Osteoarthritis(OA),a common age-related chronic disease,is characterized by degenerative changes in the joints and surrounding tissues.Traditionally,research on OA has primarily focused on the pathological changes in articular cartilage and its repair.However,with the advancements in animal disease modeling in recent years,especially the widespread use of spatiotemporally specific transgenic mouse models,scholars have gradually come to realize that the subchondral bone also plays an important role in the occurrence and development of OA.That is,the pathological changes in articular cartilage and bone mutually affect and promote each other,jointly driving the progression of OA,involving such pathological processes as vascular invasion,ectopic calcification,nerve growth,and the occurrence of pain.Given the complexity of cartilage-bone pathological relationship,it is difficult to conduct in-depth research on subchondral bone pathology using clinical human samples,or to simulate the pathological processes of OA through in vitro cell experiments.Therefore,animal models play an irreplaceable role in investigating the pathological mechanisms of OA and developing clinical drugs.This review,in addition to providing an overview of OA animal models,synthesizes the latest progress in animal experimental research on OA,highlighting the active role of the cartilage-bone pathological relationship in OA progression.These new findings provide references for future in-depth investigations and also provide a theoretical basis for developing fundamental strategies for OA prevention and treatment.

Osteoporosis and cardiovascular calcification,two major age-related chronic diseases that China is confronting today,pose serious threats to public health.Previous studies have reported overlapping connections in the pathological processes and molecular mechanisms of these two diseases,particularly concerning inflammation,oxidative stress,and dysregulation of mineral metabolism,and that these two diseases tend to share common pathogenic factors.However,research exploring the comorbidity mechanisms of the two diseases remains limited in both depth and scope,largely due to the lack of widely accepted comorbidity animal models.Herein,we analyzed the latest research findings on the comorbidity mechanisms of vascular calcification and osteoporosis,focusing on summarizing the animal disease models currently in extensive use and the relevant evaluation criteria.We aim to provide new references for comorbidity research models and offer scientific evidence for future studies on pathological mechanisms and the development of new therapeutic strategies.

Objective:To investigate relationship between serum immunoglobulin(Ig),forkhead box protein P3(Foxp3)and therapeutic effect of nivolumab in patients with advanced non-small cell lung cancer(NSCLC).Methods:A total of 180 advanced NSCLC patients admitted to Hengshui People's Hospital between January 2020 and January 2024 were selected as NSCLC group,and 180 healthy individuals who underwent physical examinations during same period were selected as healthy group.Serum IgA,IgM,IgG and Foxp3 levels were measured,and differences in serum IgA,IgM,IgG and Foxp3 levels between two groups were compared,as well as their differences of levels in different clinical characteristics of advanced NSCLC patients.Advanced NSCLC patients were treated with nivolumab on basis of paclitaxel and carboplatin chemotherapy,and divided into treatment effective group(n=82)and treatment ineffective group(n=98)based on efficacy.Differences of serum IgG and Foxp3 levels between two groups were compared,and efficacy of serum IgG and Foxp3 in predicting therapeutic effect of nivolumab in advanced NSCLC patients was analyzed.Results:Serum IgG and Foxp3 levels in NSCLC group were higher than healthy group(P<0.05),and there was no statistically significant difference in serum IgA and IgM levels between two groups(P>0.05).Serum IgG and Foxp3 levels in TNM stage Ⅳ and poorly differentiated NSCLC patients were higher than stage Ⅲ NSCLC patients(P<0.05).TNM stage Ⅳ,proportion of low differentiation,and serum IgG and Foxp3 levels in ineffective group were higher than effective group(P<0.05).Logistic regression analysis showed that differentiation level,high IgG and high Foxp3 levels were risk factors for ineffective treatment with nivolumab in advanced NSCLC patients(P<0.05).Predictive efficacy of combination of serum IgG and Foxp3 in treatment of advanced NSCLC patients with nivolumab was superior to any single therapy,with an AUC of 0.978,sensitivity of 96.75%,and specificity of 92.13%.Conclusion:Elevated serum IgG and Foxp3 levels in patients with advanced NSCLC are risk factors for nivolumab treatment failure,and can be used as a reference index to predict therapeutic effect of nivolumab.

Objective To explore the clinical efficacy of modified anteromedia approach with superior extensor retinaculars and traditional anteromedia combined with posterolateral approach in the treatment of Rüedi-Allg?wer type Ⅲ Pilon fractures.Methods In this study selected 56 patients with Rüedi-Allg?wer type Ⅲ Pilon fractures treated in our hospital from January 2020 to January 2022,all of whom met the inclusion and exclusion criteria,27 in the experimental group and 29 in the control group.Both groups underwent open reduction and internal fixation of Pilon fractures.The experimental group used a modified anteromedial approach to preserve the supraspinatus,while the control group used a traditional anteromedial combined with posterolateral approach to cut off the supraspinatus.The general clinical data,operation time,intraoperative blood loss,postoperative drainage volume,fracture reduction quality,early pain VAS score,complications and ankle function evaluation of the experimental group and the control group were compared in detail,and the early clinical efficacy of the two surgical methods was analyzed and compared.Results There were no significant differences in age,gender,body mass index(BMI),complications,injury mechanism and the time from admission to operation between the experimental group and the control group(P>0.05).Experimental group:operation time(115.92±12.23)min,intraoperative blood loss(129.25±16.15)mL,postoperative drainage volume(82.44±25.57)mL,fracture healing time(17.89±2.39)w;Control group:operation time(172.75±15.09)min,intraoperative blood loss(177.24±14.36)mL,postoperative drainage volume(115.06±21.95)mL,fracture healing time(19.93±3.75)w.The operative time and fracture healing time of the experimental group were less than those of the control group(P<0.05),and the intraoperative blood loss and postoperative drainage volume of the experimental group were less than those of the control group,the difference was statistically significant(P<0.05).The Buewell-Charnley fracture reduction radio-logical evaluation criteria were used to evaluate the fracture reduction,and the rate of good reduction was 96.29%in the experimental group and 93.10%in the control group.There was no statistical significance in the anatomical reduction between the two groups(P>0.05).Visual analog scale(VAS)was used to evaluate postoperative pain,and pain VAS scores of the experimental group were lower than those of the control group at 3 days,1 week and 4 weeks after surgery(P<0.05).Both groups were followed up for at least 12 months after surgery,and the incidence of postoperative complications in the experimental group was lower than that in the control group(P<0.05).The AOFAS score of the experimental group was higher than that of the control group at 3 months,6 months and 12 months after surgery(P<0.05).Conclusion Improvement on the medial approach retains the superior extensor retinaculum,relative to the combined surgical approach to cut off the superior extensor retinacu-lum treatment Rüedi-Allg?wer Ⅲ Pilon fractures,with shorter operation time,less intraoperative blood loss,less postoperative complications and other advantages.The functional recovery of the ankle joint in the modified antero-medial approach preserving the superior extensor retinaculum was better than that in the combined approach cutting the superior extensor retinaculum.

Objective:To investigate relationship between serum immunoglobulin(Ig),forkhead box protein P3(Foxp3)and therapeutic effect of nivolumab in patients with advanced non-small cell lung cancer(NSCLC).Methods:A total of 180 advanced NSCLC patients admitted to Hengshui People's Hospital between January 2020 and January 2024 were selected as NSCLC group,and 180 healthy individuals who underwent physical examinations during same period were selected as healthy group.Serum IgA,IgM,IgG and Foxp3 levels were measured,and differences in serum IgA,IgM,IgG and Foxp3 levels between two groups were compared,as well as their differences of levels in different clinical characteristics of advanced NSCLC patients.Advanced NSCLC patients were treated with nivolumab on basis of paclitaxel and carboplatin chemotherapy,and divided into treatment effective group(n=82)and treatment ineffective group(n=98)based on efficacy.Differences of serum IgG and Foxp3 levels between two groups were compared,and efficacy of serum IgG and Foxp3 in predicting therapeutic effect of nivolumab in advanced NSCLC patients was analyzed.Results:Serum IgG and Foxp3 levels in NSCLC group were higher than healthy group(P<0.05),and there was no statistically significant difference in serum IgA and IgM levels between two groups(P>0.05).Serum IgG and Foxp3 levels in TNM stage Ⅳ and poorly differentiated NSCLC patients were higher than stage Ⅲ NSCLC patients(P<0.05).TNM stage Ⅳ,proportion of low differentiation,and serum IgG and Foxp3 levels in ineffective group were higher than effective group(P<0.05).Logistic regression analysis showed that differentiation level,high IgG and high Foxp3 levels were risk factors for ineffective treatment with nivolumab in advanced NSCLC patients(P<0.05).Predictive efficacy of combination of serum IgG and Foxp3 in treatment of advanced NSCLC patients with nivolumab was superior to any single therapy,with an AUC of 0.978,sensitivity of 96.75%,and specificity of 92.13%.Conclusion:Elevated serum IgG and Foxp3 levels in patients with advanced NSCLC are risk factors for nivolumab treatment failure,and can be used as a reference index to predict therapeutic effect of nivolumab.

Objective To explore the clinical efficacy of modified anteromedia approach with superior extensor retinaculars and traditional anteromedia combined with posterolateral approach in the treatment of Rüedi-Allg?wer type Ⅲ Pilon fractures.Methods In this study selected 56 patients with Rüedi-Allg?wer type Ⅲ Pilon fractures treated in our hospital from January 2020 to January 2022,all of whom met the inclusion and exclusion criteria,27 in the experimental group and 29 in the control group.Both groups underwent open reduction and internal fixation of Pilon fractures.The experimental group used a modified anteromedial approach to preserve the supraspinatus,while the control group used a traditional anteromedial combined with posterolateral approach to cut off the supraspinatus.The general clinical data,operation time,intraoperative blood loss,postoperative drainage volume,fracture reduction quality,early pain VAS score,complications and ankle function evaluation of the experimental group and the control group were compared in detail,and the early clinical efficacy of the two surgical methods was analyzed and compared.Results There were no significant differences in age,gender,body mass index(BMI),complications,injury mechanism and the time from admission to operation between the experimental group and the control group(P>0.05).Experimental group:operation time(115.92±12.23)min,intraoperative blood loss(129.25±16.15)mL,postoperative drainage volume(82.44±25.57)mL,fracture healing time(17.89±2.39)w;Control group:operation time(172.75±15.09)min,intraoperative blood loss(177.24±14.36)mL,postoperative drainage volume(115.06±21.95)mL,fracture healing time(19.93±3.75)w.The operative time and fracture healing time of the experimental group were less than those of the control group(P<0.05),and the intraoperative blood loss and postoperative drainage volume of the experimental group were less than those of the control group,the difference was statistically significant(P<0.05).The Buewell-Charnley fracture reduction radio-logical evaluation criteria were used to evaluate the fracture reduction,and the rate of good reduction was 96.29%in the experimental group and 93.10%in the control group.There was no statistical significance in the anatomical reduction between the two groups(P>0.05).Visual analog scale(VAS)was used to evaluate postoperative pain,and pain VAS scores of the experimental group were lower than those of the control group at 3 days,1 week and 4 weeks after surgery(P<0.05).Both groups were followed up for at least 12 months after surgery,and the incidence of postoperative complications in the experimental group was lower than that in the control group(P<0.05).The AOFAS score of the experimental group was higher than that of the control group at 3 months,6 months and 12 months after surgery(P<0.05).Conclusion Improvement on the medial approach retains the superior extensor retinaculum,relative to the combined surgical approach to cut off the superior extensor retinacu-lum treatment Rüedi-Allg?wer Ⅲ Pilon fractures,with shorter operation time,less intraoperative blood loss,less postoperative complications and other advantages.The functional recovery of the ankle joint in the modified antero-medial approach preserving the superior extensor retinaculum was better than that in the combined approach cutting the superior extensor retinaculum.

The polyfoliate perforator flap is a new type of flap that was developed on the basis of the traditional polyfoliate myocutaneous flap, polyfoliate fascial flap and perforator flap. It overturns the traditional idea that the deep fascial vascular network is the fundamental for a survival of the flap, and enables the flaps to achieve the best profile and function of the recipient areas with minimal damage to the donor area. In order to improve the understanding of the polyfoliate perforator flap and further standardise its clinical application, this paper forms a consensus on the definition, classification, indications, operative points and precautions of the polyfoliate perforator flap, so as to provide references in diagnosis and treatment process and practical application for the surgeons.

ObjectiveTo understand the characteristics of PM_2.5 pollution in the air of Pearl River Delta city in Guangdong Province under the COVID-19 epidemic and the health risks of inhaling elements in PM_2.5. MethodsIn 2022， 10 PM_2.5 monitoring points were set up in 10 districts in Guangzhou， Shenzhen， Foshan and Zhuhai， and air samples were collected for 7 consecutive days every month to analyze the concentration of PM_2.5 and the 12 elements in PM_2.5. The classic "four-step" method was used to evaluate the carcinogenic risk and chronic non-carcinogenic risk of the elements in air PM_2.5 on health. The age-sensitive characteristics of metal elements were combined in the carcinogenic risk assessment， and age-sensitive factors were introduced to analyze the impact of air pollution on population health. ResultsA total of818 samples were collected. and the average annual PM_2.5 concentration in the four cities of the Pearl River Delta was 30.17 （1.00-166.00， s=21.06） μg·m^-3， which was lower than the concentration limit of the secondary standard of the Ambient Air Quality Standard （GB 3095-2012）. The difference of PM_2.5 concentration in the four cities was statistically significant. The PM_2.5 concentrations in Zhuhai and Shenzhen， which were located near the sea， were lower than those in Guangzhou and Foshan. The monthly mean concentration of PM_2.5 in the four cities was the lowest at 13.70 （4.00-34.00， s=5.93） μg·m^-3 in July and the highest at 57.73 （14.00-146.00， s=27.96） μg·m^-3 in January， showing a low concentration from May to October and a high concentration from November to April of the following year. The average daily PM_2.5 concentration exceeded the secondary standard for 29 days， mainly distributed in January and November. The average annual mass concentration of elements in PM_2.5 in the four cities was Al>Mn>Pb>As>Ni>Cr>Se>Sb>Cd>Tl>Be>Hg. AS and Mn have chronic non-carcinogenic risk in population， while Cr， AS， Cd， Be and Ni have carcinogenic risk in population. ConclusionThe PM_2.5 pollution levels of the four cities in the Pearl River Delta are low and variable. Coastal cities are lower than non-coastal cities， which shows the characteristics of first decreasing and then increasing throughout the year. The order of mass concentration of metal elements of PM_2.5 in four cities is basically the same except Be and Ni. As and Mn in PM_2.5 show a certain degree of chronic non-carcinogenic risk， and As， Cr， Cd， Ni and Be have a certain degree of carcinogenic risk. The four cities need to take effective intervention measures to continue to strengthen the pollution control and health protection of Cr， As， Cd and Mn in the air， and control the health burden caused by air pollution.

The polyfoliate perforator flap is a new type of flap that was developed on the basis of the traditional polyfoliate myocutaneous flap, polyfoliate fascial flap and perforator flap. It overturns the traditional idea that the deep fascial vascular network is the fundamental for a survival of the flap, and enables the flaps to achieve the best profile and function of the recipient areas with minimal damage to the donor area. In order to improve the understanding of the polyfoliate perforator flap and further standardise its clinical application, this paper forms a consensus on the definition, classification, indications, operative points and precautions of the polyfoliate perforator flap, so as to provide references in diagnosis and treatment process and practical application for the surgeons.

Objective:To explore the relationship between microsatellite instability (MSI) and Ki-67 expression level and the clinicopathological features of colorectal cancer, and investigate their impact for prognosis, so as to provide reference for prognostic judgment of colorectal cancer.Methods:The data of 183 patients who underwent radical colorectal cancer surgery and were diagnosed pathologically in the Department of General Surgery, the First Affiliated Hospital of Xinxiang Medical University from January 2017 to December 2019 were retrospectively analysed, including 101 males (55.2%)and 82 females(44.8%), ranged from 20 to 86 years and the mean age was(60.27±13.13)years. According to the results of mismatch repair protein immunohistochemical staining, the patients were divided into MSI-H group ( n=32) and MSI-L/MSS group ( n=151). According to the results of Ki-67 antigen immunohistochemical staining, the patients were divided into low Ki-67 expression group (<82.5%, n=136) and high Ki-67 expression group (≥82.5%, n=47) , among which 62 cases (78.5%) with low Ki-67 expression and 17 cases (21.5%) with high Ki-67 expression were in patients with Ⅲ+ Ⅳ stage colorectal cancer. The data of clinicopathological features, disease-free survival, and overall survival were collected and analyzed. The cotegorical variables were presented as n(%), and the comparisons between groups were performed using Chi-square test or Fisher′s exact test. The multivariate Logistic regression model was used to estimate the correlation between microsatellite instability and Ki-67 expression level and clinicopathologic characteristics of colorectal cancer. Kaplan-Meier survival curve and COX proportional hazards regression model were used to analyze the correlation between microsatellite instability and Ki-67 expression level and disease-free survival and overall survival. Results:Single factor analysis showed that the differences in gender ( χ2=4.37, P=0.037), tumor site ( χ2=26.40, P<0.001), tumor maximum diameter ( χ2=11.12, P=0.001) and nerve invasion ( χ2=5.53, P=0.019) between MSI-H group and MSI-L/MSS group were statistically significant. Multivariate Logistic regression model analysis showed that only gender ( OR=3.013, 95% CI: 1.183-7.672, P=0.021), tumor location ( OR=0.167, 95% CI: 0.067-0.419, P<0.001) and nerve invasion ( OR=0.202, 95% CI: 0.042-0.968, P=0.045) were independently correlative factors for MSI status. In Ⅲ+ Ⅳ stage colorectal cancers, the difference in tumor site between low Ki-67 expression group and high Ki-67 expression group was statistically significant( χ2=3.91, P=0.048). Multivariate Cox proportional hazards regression model analysis revealed that high Ki-67 expression ( HR=0.301, 95% CI: 0.118-0.768, P=0.012; HR=0.275, 95% CI: 0.083-0.912, P=0.035) and MSI-H ( HR=0.072, 95% CI: 0.010-0.525, P=0.009; HR=0.122, 95% CI: 0.017-0.900, P=0.039) were independently protective factors for disease-free survival and overall survival. Conclusions:MSI-H colorectal cancer is common in males, right-sided colonic cancers and non-neuroinvasive patients. In stage Ⅲ+ Ⅳ colorectal cancer, the expression level of Ki-67 in right-sided colonic cancer was lower than in left-sided colorectal cancer. Patients with MSI-H and high Ki-67 expressive colorectal cancer had longer disease-free survival, longer overall survival and better prognosis.