BACKGROUND:In the repair of large bone defects,a variety of factors such as seed cell passaging can cause senescence of osteoblasts,leading to a reduction in osteogenic differentiation activity after implantation of tissue-engineered bone.In recent years,a novel mechanism involving primary cilia in cell senescence has been widely studied,but the primary cilia-related mechanism of"passage senescence-reduced osteogenic activity"is not fully understood.OBJECTIVE:To explore the possible mechanisms by which primary cilia regulate the senescence of MC3T3-E1 cells.METHODS:The osteoblast precursor cell lines MC3T3-E1 were passaged to 10th generation cells(early passage)and 40th generation cells(late passage).siRNA was used to silence IFT88 to inhibit primary cilia formation.The cells were than grouped into passage 10 group,passage 40 group,passage 10+siRNA IFT88 group,and passage 40+siRNA IFT88 group.RT-PCR and western blot assays were used to detect the expression of the aging marker P16(CDKN2A),the osteogenic activity markers bone morphogenetic protein 2 and alkaline phosphatase,and the Hedgehog pathway IHH expression.Alizarin red staining and primary cilia immunofluorescence staining were performed.Spearman correlation analysis was conducted to analyze primary cilia positive rate and IHH and bone morphogenetic protein 2 expression.RESULTS AND CONCLUSION:(1)The expression of CDKN2A(P16)in the passage 10 group was significantly higher than in the passage 40 group,but the difference disappeared after siRNA IFT88 intervention.(2)Meanwhile,the positive rate of primary cilia cells in the passage 10 group were higher than in the passage 40 group,while siRNA IFT88-significantly inhibited the expression of primary cilia in both passage 10 and passage 40 cells.(3)The transcriptional activity and protein expression of bone morphogenetic protein 2 and alkaline phosphatase in the passage 10 group were higher than those in the passage 40 group.After inhibiting the expression of primary cilia with siRNA,the above differences were reduced or disappeared.(4)The positive rate of primary cilia cells was correlated with IHH and bone morphogenetic protein 2 protein expression.To conclude,primary cilia mediate the replicative senescence of osteogenic MC3T3-E1 cells and regulate osteogenic differentiation ability.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:To describe the epidemiological characteristics and trends of lung cancer incidence in Qidong City, Jiangsu Province, China, between 1972 and 2021, and provide guidelines for prevention and control.Methods:Data on lung cancer with onset from January 1, 1972 to December 31, 2021 and coded as C33-C34 in the International Classification of Diseases (10th edition) were extracted from the tumor registry database of Qidong City. Population data of Qidong City for each year from 1972 to 2021 were extracted from the annual report of household registration of the Public Security Bureau of Qidong City. The crude incidence rate (CR), China age-standardized rate (ASRC), world age-standardized rate (ASRW), 35-64 years truncated rate, 0-74 years cumulative rate, and cumulative risk were calculated. Average annual percentage change (AAPC) was calculated by Joinpoint software for CR, ASRC, and ASRW. The age-period-cohort (APC) model was used to analyze the influence of age, period, and birth cohort on the changes in the incidence trend of lung cancer.Results:From 1972 to 2021, there were 26 996 patients of lung cancer in Qidong, accounting for 18.30% (26 996/147 519) of all cancer new cases. The CR of lung cancer was 48.13/10 5, the ASRC was 29.65/10 5, and the ASRW was 29.67/10 5. The truncated incidence of 35-64 years old was 42.64/10 5, the cumulative incidence rate between the ages between 0-74 years old was 3.71%, and the cumulative risk was 3.64%. There were 18 572 male patients, with the CR, ASRC, and ASRW being 67.15/10 5, 43.82/10 5, and 43.87/10 5, respectively. The number of female patients was 8 424, and the CR, ASRC, and the ASRW were 29.62/10 5, 17.63/10 5, and 17.55/10 5, respectively. Temporal analysis indicated significant upward trends in the ASRCs for both genders combined, males, and females, with AAPC values of 2.21%, 1.76%, and 2.98% (all P<0.001), respectively. Age-specific incidence rates increased with age, peaking at 275.34/10 5 in the 75+ years age group, with an increasing trend in all age groups and the greatest increase in the 75+ years age group, with an AAPC value of 3.53% ( P<0.001). The results of the APC model showed that the net drift value of lung cancer incidence was 2.06% (95% CI: 1.72%-2.41%), and the highest value of local drift was 3.93% (95% CI: 3.20%-4.68%) in the 80+ years old group. The risk of cancer increases with age in the age effect. The period effect of the incidence rate ratio (RR) value increased from 1.12 during 1997-2001 to 2.09 during 2017-2021. The cohort effect of the RR value for risk of incidence increased from 0.17 during 1892-1896 to 2.54 during 1987-1991. Conclusions:From 1972 to 2021, the incidence rate of lung cancer in Qidong City showed an upward trend. Age, period, and cohort are all major factors influencing the incidence of lung cancer. It is necessary to develop precise and comprehensive prevention and control strategies to curb this increasing trend of lung cancer incidence.

Fluorine is a common chemical element. Excessive intake of fluoride can lead to fluorosis. Fluoride easily passes through the blood-brain barrier and accumulates in different brain regions, causing pathological changes in brain tissue. It leads to adverse effects on neuronal metabolism, enzyme, protein function, neurotransmitters, and redox homeostasis, and subsequently neuronal damage and neurodegenerative diseases in humans and experimental animals. This paper reviewed the effects and important mechanisms of fluoride on neurological function and behavior, involving mitochondrial toxicity, oxidative stress, cell apoptosis and autophagy, and activation of pro-inflammatory factors. It provided a reference for further studying the mechanisms of brain damage induced by fluorosis.

Objective:To describe the epidemiological characteristics and trends of lung cancer incidence in Qidong City, Jiangsu Province, China, between 1972 and 2021, and provide guidelines for prevention and control.Methods:Data on lung cancer with onset from January 1, 1972 to December 31, 2021 and coded as C33-C34 in the International Classification of Diseases (10th edition) were extracted from the tumor registry database of Qidong City. Population data of Qidong City for each year from 1972 to 2021 were extracted from the annual report of household registration of the Public Security Bureau of Qidong City. The crude incidence rate (CR), China age-standardized rate (ASRC), world age-standardized rate (ASRW), 35-64 years truncated rate, 0-74 years cumulative rate, and cumulative risk were calculated. Average annual percentage change (AAPC) was calculated by Joinpoint software for CR, ASRC, and ASRW. The age-period-cohort (APC) model was used to analyze the influence of age, period, and birth cohort on the changes in the incidence trend of lung cancer.Results:From 1972 to 2021, there were 26 996 patients of lung cancer in Qidong, accounting for 18.30% (26 996/147 519) of all cancer new cases. The CR of lung cancer was 48.13/10 5, the ASRC was 29.65/10 5, and the ASRW was 29.67/10 5. The truncated incidence of 35-64 years old was 42.64/10 5, the cumulative incidence rate between the ages between 0-74 years old was 3.71%, and the cumulative risk was 3.64%. There were 18 572 male patients, with the CR, ASRC, and ASRW being 67.15/10 5, 43.82/10 5, and 43.87/10 5, respectively. The number of female patients was 8 424, and the CR, ASRC, and the ASRW were 29.62/10 5, 17.63/10 5, and 17.55/10 5, respectively. Temporal analysis indicated significant upward trends in the ASRCs for both genders combined, males, and females, with AAPC values of 2.21%, 1.76%, and 2.98% (all P<0.001), respectively. Age-specific incidence rates increased with age, peaking at 275.34/10 5 in the 75+ years age group, with an increasing trend in all age groups and the greatest increase in the 75+ years age group, with an AAPC value of 3.53% ( P<0.001). The results of the APC model showed that the net drift value of lung cancer incidence was 2.06% (95% CI: 1.72%-2.41%), and the highest value of local drift was 3.93% (95% CI: 3.20%-4.68%) in the 80+ years old group. The risk of cancer increases with age in the age effect. The period effect of the incidence rate ratio (RR) value increased from 1.12 during 1997-2001 to 2.09 during 2017-2021. The cohort effect of the RR value for risk of incidence increased from 0.17 during 1892-1896 to 2.54 during 1987-1991. Conclusions:From 1972 to 2021, the incidence rate of lung cancer in Qidong City showed an upward trend. Age, period, and cohort are all major factors influencing the incidence of lung cancer. It is necessary to develop precise and comprehensive prevention and control strategies to curb this increasing trend of lung cancer incidence.

OBJECTIVE To investigate the prevalence of plasma vitamin B1 deficiency in patients with sepsis and analyze the relationship between plasma vitamin B1 levels and lactic acidosis.METHODS A total of 40 patients with sepsis and 42 patients with sepsis shock admitted to the intensive care unit(ICU)of General Hospital of Ningxia Medical University from Nov.2020 to Nov.2022 were selected as the study objects.Volunteers matched by age,gender and body mass index(BMI)were selected as the healthy group.Data on gender,age,BMI,under-lying diseases,sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluation(APACHE)Ⅱ score,infection site,duration of mechanical ventilation and ICU length of stay were collected.La-boratory tests including blood routine,electrolytes,blood lactate(Lac),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),blood urea nitrogen(BUN)and serum creatinine(Scr)were performed in both groups.Plasma samples from both disease group and the healthy group were collected.High-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to measure plasma thiamine(vitamin B1)levels in the disease group on the first,third and fifth days,respectively,as well as in the healthy group.RESULTS On the first day of admission,both the sepsis group and the septic shock group exhibited vitamin B1 de-ficiency.Specifically,6 cases of vitamin B1 deficiency were observed in the patients with sepsis,while 8 cases of vitamin B1 deficiency were noted in the patients with septic shock(P=0.640).By the third and fifth days,the proportions of vitamin B1 deficiency in the sepsis group were 22.50％and 42.50％,respectively,whereas in the septic shock group,these proportions were high at 26.19％and 54.76％,with a statistically significant difference(P＜0.05).On the fifth day,in the normal liver function group,vitamin B1 levels showed a negative correlation with lactate(r=-0.590,P=0.005),whereas in the abnormal liver function group,vitamin B1 levels were pos-itively correlated with lactate(r=0.678,P=0.017).The patients in the septic shock group had low K+and ALB levels[(2.60±0.42)mmol/L and(24.56±5.78)g/L,respectively]compared to those in the sepsis group(P＜0.05).CONCLUSIONS Plasma vitamin B1 deficiency is prevalent among patients with sepsis.Changes in plasma vitamin B1 levels are closely associated with blood lactate levels in these patients.

OBJECTIVE To investigate the prevalence of plasma vitamin B1 deficiency in patients with sepsis and analyze the relationship between plasma vitamin B1 levels and lactic acidosis.METHODS A total of 40 patients with sepsis and 42 patients with sepsis shock admitted to the intensive care unit(ICU)of General Hospital of Ningxia Medical University from Nov.2020 to Nov.2022 were selected as the study objects.Volunteers matched by age,gender and body mass index(BMI)were selected as the healthy group.Data on gender,age,BMI,under-lying diseases,sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluation(APACHE)Ⅱ score,infection site,duration of mechanical ventilation and ICU length of stay were collected.La-boratory tests including blood routine,electrolytes,blood lactate(Lac),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),blood urea nitrogen(BUN)and serum creatinine(Scr)were performed in both groups.Plasma samples from both disease group and the healthy group were collected.High-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to measure plasma thiamine(vitamin B1)levels in the disease group on the first,third and fifth days,respectively,as well as in the healthy group.RESULTS On the first day of admission,both the sepsis group and the septic shock group exhibited vitamin B1 de-ficiency.Specifically,6 cases of vitamin B1 deficiency were observed in the patients with sepsis,while 8 cases of vitamin B1 deficiency were noted in the patients with septic shock(P=0.640).By the third and fifth days,the proportions of vitamin B1 deficiency in the sepsis group were 22.50％and 42.50％,respectively,whereas in the septic shock group,these proportions were high at 26.19％and 54.76％,with a statistically significant difference(P＜0.05).On the fifth day,in the normal liver function group,vitamin B1 levels showed a negative correlation with lactate(r=-0.590,P=0.005),whereas in the abnormal liver function group,vitamin B1 levels were pos-itively correlated with lactate(r=0.678,P=0.017).The patients in the septic shock group had low K+and ALB levels[(2.60±0.42)mmol/L and(24.56±5.78)g/L,respectively]compared to those in the sepsis group(P＜0.05).CONCLUSIONS Plasma vitamin B1 deficiency is prevalent among patients with sepsis.Changes in plasma vitamin B1 levels are closely associated with blood lactate levels in these patients.

BACKGROUND:In the repair of large bone defects,a variety of factors such as seed cell passaging can cause senescence of osteoblasts,leading to a reduction in osteogenic differentiation activity after implantation of tissue-engineered bone.In recent years,a novel mechanism involving primary cilia in cell senescence has been widely studied,but the primary cilia-related mechanism of"passage senescence-reduced osteogenic activity"is not fully understood.OBJECTIVE:To explore the possible mechanisms by which primary cilia regulate the senescence of MC3T3-E1 cells.METHODS:The osteoblast precursor cell lines MC3T3-E1 were passaged to 10th generation cells(early passage)and 40th generation cells(late passage).siRNA was used to silence IFT88 to inhibit primary cilia formation.The cells were than grouped into passage 10 group,passage 40 group,passage 10+siRNA IFT88 group,and passage 40+siRNA IFT88 group.RT-PCR and western blot assays were used to detect the expression of the aging marker P16(CDKN2A),the osteogenic activity markers bone morphogenetic protein 2 and alkaline phosphatase,and the Hedgehog pathway IHH expression.Alizarin red staining and primary cilia immunofluorescence staining were performed.Spearman correlation analysis was conducted to analyze primary cilia positive rate and IHH and bone morphogenetic protein 2 expression.RESULTS AND CONCLUSION:(1)The expression of CDKN2A(P16)in the passage 10 group was significantly higher than in the passage 40 group,but the difference disappeared after siRNA IFT88 intervention.(2)Meanwhile,the positive rate of primary cilia cells in the passage 10 group were higher than in the passage 40 group,while siRNA IFT88-significantly inhibited the expression of primary cilia in both passage 10 and passage 40 cells.(3)The transcriptional activity and protein expression of bone morphogenetic protein 2 and alkaline phosphatase in the passage 10 group were higher than those in the passage 40 group.After inhibiting the expression of primary cilia with siRNA,the above differences were reduced or disappeared.(4)The positive rate of primary cilia cells was correlated with IHH and bone morphogenetic protein 2 protein expression.To conclude,primary cilia mediate the replicative senescence of osteogenic MC3T3-E1 cells and regulate osteogenic differentiation ability.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objectives:Quantitative flow ratio(QFR)is a coronary angiography-derived functional test without the need of guidewire use.Fractional flow reserve(FFR)is used as the reference standard to verify the diagnostic value of QFR in patients with non-ST-segment elevation acute coronary syndrome(NSTE-ACS)with coronary critical lesion(40%-70%stenosis)and functional stenosis. Methods:This retrospective analysis included patients with NSTE-ACS who were admitted to Fuwai Central China Cardiovascular Hospital from June 1,2018 to February 1,2023 and underwent coronary FFR examination.QFR values of target vessels were analyzed offline by AngioPlus(Shanghai Pulsation Medical Imaging Technology Co.,LTD.),the second-generation QFR detector,and anatomical parameters of the diseased vessels were recorded as follows:minimal luminal diameter(MLD),percent diameter stenosis(DS%),minimal luminal area(MLA),percent area stenosis(AS%).Functional coronary artery stenosis is defined as FFR≤0.80. Results:Using FFR as the gold standard,the AUC values of contrast-flow QFR(cQFR)and fixed-flow QFR(fQFR)for identifying functional coronary artery stenosis in NSTE-ACS patients were 0.829(95%CI:0.773-0.885,P<0.001)and 0.821(95%CI:0.766-0.875,P<0.001),respectively.The diagnostic accuracy,sensitivity and specificity of cQFR and fQFR were 81.30%,56.00%,98.63%and 76.83%,59.00%,99.04%,respectively.DeLong test showed that diagnostic performance of cQFR was significantly better than fQFR in diagnosing functional stenosis of coronary critical lesions in patients with NSTE-ACS. Conclusions:With FFR as the gold standard,QFR(especially cQFR)has certain diagnostic value in patients with NSTE-ACS with functional stenosis of coronary critical lesions.