BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400 μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400 μmol/L cobalt nanoparticles and 25 μmol/L deferiprone),the deferiprone group(25 μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P＜0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factor α,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factor α,interleukin-1β,and interleukin-6)significantly decreased(P＜0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P＜0.05),while deferiprone inhibited this effect(P＜0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.

Objective:To investigate the radiographic changes of calcification of transverse atlantal ligament by clinical case study and improve the understanding of it.Methods:A retrospective analysis was performed to identify the clinical cases of transverse atlantebral ligament calcification. Eleven cases in the orthopedic department of our hospital from January 2015 to December 2022 were identifiled.Results:In this study, a total of 11 patients with calcification of atlas transverse ligament, which showed crowned dens sign (CDSig). Five patients were males and 6 were females, with an average age of 79.9 years (70~89 years). The average follow-up time was 44.7 months (14~89 months), 7 cases had no significant change in calcification, and 4 patients had aggravated calcification. These 11 patients accounted for 28 clinical visits in total, with the primary reasons for consultation as follows: 7 visits were related to cerebrovascular diseases, 6 visits were due to respiratory diseases, 5 visits were for surgical conditions. None of the patients reported a history of "acute neck pain".Conclusion:When patients with CDSig are complicated by acute neck pain, crowned dens syndrome should be considered on the basis of exclusion of malignant diseases such as meningitis. Calcification of the transverse atlanto-vertebral ligament is closely related to age, and calcification develops slowly, and may become worse with age.

Objective:To investigate the safety of the tetravalent meningococcal conjugate vaccine (MPCV-ACYW) in combination with the inactivated poliomyelitis (IPV) vaccine and diphtheria-tetanus-acellular pertussis (DTaP) vaccine for infants aged 3-5 months and provide real-world evidence for the immunization strategy of vaccine combination.Methods:From June to October 2023, a total of 600 3-month-old infants were selected and divided into three groups: control group, mono-vaccination group and combined vaccination group. They were simultaneously or individually vaccinated with MPCV-ACYW, IPV and DTaP vaccines at 3, 4, and 5 months of age, respectively. The incidence rate of adverse reactions within 30 days after each dose was observed.Results:All 600 infants completed at least one vaccination and entered the safety data analysis. The age of the control group (100 infants), the mono-vaccination group (250 infants), and the combination group (250 infants) was (101.20±7.88), (102.26±7.94), and (102.35±7.76) days, respectively. The body lengths were (63.00±3.02), (62.55±3.06), and (63.14±4.02) cm, respectively. The body weights were (6.90±0.77), (6.86±0.94), and (6.99±0.95) kg, respectively. Boys accounted for 49%, 50.4%, and 52.4%, respectively, with no statistically significant differences (all P>0.05). The overall incidence rates of adverse reactions in the control group, mono-vaccination group, and combined vaccination group were 4.00%, 2.80%, and 3.20%, respectively, with systemic adverse reaction rates of 3.00%, 2.40%, and 2.00%. The incidence rates of local adverse reactions were 1.00%, 0.40%, and 1.20%, with no statistically significant differences (all P>0.05). Adverse reactions were mainly grade 1, with incidence rates of grade 1 adverse reactions of 3.00%, 2.00%, and 1.60% in the three groups, and incidence rates of grade 2 adverse reactions of 1.00%, 0.80%, and 1.60%, respectively. No grade 3 or 4 serious adverse reactions occurred, and the differences were not statistically significant (all P>0.05). The adverse reaction symptoms of the three groups were mainly systemic reactions, among which fever and diarrhea symptoms were reported in individual cases in each group, with no statistically significant differences in the incidence rate (all P>0.05). The symptoms of adverse reactions were mostly transient and self-relieved, all of which were cured. Conclusion:The combination of MPCV-ACYW and IPV or DTaP vaccines is safe for infants aged 3-5 months.

BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400 μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400 μmol/L cobalt nanoparticles and 25 μmol/L deferiprone),the deferiprone group(25 μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P＜0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factor α,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factor α,interleukin-1β,and interleukin-6)significantly decreased(P＜0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P＜0.05),while deferiprone inhibited this effect(P＜0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.

Objective:To investigate the safety of the tetravalent meningococcal conjugate vaccine (MPCV-ACYW) in combination with the inactivated poliomyelitis (IPV) vaccine and diphtheria-tetanus-acellular pertussis (DTaP) vaccine for infants aged 3-5 months and provide real-world evidence for the immunization strategy of vaccine combination.Methods:From June to October 2023, a total of 600 3-month-old infants were selected and divided into three groups: control group, mono-vaccination group and combined vaccination group. They were simultaneously or individually vaccinated with MPCV-ACYW, IPV and DTaP vaccines at 3, 4, and 5 months of age, respectively. The incidence rate of adverse reactions within 30 days after each dose was observed.Results:All 600 infants completed at least one vaccination and entered the safety data analysis. The age of the control group (100 infants), the mono-vaccination group (250 infants), and the combination group (250 infants) was (101.20±7.88), (102.26±7.94), and (102.35±7.76) days, respectively. The body lengths were (63.00±3.02), (62.55±3.06), and (63.14±4.02) cm, respectively. The body weights were (6.90±0.77), (6.86±0.94), and (6.99±0.95) kg, respectively. Boys accounted for 49%, 50.4%, and 52.4%, respectively, with no statistically significant differences (all P>0.05). The overall incidence rates of adverse reactions in the control group, mono-vaccination group, and combined vaccination group were 4.00%, 2.80%, and 3.20%, respectively, with systemic adverse reaction rates of 3.00%, 2.40%, and 2.00%. The incidence rates of local adverse reactions were 1.00%, 0.40%, and 1.20%, with no statistically significant differences (all P>0.05). Adverse reactions were mainly grade 1, with incidence rates of grade 1 adverse reactions of 3.00%, 2.00%, and 1.60% in the three groups, and incidence rates of grade 2 adverse reactions of 1.00%, 0.80%, and 1.60%, respectively. No grade 3 or 4 serious adverse reactions occurred, and the differences were not statistically significant (all P>0.05). The adverse reaction symptoms of the three groups were mainly systemic reactions, among which fever and diarrhea symptoms were reported in individual cases in each group, with no statistically significant differences in the incidence rate (all P>0.05). The symptoms of adverse reactions were mostly transient and self-relieved, all of which were cured. Conclusion:The combination of MPCV-ACYW and IPV or DTaP vaccines is safe for infants aged 3-5 months.

Objective:To investigate the radiographic changes of calcification of transverse atlantal ligament by clinical case study and improve the understanding of it.Methods:A retrospective analysis was performed to identify the clinical cases of transverse atlantebral ligament calcification. Eleven cases in the orthopedic department of our hospital from January 2015 to December 2022 were identifiled.Results:In this study, a total of 11 patients with calcification of atlas transverse ligament, which showed crowned dens sign (CDSig). Five patients were males and 6 were females, with an average age of 79.9 years (70~89 years). The average follow-up time was 44.7 months (14~89 months), 7 cases had no significant change in calcification, and 4 patients had aggravated calcification. These 11 patients accounted for 28 clinical visits in total, with the primary reasons for consultation as follows: 7 visits were related to cerebrovascular diseases, 6 visits were due to respiratory diseases, 5 visits were for surgical conditions. None of the patients reported a history of "acute neck pain".Conclusion:When patients with CDSig are complicated by acute neck pain, crowned dens syndrome should be considered on the basis of exclusion of malignant diseases such as meningitis. Calcification of the transverse atlanto-vertebral ligament is closely related to age, and calcification develops slowly, and may become worse with age.

The neuropathic damage of Parkinson disease(PD)is irreversible.In recent years,advances in PD re-search frontiers have found that decades before the typical motor symptoms of PD,some pathological changes already hap-pen.This interval prior to diagnosis,or the prodromal phase of PD,is an excellent window for neuroprotective therapy re-search,and this type of research may create a breakthrough in developing effective treatment for PD,reducing the inci-dence of PD,and delaying the progression of PD.This review on prodromal PD-related literature summarizes current clini-cal research design methods,and discusses the decision-making around clinical trial design with regard to study popula-tion,sample size,outcome indicators,safety,and subject diaries,aiming to provide a reference for the design of clinical trials of prodromal PD.

Objective:To identify the spatial clustering and its temporal trends among newly reported HIV/AIDS cases in Henan Province during 1995-2020, and to provide evidence for strategies on prevention and control of the disease.Methods:Information about newly reported HIV/AIDS cases in Henan between 1995 and 2020 were obtained from China Information System for Disease Control and Prevention and to describe their demographic characteristics, spatial autocorrelation and changing trends. This program was conducted at county level, using the ArcGIS 10.2.Results:A total of 96 528 HIV/AIDS cases with complete current address information in counties (districts) were newly reported during 1995-2020 in Henan, and the spatial autocorrelation analysis showed that Global Moran's I index was 0.249, Z G value of the Global Getis-Ord G coefficient was 6.472 (all P<0.001), indicating that there was a high clustered positive spatial autocorrelation of HIV/AIDS. The newly reported HIV/AIDS cases from 1995 to 2000, 2001 to 2005, 2006 to 2010, 2011 to 2015, and 2016 to 2020 in Henan Province all exhibited high values of global spatial clustering. Their Moran's I indices were 0.197, 0.103, 0.491, 0.411 and 0.383, respectively. The Z G values of the Global Getis-Ord G coefficient were 4.580, 3.386, 10.246, 8.378 and 8.093, respectively. All of global spatial correlation were statistically significant (all P<0.001). The results of local spatial autocorrelation analysis showed that newly reported HIV/AIDS cases in Henan Province had high-high clustering areas at each time stage mentioned above. The number of high-high clustering counties/districts gradually increased from 6 in 2001-2005 to 21 in 2016-2020, spreading from Zhumadian City and Zhoukou City in southeast Henan to Nanyang City in southwest Henan, Zhengzhou City and its surrounding counties/districts in central Henan. Conclusions:In Henan Province, an increasing trend of clusters appeared on HIV epidemic among newly reported HIV/AIDS cases from 1995 to 2020, and high-high clustering areas gradually expanded from Zhumadian City and Zhoukou City to Nanyang City, Zhengzhou City and its surrounding counties/districts, indicating that it is necessary to strengthen the AIDS prevention and control programs in these areas in Henan.

Objective To explore the trajectory and influencing factors of joint awareness after total knee arthroplasty.Methods With the method for convenience sampling,patients who met the standards for total knee arthroplasty from July 2021 to March 2022 were selected.General information,severity of osteoarthritis,anxiety and depression,and self-efficacy were investigated before surgery(T0).Joint awareness was investigated at 1 month(T1),3 months(T2),and 6 months(T3)after surgery,respectively.Latent growth curve model was used to describe the overall trend of joint awareness;latent class growth model was used to analyze latent subgroups;logistic regression analysis was used to determine the impact of related variables on the trajectory of joint awareness.Results The scores of joint awareness were(32.70±5.80),(47.67±4.67)and(61.53±7.81)respectively at T1 to T3,and joint awareness showed an increasing trend(P＜0.001).The trajectory of joint awareness was divided into 2 potential subgroups:the rapid growth group(61.83％)and the slow growth group(38.17％).Age,BMI,other chronic diseases or not,years of osteoarthritis,severity of osteoarthritis,anxiety,depression,and self-efficacy affected the trend of joint awareness(all P＜0.05).Conclusion Joint awareness showed a linear growth trend with the postoperative time,and there were 2 potential subgroups in the trajectory.Medical workers could develop corresponding interventions based on the influencing factors to improve patients'postoperative awareness of artificial joints.

ObjectiveTo compare the effects of different processing methods in ancient and modern times on the chemical components of Lilii Bulbus decoction， and to provide experimental support for the origin processing， decoction piece processing and clinical application of this herb. MethodUltra high performance liquid chromatography tandem quadrupole electrostatic field orbitrap high resolution mass spectrometry（UHPLC-Q-Orbitrap HRMS） was used for structural identification of the compounds using excimer ions， secondary MS and characteristic fragment ions， and referring to relevant literature and database information. Principal component analysis（PCA） and orthogonal partial least squares discriminant analysis（OPLS-DA） were used to screen the main differential components， the differential components were quantitatively studied by high performance liquid chromatography（HPLC）， in order to compare the types and contents of chemical components in the decoction of different processing products of Lilii Bulbus. ResultA total of 24 chemical components were identified from the decoction of different processed products of Lilii Bulbus， water extract and scalding liquid of fresh Lilii Bulbus， including 17 phenols， 5 saponins and 2 alkaloids. Compared with the fresh Lilii Bulbus decoction， the contents of regaloside A， p-coumaric acid， colchicine and other components in the decoction of dry Lilii Bulbus processed by scalding method decreased， the content of regaloside C in the decoction of dry Lilii Bulbus processed by steaming method decreased， and the contents of regaloside A and regaloside C in the decoction of fresh Lilii Bulbus processed by water immersion also decreased. Compared with the decoction of dry Lilii Bulbus processed by scalding method， the overall content of components in the fresh Lilii Bulbus decoction and the decoction of fresh Lilii Bulbus processed by water immersion was higher， the contents of components in the decoction of dry Lilii Bulbus processed by steaming method was higher， except for the slightly lower content of regaloside C. ConclusionDifferent processing processes have a certain effect on the types and contents of chemical components in Lilii Bulbus decoction. Scalding process is beneficial to the preservation of Lilii Bulbus， but can cause the loss of effective components. Compared with scalding method， steaming method can prevent browning of Lilii Bulbus and reduce the loss of its active ingredients. The processing method of removing foam after overnight immersion proposed by ZHANG Zhongjing may be more conducive to the treatment of Baihe disease， which can provide reference for the clinical rational application and mechanism research of different processed products of Lilii Bulbus.