMI of 26.99±3.66 kg/m 2 (range, 17.40-39.01 kg/m 2). Preoperative Kellgren-Lawrence (K-L) classification of knee osteoarthritis was grade III in 113 cases and grade IV in 205 cases. The mechanical alignment group included 295 cases, with 75 males and 220 females, aged 69.60±7.12 years (range, 52-87 years), and BMI of 26.95±3.94 kg/m 2 (range, 16.60-41.90 kg/m 2). Preoperative K-L classification was grade III in 102 cases and grade IV in 193 cases. Surgical duration, total blood loss, preoperative and postoperative varus angle, lower limb swelling on the fifth postoperative day, and postoperative complications were recorded. Follow-up were arranged at 3 months, 6 months, 1 year, and 5 years postoperatively. At each follow-up point, the visual analogue score (VAS) for knee pain, Hospital for Special Surgery (HSS) score, Forgotten Joint Score (FJS-12), and MOS item short-form health survey (SF-36) were assessed. Results:All 613 patients were successfully followed up, with a follow-up period of 5.25±1.02 years (range, 5.0-6.0 years). There were no statistically significant differences in gender, age, BMI, and K-L classification between the two groups ( P>0.05). The differences in postoperative varus angle, VAS scores, and HSS score were statistically significant from the preoperative values in both groups( P<0.05). The surgical duration of the retained varus group was 77.40±18.55 min, total blood loss was 920.78±407.26 ml, and lower limb swelling on the fifth postoperative day was 1.18±0.51 cm, all of which were lower than those in the mechanical alignment group: 85.31±22.15 min, 1127.14±580.08 ml, 3.22±0.52 cm, respectively, with statistically significant differences ( P<0.05). The VAS scores at postoperative day 5 and 3 months in the retained varus group were 5.08±0.72 and 2.18±1.09, respectively, which were lower than those in the mechanical alignment group: 5.80±0.81, 3.00±1.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in VAS scores at 6 months, 1 year, and 5 years postoperatively between the two groups ( P>0.05). The HSS scores at 3 months and 6 months postoperatively in the retained varus group were 68.57±4.98 and 79.04±3.26, respectively, which were higher than those in the mechanical alignment group: 64.14±3.99, 77.73±4.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in HSS scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The FJS-12 scores at 3 months and 6 months postoperatively in the retained varus group were 18.06±3.50 and 27.50±1.80, respectively, which were higher than those in the mechanical alignment group: 13.45±2.44, 24.23±1.59, with statistically significant differences ( P<0.05). There were no statistically significant differences in FJS-12 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The SF-36 scores at 3 months and 6 months postoperatively in the retained varus group were 40.85±8.07 and 52.15±6.01, respectively, which were higher than those in the mechanical alignment group: 35.87±6.83, 47.28±5.38, with statistically significant differences ( P<0.05). There were no statistically significant differences in SF-36 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The incidence of deep vein thrombosis in the lower limbs was 3.8% (12/318) in the retained varus group, which was lower than the 7.8% (23/295) in the mechanical alignment group, with a statistically significant difference ( P<0.05). Conclusion:In osteoarthritis patients with moderate knee varus undergoing TKA, retaining approximately 3° of varus can reduce surgical trauma and total blood loss, shorten surgical duration, alleviate postoperative pain and limb swelling, facilitate functional recovery, and improve patient satisfaction.

Objective To establish a predictive nomogram model for diabetic peripheral neuropathy(DPN)in elderly diabetic patients.Methods A total of 200 elderly patients with T2DM admitted to our hospital were enrolled in this study from January 2021 to October 2023.All the patients were divided into a simple T2DM group(n=160)and a T2DM combined with DPN(DPN,n=40)group.The general data and biochemical indexes were compared between the two groups.Spearman correlation analysis was used to explore the correlation between clinical indicators and the occurrence of DPN in the elderly.Logistic regression was used to analyze the influencing factors for DPN in the elderly,and a nomogram was constructed.The receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of the model.Results The DM duration,DR and HbA1c were higher(P<0.05),while HDL-C was lower in the DPN group than in the T2DM group(P<0.05).Spearman correlation analysis showed that elderly DPN were positively correlated with DR,DM duration and HbA1c(r=0.456,0.565,0.580,P<0.05),and negatively correlated with HDL-C(r=-0.542,P<0.05).Logistic regression analysis showed that DR(OR 1.035,95%CI 1.032～1.040),DM duration(OR 1.070,95%CI 1.045～1.080),HbA1c(OR 1.235,95%CI 1.156～1.280)and HDL-C(OR 0.895,95%CI 0.877～0.950)were both influencing factors for elderly DPN.A nomogram prediction model for elderly DPN was constructed based on DR,DM duration,HbA1c and HDL-C.ROC curve analysis showed that the area under curve of this prediction model was 0.955,with a sensitivity of 92.50%,a specificity of 95.00%,and a cutoff value of 0.251.Conclusions The established predictive diagram model involves four variables,including DR,DM duration,HbA1c and HDL-C,which can assist the clinic to make an early assessment of DPN risk.

BACKGROUND:It has also been confirmed that ferroptosis is closely related to a variety of musculoskeletal diseases,such as rheumatoid arthritis,osteosarcoma,and osteoporosis.The pathophysiological mechanisms of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and osteoporosis.It will provide research ideas for the future elucidation of new mechanisms of osteoporosis and the development of new technologies and drugs for the treatment of osteoporosis. OBJECTIVE:To provide an overview of the current status of research on ferroptosis in osteoporosis,to provide a new direction for future research on the specific molecular mechanisms of osteoporosis,and to provide more effective and better options for osteoporosis treatment strategies. METHODS:The first author used the computer to search the literature published from 2000 to 2024 in CNKI,WanFang,VIP,and PubMed databases with search terms"ferroptosis,iron metabolism,osteoporosis,osteoblast,osteoclast,bone metabolism,signal pathway,musculoskeletal,review"in Chinese and English.A total of 68 articles were finally included according to the selection criteria. RESULTS AND CONCLUSION:(1)Ferroptosis is a new type of cell death discovered in recent years,which is usually accompanied by a large amount of iron accumulation and lipid peroxidation during cell death,and its occurrence is iron-dependent.This is distinctly different from several types of cell death that are currently being hotly studied(e.g.,cellular pyroptosis,necrotic apoptosis,cuproptosis,and autophagy).(2)Intracellular iron homeostasis is manifested as a balance between iron uptake,export,utilization,and storage.The body's iron regulatory system includes systemic and intracellular regulation.The main factor of systemic regulation is hepcidin produced by hepatic secretion,and cellular regulation depends on the iron regulatory protein/iron response element system.Of course,intracellular iron homeostasis can be controlled by other factors,such as hypoxia,cytokines,and hormones.(3)Lipid peroxidation causes oxidative damage to biological membranes(plasma membrane and internal organelle membranes),lipoproteins,and other lipid-containing molecules.Polyunsaturated fatty acid-containing phospholipids are important targets of lipid peroxidation.Free polyunsaturated fatty acid is an important substrate for lipid oxidation and can bind to the phospholipid bilayer,leading to over-oxidation and thus triggering lipid apoptosis.(4)Several studies have shown that osteoblasts are overloaded with iron in different ways,resulting in the accumulation of unstable ferrous iron and the generation of reactive oxygen species and lipid peroxides,causing ferroptosis of osteoblasts and ultimately a decrease in bone formation,affecting bone homeostasis and the development of osteoporosis.(5)Osteoclasts are large multinucleated cells formed by the fusion of mononuclear macrophage cell lines or bone marrow mesenchymal stem cells induced by nuclear factor-κB ligand receptor activator,and they have the function of bone resorption.Iron ions can promote osteoclast differentiation and bone resorption through the production of intracellular lipid reactive oxygen species,while iron chelators can inhibit osteoclast formation in vitro and thus affect the occurrence and development of osteoporosis.