ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Objective:To systematically analyze the disease burden of soft tissue and extraosseous sarcomas (STEOS) among individuals aged 15-49 years old worldwide and in the Chinese mainland from 1990 to 2021, and explore the relationship between socio-economic development and disease burden.Methods:Incidence, mortality and disability-adjusted life year (DALY) for STEOS in populations aged from 15 to 49 were collected from the Global Burden of Disease (GBD2021) database. The temporal trends in disease burden were quantified using the average annual percentage change (AAPC). The socio-demographic index (SDI) was employed to examine the socio-economic development.Results:The global incidence rate of STEOS among individuals aged 15-49 remained relatively stable (AAPC=-0.13, 95% CI:-0.23--0.04, P=0.299). In contrast, significant declines were observed in both mortality rate (AAPC=-0.39, 95% CI:-0.47--0.31, P<0.001) and DALY rate (AAPC=-0.46, 95% CI:-0.54--0.38, P<0.001). In the Chinese mainland, the incidence of STEOS among individuals aged 15-49 remained relatively stable (AAPC=-0.10, 95% CI:-0.31-0.10, P=0.314), while the mortality rate (AAPC=-1.42, 95% CI:-1.59--1.25, P<0.001) and DALY rate (AAPC=-1.62, 95% CI:-1.82--1.42, P<0.001) declined steadily from 1990 to 2021. In 2021, high-SDI regions reported high incidence rate (1.38/100 000, 95% UI:1.28/100 000-1.46/100 000), mortality rate (0.42/100 000, 95% UI:0.39/100 000-0.43/100 000) and DALY rate (23.05/100 000, 95% UI:21.84/100 000-24.00/100 000), while low-SDI regions reported high mortality rate (0.36/100 000, 95% UI:0.27/100 000-0.54/100 000) and DALY rate (20.50/100 000, 95% UI:15.46/100 000-30.96/100 000). Conclusion:The disease burden of STEOS worldwide and in the Chinese mainland populations aged from 15 to 49 has declined consistently. Notably, STEOS constitutes a substantial disease burden, particularly among countries and regions with high-SDI and low-SDI in 2021.

BACKGROUND:The AO12-C type middle-proximal humeral fractures are usually caused by high-energy injuries,accompanied by comminuted fractures and a large number of butterfly-shaped bone fragments.These fractures are difficult to achieve good reduction and effective fixation.With the increasing understanding of the biological characteristics of bone and soft tissue,surgical treatment is gradually shifting towards minimally invasive steel plates and intramedullary nail fixation.However,there has been no consensus on which is the best surgical technique for treating humeral fractures in minimal invasive plate osteosynthesis and intramedullary nail.OBJECTIVE:To compare the clinical effect of minimal invasive plate osteosynthesis and intramedullary nail for treating AO12-C type middle-proximal humeral fractures.METHODS:A retrospective analysis was performed in 36 patients with AO12-C type middle-proximal humeral fracture who met the inclusion criteria admitted to the Guizhou Hospital of Beijing Jishuitan Hospital from January 2020 to December 2022.All patients were assigned to minimal invasive plate osteosynthesis group(18 cases)and intramedullary nail group(18 cases)according to the surgical treatment plan.The minimal invasive plate osteosynthesis group received minimally invasive plate osteosynthesis based on preoperative planning assisted by 3D printing,while the intramedullary nail group received intramedullary nail internal fixation.Operation time,intraoperative blood loss,hospital stay,and fracture healing time were compared between the two groups.Visual analog scale score at 1,3,and 6 months after surgery,shoulder joint function,Constant-Murley score,Quick Disabilities of the Arm,Shoulder and Hand(QuickDASH)score,and complications of the shoulder joint at the last follow-up were compared between the two groups.RESULTS AND CONCLUSION:(1)All patients were followed-up for average(15.56±4.05)months,and no difference was observed in hospital stay and fracture healing time between the two groups(P＞0.05).The minimal invasive plate osteosynthesis group had shorter operation time compared to the intramedullary nail group(P＜0.05).The intramedullary nail group had less intraoperative blood loss between the two groups of patients(P＜0.05).(2)In the intramedullary nail group,at 1 and 3 months after operation,the visual analog scale score was significantly lower than the minimal invasive plate osteosynthesis group(P＜0.05).No difference was observed in the visual analog scale in long-term follow-up,shoulder joint function,Constant-Murley score,Quick Disabilities of the Arm,Shoulder and Hand(QuickDASH)score at the last follow-up between the two groups(P＞0.05).(3)No complications such as nonunion or wound infection occurred in either group.Two cases of radial nerve palsy occurred in minimal invasive plate osteosynthesis group,both of which recovered within 3 months.The intramedullary nail group had 1 case of rotator cuff injury.There was no significant difference in the rate of complications between the two groups(P＞0.05).(4)To conclude,minimal invasive plate osteosynthesis and intramedullary nail can achieve good clinical efficacy in the treatment of AO12-C type middle-proximal humeral fractures,effectively improving shoulder joint function in patients.However,minimal invasive plate osteosynthesis exhibits obvious advantages in shorter surgical time with the assistance of 3D printing,which is a valuable,effective,and safe method for treating AO12-C type middle-proximal humeral fractures.

Objective:To systematically analyze the disease burden of soft tissue and extraosseous sarcomas (STEOS) among individuals aged 15-49 years old worldwide and in the Chinese mainland from 1990 to 2021, and explore the relationship between socio-economic development and disease burden.Methods:Incidence, mortality and disability-adjusted life year (DALY) for STEOS in populations aged from 15 to 49 were collected from the Global Burden of Disease (GBD2021) database. The temporal trends in disease burden were quantified using the average annual percentage change (AAPC). The socio-demographic index (SDI) was employed to examine the socio-economic development.Results:The global incidence rate of STEOS among individuals aged 15-49 remained relatively stable (AAPC=-0.13, 95% CI:-0.23--0.04, P=0.299). In contrast, significant declines were observed in both mortality rate (AAPC=-0.39, 95% CI:-0.47--0.31, P<0.001) and DALY rate (AAPC=-0.46, 95% CI:-0.54--0.38, P<0.001). In the Chinese mainland, the incidence of STEOS among individuals aged 15-49 remained relatively stable (AAPC=-0.10, 95% CI:-0.31-0.10, P=0.314), while the mortality rate (AAPC=-1.42, 95% CI:-1.59--1.25, P<0.001) and DALY rate (AAPC=-1.62, 95% CI:-1.82--1.42, P<0.001) declined steadily from 1990 to 2021. In 2021, high-SDI regions reported high incidence rate (1.38/100 000, 95% UI:1.28/100 000-1.46/100 000), mortality rate (0.42/100 000, 95% UI:0.39/100 000-0.43/100 000) and DALY rate (23.05/100 000, 95% UI:21.84/100 000-24.00/100 000), while low-SDI regions reported high mortality rate (0.36/100 000, 95% UI:0.27/100 000-0.54/100 000) and DALY rate (20.50/100 000, 95% UI:15.46/100 000-30.96/100 000). Conclusion:The disease burden of STEOS worldwide and in the Chinese mainland populations aged from 15 to 49 has declined consistently. Notably, STEOS constitutes a substantial disease burden, particularly among countries and regions with high-SDI and low-SDI in 2021.

BACKGROUND:The AO12-C type middle-proximal humeral fractures are usually caused by high-energy injuries,accompanied by comminuted fractures and a large number of butterfly-shaped bone fragments.These fractures are difficult to achieve good reduction and effective fixation.With the increasing understanding of the biological characteristics of bone and soft tissue,surgical treatment is gradually shifting towards minimally invasive steel plates and intramedullary nail fixation.However,there has been no consensus on which is the best surgical technique for treating humeral fractures in minimal invasive plate osteosynthesis and intramedullary nail.OBJECTIVE:To compare the clinical effect of minimal invasive plate osteosynthesis and intramedullary nail for treating AO12-C type middle-proximal humeral fractures.METHODS:A retrospective analysis was performed in 36 patients with AO12-C type middle-proximal humeral fracture who met the inclusion criteria admitted to the Guizhou Hospital of Beijing Jishuitan Hospital from January 2020 to December 2022.All patients were assigned to minimal invasive plate osteosynthesis group(18 cases)and intramedullary nail group(18 cases)according to the surgical treatment plan.The minimal invasive plate osteosynthesis group received minimally invasive plate osteosynthesis based on preoperative planning assisted by 3D printing,while the intramedullary nail group received intramedullary nail internal fixation.Operation time,intraoperative blood loss,hospital stay,and fracture healing time were compared between the two groups.Visual analog scale score at 1,3,and 6 months after surgery,shoulder joint function,Constant-Murley score,Quick Disabilities of the Arm,Shoulder and Hand(QuickDASH)score,and complications of the shoulder joint at the last follow-up were compared between the two groups.RESULTS AND CONCLUSION:(1)All patients were followed-up for average(15.56±4.05)months,and no difference was observed in hospital stay and fracture healing time between the two groups(P＞0.05).The minimal invasive plate osteosynthesis group had shorter operation time compared to the intramedullary nail group(P＜0.05).The intramedullary nail group had less intraoperative blood loss between the two groups of patients(P＜0.05).(2)In the intramedullary nail group,at 1 and 3 months after operation,the visual analog scale score was significantly lower than the minimal invasive plate osteosynthesis group(P＜0.05).No difference was observed in the visual analog scale in long-term follow-up,shoulder joint function,Constant-Murley score,Quick Disabilities of the Arm,Shoulder and Hand(QuickDASH)score at the last follow-up between the two groups(P＞0.05).(3)No complications such as nonunion or wound infection occurred in either group.Two cases of radial nerve palsy occurred in minimal invasive plate osteosynthesis group,both of which recovered within 3 months.The intramedullary nail group had 1 case of rotator cuff injury.There was no significant difference in the rate of complications between the two groups(P＞0.05).(4)To conclude,minimal invasive plate osteosynthesis and intramedullary nail can achieve good clinical efficacy in the treatment of AO12-C type middle-proximal humeral fractures,effectively improving shoulder joint function in patients.However,minimal invasive plate osteosynthesis exhibits obvious advantages in shorter surgical time with the assistance of 3D printing,which is a valuable,effective,and safe method for treating AO12-C type middle-proximal humeral fractures.

In the era of evidence-based medicine, it is necessary to explore the unique advantages of traditional Chinese medicine (TCM) based on standardized technical methods and operating procedures in order to achieve the modernization and internationalization of TCM and benefit all humanity. The proposal of a three-pronged evidence system combining TCM theory, human experience and experimental evidence marks an important progress in the thinking method of the TCM evaluation system. The multi-evidence body integrated through appropriate methods provides a strong support for the clinical guideline recommendations and evidence-based health decision-making in TCM. Based on the current methodological progress of international evidence synthesis and grading, this paper proposes a novel approach for integrating multi-evidence in TCM: the MERGE framework. The aim is to establish a solid foundation for the development of this methodology and provide guidance for the advancement of evidence-based medicine framework in TCM.

Methods: From May 2021 to August 2021, panelists were chosen to collect expert feedback using the modified Delphi method, and 74 spine surgeons from across China agreed to participate. Four rounds were conducted: one in-person meeting and three subsequent survey rounds. Each question received at least 70.0% agreement, indicating a consensus. The grade A, B, and C recommendation were defined as having ≥90.0%, 80.0%–89.9%, and 70.0%–79.9% agreement on each question, respectively. Results: The panelist group consisted of 74 experts, and 72, 70, and 69 questionnaires were collected in three rounds, respectively. In total, 24 questions with 59 options reached consensus after the Delphi rounds, including indications (adjacent vertebral diseases after lumbar internal fixation) and contraindications (previous surgery or bone destructive diseases lead to the destruction or absence of bone in the lamina or isthmus); advantages (intraoperative traction of paravertebral soft tissue is small) and disadvantages (not three-column fixation.); preoperative evaluation; complications; and postoperative follow-up evaluation, of CBT. Conclusions The modified Delphi method achieved expert consensus on the clinical use of CBT for lumbar pedicle screws. This consensus document establishes clear guidelines for indications, contraindications, surgical techniques, and postoperative management, thereby enhancing clinical decision-making and promoting the safe and effective use of CBT. While the initial study focused on Chinese surgeons, future research will seek to validate and expand these findings from a broader international perspective.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.