Osteoporotic fractures are characterized by reduced bone mass and microstructural abnormalities, leading to differences in the healing process compared to traumatic fractures. The fracture healing process is generally divided into the inflammatory phase, the repair phase and the remodeling phase. In patients with osteoporotic fractures, due to factors such as decreased bone density, reduced bone quality and aging, there are partial alterations in inflammatory cells and osteoimmunity associated with those three healing phases, ultimately affecting fracture healing. This article focuses on the differences in fracture healing between non-osteoporotic fractures and osteoporotic fractures, reviewing relevant research literature and consensus. It analyzes and discusses changes in bone marrow mesenchymal stem cells and bone metabolism during osteoporosis, the effects of inflammatory aging, underlying diseases, and anti-osteoporosis medications on fracture healing, as well as the changes observed after pharmacological intervention. The aim is to emphasize personalized treatment approaches that account for individual and bone-specific factors in managing osteoporotic fractures, striving to promote better fracture healing outcomes and improving patients' quality of life.

Objective:To search, evaluate, and synthesize the best evidence for the management of diabetes in patients after heart transplantation, in order to provide reference for blood glucose management in subsequent patients within transplant teams.Methods:Following the "6S" model, a systematic search was conducted for guidelines, expert consensus, systematic reviews, and primary studies on the management and prevention of diabetes mellitus after heart transplantation. The search period was from database inception to May 22, 2024. The articles were assessed for quality and evidence grading using the Joanna Briggs Institute Evidence-Based Health Care Center's quality appraisal standards and evidence grading and recommendation grading system.Results:A total of 11 articles were included, consisting of three guidelines, six expert consensus papers, and two systematic reviews. These studies covered six key areas: early risk factor assessment, expansion of post transplantation diabetes mellitus screening trials, management of modifiable risk factors, lifestyle changes, implementation of personalized blood sugar reduction plans, and microvascular complication management. A total of 33 relevant pieces of evidence were summarized.Conclusions:The transplant team should formulate personalized blood glucose management plans based on clinical contexts, and heart transplant recipients should also actively engage in blood glucose monitoring and management to improve prognosis.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Traditional Chinese Medicine(TCM)emphasizes syndrome differentiation and treatment,characterized by"maintaining the prescription if effective"and"changing the prescription if ineffective".Traditional randomized controlled trials(RCTs)are inadequate for evaluating the efficacy of dynamic treatment adjustments.The Sequential Multiple Assignment Randomized Trial(SMART)is an emerging adaptive research design that incorporates randomization at multiple stages,allowing for adjustments in subsequent interventions based on treatment responses.This approach is suitable for evaluating dynamic treatment regimens while retaining the low bias risk of traditional RCTs,making it highly promising for clinical research in TCM.This paper summarizes recent methodological advancements in SMART design,including different sample size estimation and statistical analysis methods for primary effect objectives,embedded adaptive intervention objectives,and optimization objectives,along with providing corresponding operational software.Additionally,it offers considerations for applying SMART design in TCM research,such as the selection of disease types,interventions,decision points,tailoring variables,sample size calculation,statistical methods,the importance of pilot trials,ethical considerations,and limitations.The aim is to promote the exploration and practice of this method in the field of TCM,thereby contributing to the generation of high-quality evidence-based evidence for TCM.

Objective:To investigate the molecular mechanisms by which HMGB1 in lung cancer cells affects the function of lung cancer cells themselves and immune cells through the NF-κB pathway.Methods:Western blot detected HMGB1 expressions in Lewis lung cancer(LLC)cells,Raw264.7 cells,and mouse spleen cells,while tumor cell lysates(TCL)with low HMGB1 was pre-pared by inhibiting HMGB1 expression in lung cancer cells with glycyrrhetinic acid(GA);the effects of endogenous HMGB1 inhibi-tion or TCL with low HMGB1 on apoptosis and proliferation of lung cancer cells were detected by flow cytometry and CCK-8;TCL with normal HMGB1 or TCL with low HMGB1 was prepared by freeze-thawing;Raw264.7 cells and mouse splenocytes were treated with them for 48 h.Apoptosis and CD69 expression were detected by flow cytometry,and secretion of cytokines IL-2,IL-4,IL-6,TNF-α and TNF-β were detected by ELISA;Western blot detected lung cancer cells or immune cells.Western blot was performed to detect the protein expression of key signaling molecules of the NF-κB signaling pathway in lung cancer cells or immune cells.Results:HMGB1 was expressed in LLC cells,Raw264.7 cells,and mouse spleen cells,among which LLC cells had the highest expression of HMGB1,and 30 μg/ml GA had the best inhibitory effect on HMGB1 expression in LLC cells.Endogenous HMGB1 in LLC cells could promote cell proliferation.Exogenous HMGB1 in TCL induced apoptosis in lung cancer cells and inhibited immune cell activation and prolifera-tion.Inhibition of endogenous HMGB1 in lung cancer cells leaded to activation of the apoptosis-inducing factor CASP9 in the NF-κB signaling pathway,which was inhibited in lung cancer cells or immune cells after the action of TCL with low HMGB1.Conclusion:Tumor cell HMGB1 has a dual role in lung carcinogenesis,promoting the proliferation of lung cancer cells while suppressing the func-tion of immune cells,which in turn causes lung carcinogenesis,a process associated with the activation of the NF-κB signaling path-way in different cells.

Objective:To investigate the current status of referral for critically ill pregnant women in Beijing and Chongqing,provide improvement strategies for the management of referral for critically ill pregnant women.Meth-ods:From May 2022 to June 2024,a self-made questionnaire was used to survey medical staff at different levels of midwifery institutions in Beijing and Chongqing through the internet.The survey targets 18 midwifery institutions in Haidian District and Changping District of Beijing,as well as 50 midwifery institutions in 25 districts and counties of Chongqing.Collect and analyze basic information of the surveyed subjects,the operation of the referral process for critically ill pregnant women(including familiarity and rationality of the referral process),referral indications,dif-ficulties and problems encountered during the referral process,etc.Results:①In this study,a total of 761 valid questionnaires were collected,of which 539 were from Beijing and 222 were from Chongqing.Among 761 surveyed individuals,physicians accounted for 51.4％and nurses(including midwives)accounted for 48.6％;39.7％of the cases came from third level midwifery institutions,while 60.3％came from second level or lower midwifery institu-tions.②93.1％of the surveyed medical staff were familiar with the referral process,with 92.8％in Beijing and 94.2％in Chongqing.There was no statistically significant difference between the two regions(x2=2.843,P=0.241);98.3％of the surveyed medical staff believed that the referral process in their unit was reasonable,with 98.9％in Beijing and 96.8％in Chongqing.There was no statistically significant difference between the two re-gions(x2=4.121,P=0.127).③ The main problems encountered by referral institutions were delayed patient ref-errals(51.0％)and unclear case reporting(42.9％),while the most common difficulties encountered by referral institutions were poor referral transportation(29.5％),inability to respond to referral requests in a timely manner(17.9％),and difficulties in inter hospital communication(17.7％).Conclusions:Medical staff in Beijing and Chongqing are familiar with the referral system for critically ill pregnant women and have achieved good operation-al results.In response to the main problems and difficulties in the current referral process,it is recommended to combine online and on-set consultations to promote continuous communication,standardize referral case records,establish a two-way referral model and regular feedback mechanism,and strengthen targeted personnel commu-nication.

Osteoporotic fractures are characterized by reduced bone mass and microstructural abnormalities, leading to differences in the healing process compared to traumatic fractures. The fracture healing process is generally divided into the inflammatory phase, the repair phase and the remodeling phase. In patients with osteoporotic fractures, due to factors such as decreased bone density, reduced bone quality and aging, there are partial alterations in inflammatory cells and osteoimmunity associated with those three healing phases, ultimately affecting fracture healing. This article focuses on the differences in fracture healing between non-osteoporotic fractures and osteoporotic fractures, reviewing relevant research literature and consensus. It analyzes and discusses changes in bone marrow mesenchymal stem cells and bone metabolism during osteoporosis, the effects of inflammatory aging, underlying diseases, and anti-osteoporosis medications on fracture healing, as well as the changes observed after pharmacological intervention. The aim is to emphasize personalized treatment approaches that account for individual and bone-specific factors in managing osteoporotic fractures, striving to promote better fracture healing outcomes and improving patients' quality of life.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To investigate the current status of referral for critically ill pregnant women in Beijing and Chongqing,provide improvement strategies for the management of referral for critically ill pregnant women.Meth-ods:From May 2022 to June 2024,a self-made questionnaire was used to survey medical staff at different levels of midwifery institutions in Beijing and Chongqing through the internet.The survey targets 18 midwifery institutions in Haidian District and Changping District of Beijing,as well as 50 midwifery institutions in 25 districts and counties of Chongqing.Collect and analyze basic information of the surveyed subjects,the operation of the referral process for critically ill pregnant women(including familiarity and rationality of the referral process),referral indications,dif-ficulties and problems encountered during the referral process,etc.Results:①In this study,a total of 761 valid questionnaires were collected,of which 539 were from Beijing and 222 were from Chongqing.Among 761 surveyed individuals,physicians accounted for 51.4％and nurses(including midwives)accounted for 48.6％;39.7％of the cases came from third level midwifery institutions,while 60.3％came from second level or lower midwifery institu-tions.②93.1％of the surveyed medical staff were familiar with the referral process,with 92.8％in Beijing and 94.2％in Chongqing.There was no statistically significant difference between the two regions(x2=2.843,P=0.241);98.3％of the surveyed medical staff believed that the referral process in their unit was reasonable,with 98.9％in Beijing and 96.8％in Chongqing.There was no statistically significant difference between the two re-gions(x2=4.121,P=0.127).③ The main problems encountered by referral institutions were delayed patient ref-errals(51.0％)and unclear case reporting(42.9％),while the most common difficulties encountered by referral institutions were poor referral transportation(29.5％),inability to respond to referral requests in a timely manner(17.9％),and difficulties in inter hospital communication(17.7％).Conclusions:Medical staff in Beijing and Chongqing are familiar with the referral system for critically ill pregnant women and have achieved good operation-al results.In response to the main problems and difficulties in the current referral process,it is recommended to combine online and on-set consultations to promote continuous communication,standardize referral case records,establish a two-way referral model and regular feedback mechanism,and strengthen targeted personnel commu-nication.

Traditional Chinese Medicine(TCM)emphasizes syndrome differentiation and treatment,characterized by"maintaining the prescription if effective"and"changing the prescription if ineffective".Traditional randomized controlled trials(RCTs)are inadequate for evaluating the efficacy of dynamic treatment adjustments.The Sequential Multiple Assignment Randomized Trial(SMART)is an emerging adaptive research design that incorporates randomization at multiple stages,allowing for adjustments in subsequent interventions based on treatment responses.This approach is suitable for evaluating dynamic treatment regimens while retaining the low bias risk of traditional RCTs,making it highly promising for clinical research in TCM.This paper summarizes recent methodological advancements in SMART design,including different sample size estimation and statistical analysis methods for primary effect objectives,embedded adaptive intervention objectives,and optimization objectives,along with providing corresponding operational software.Additionally,it offers considerations for applying SMART design in TCM research,such as the selection of disease types,interventions,decision points,tailoring variables,sample size calculation,statistical methods,the importance of pilot trials,ethical considerations,and limitations.The aim is to promote the exploration and practice of this method in the field of TCM,thereby contributing to the generation of high-quality evidence-based evidence for TCM.