Objective:To investigate expression levels of various myeloid suppressor cells(MDSCs)in bone marrow of patients with chronic myeloid leukemia(CML),and the difference and correlation of expression levels of BCR-ABL fusion gene and WT1 in CML patients at different stages,and explore its clinical significance.To analyze and compare the distribution differences of various MDSCs in CML with different remission depths after treatment.Methods:Proportions of various MDSCs in 58 CML patients were de-tected by flow cytometry.Relative expressions of WT1 and BCR-ABL were detected by RQ-PCR.Iron deficiency anemia patients were served as control group,differences of the distribution of MDSCs in CML patients with different BCR-ABL expression,different WT1 expression,different CD34+cell numbers and different disease course,and expressions of various types of MDSC at 3,6,12 and 24 months after treatment in patients with chronic phase of CML were analyzed.At the same time,changes of cellular immune status in CML patients at different stages were detected,and correlations between the changes of lymphocyte subsets and MDSCs were compared.Results:Proportions of G-MDSC and e-MDSC in chronic phase of CML were significantly higher than that in normal control group(P<0.05).Proportions of G-MDSC and e-MDSC in CML patients in accelerated phase and blast crisis phase were significantly higher than that in CML patients in chronic phase(P<0.05).However,the difference in proportion of M-MDSC between accelerated phase of CML and chronic phase of CML had no statistical significance.Proportion of G-MDSC in CML patients was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.558 7,0.530 7,0.598 1),proportion of M-MDSC was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.132 1,0.144 6,0.157 8).Proportion of e-MDSC was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.604 3,0.620 7,0.625 9).G-MDSC was significantly lower in the best response group than that in warning/failure group at all stages of treatment.e-MDSC was differential in the best response and warning/failure groups at only 3 months of treatment.M-MDSC was not statistically significant in the best response and warning/failure groups at all stages of treatment.And only G-MDSC cell ratio was positively correlated with its BCR-ABL ratio(r=0.798 1).Per-centage of T lymphocyte in CML blast crisis phase was significantly lower than that in accelerated and chronic phases,while percentage of NK cells was higher.Only the proportion of G-MDSC was negatively correlated with the proportion of T lymphocyte(r=-0.815 2).Conclusion:Various MDSCs are positively correlated with BCR-ABL,WT1 gene and CD34+cells,and positively correlated with the tumor burden of CML patients,while the correlation of M-MDSC is weaker than that of G-MDSC and e-MDSC.With the remission of CML,G-MDSC decreases,while M-MDSC does not change.e-MDSC only shows differences in the early 3-month of treatment.Change of G-MDSC ratio may predict the effect of CML treatment.MDSCs can inhibit the proliferation of T lymphocyte,and inhibitory effect of G-MDSC is stronger than that of M-MDSC and e-MDSC.

Guidelines, consensuses and standards play a significant role in guiding clinical diagnosis and treatment practices, optimizing the allocation of medical resources and reducing medical costs. To fully leverage the pivotal role of the National Clinical Research Center as a bridge between research evidence, recommendations of guidelines, consensuses and standards, and clinical practice, it is particularly urgent to construct a set of appropriate and efficient management system for guidelines, consensuses and standards. The National Clinical Research Center for Geriatric of West China Hospital, Sichuan University (hereinafter referred to as the center) has set the overall goal of " transparency, standardization, coordination, linkage and innovation leadership" and three phased goals of " achieving scientific, transparent and applicable management" " improving the multi-level, multi-subject coordination and linkage mechanism" and " promoting the homogenization of diagnosis and treatment services, process guarantee and standardized management" to explore the establishment of a management system for guidelines, consensuses and standards. Under this framework, the center has established the management committee and office for guidelines, consensuses and standards; build a dual-channel funding support model of " out-of-hospital+ in-hospital", established differentiated implementation models and formulated standardized processes; respectively formed clinical expert groups, methodology expert groups and evidence synthesis working groups, and carried out personnel training; and constructed a support platform for formulation, evaluation and promotion. As of October 2024, relying on the established management system for guidelines, consensuses and standards, the center has achieved a series of results in three aspects: formulating international evidence-based clinical practice guidelines, establishing a system of guidelines, consensuses and standards for geriatric disability, and building a standard system for medical and nursing integration, which has strongly supported clinical practice and the improvement of people′s livelihood by the government, and preliminarily completed the construction goals of the first phase, and can provide references for medical institutions committed to building a management system for guidelines, consensuses and standards.

Objective:To investigate expression levels of various myeloid suppressor cells(MDSCs)in bone marrow of patients with chronic myeloid leukemia(CML),and the difference and correlation of expression levels of BCR-ABL fusion gene and WT1 in CML patients at different stages,and explore its clinical significance.To analyze and compare the distribution differences of various MDSCs in CML with different remission depths after treatment.Methods:Proportions of various MDSCs in 58 CML patients were de-tected by flow cytometry.Relative expressions of WT1 and BCR-ABL were detected by RQ-PCR.Iron deficiency anemia patients were served as control group,differences of the distribution of MDSCs in CML patients with different BCR-ABL expression,different WT1 expression,different CD34+cell numbers and different disease course,and expressions of various types of MDSC at 3,6,12 and 24 months after treatment in patients with chronic phase of CML were analyzed.At the same time,changes of cellular immune status in CML patients at different stages were detected,and correlations between the changes of lymphocyte subsets and MDSCs were compared.Results:Proportions of G-MDSC and e-MDSC in chronic phase of CML were significantly higher than that in normal control group(P<0.05).Proportions of G-MDSC and e-MDSC in CML patients in accelerated phase and blast crisis phase were significantly higher than that in CML patients in chronic phase(P<0.05).However,the difference in proportion of M-MDSC between accelerated phase of CML and chronic phase of CML had no statistical significance.Proportion of G-MDSC in CML patients was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.558 7,0.530 7,0.598 1),proportion of M-MDSC was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.132 1,0.144 6,0.157 8).Proportion of e-MDSC was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.604 3,0.620 7,0.625 9).G-MDSC was significantly lower in the best response group than that in warning/failure group at all stages of treatment.e-MDSC was differential in the best response and warning/failure groups at only 3 months of treatment.M-MDSC was not statistically significant in the best response and warning/failure groups at all stages of treatment.And only G-MDSC cell ratio was positively correlated with its BCR-ABL ratio(r=0.798 1).Per-centage of T lymphocyte in CML blast crisis phase was significantly lower than that in accelerated and chronic phases,while percentage of NK cells was higher.Only the proportion of G-MDSC was negatively correlated with the proportion of T lymphocyte(r=-0.815 2).Conclusion:Various MDSCs are positively correlated with BCR-ABL,WT1 gene and CD34+cells,and positively correlated with the tumor burden of CML patients,while the correlation of M-MDSC is weaker than that of G-MDSC and e-MDSC.With the remission of CML,G-MDSC decreases,while M-MDSC does not change.e-MDSC only shows differences in the early 3-month of treatment.Change of G-MDSC ratio may predict the effect of CML treatment.MDSCs can inhibit the proliferation of T lymphocyte,and inhibitory effect of G-MDSC is stronger than that of M-MDSC and e-MDSC.

Guidelines, consensuses and standards play a significant role in guiding clinical diagnosis and treatment practices, optimizing the allocation of medical resources and reducing medical costs. To fully leverage the pivotal role of the National Clinical Research Center as a bridge between research evidence, recommendations of guidelines, consensuses and standards, and clinical practice, it is particularly urgent to construct a set of appropriate and efficient management system for guidelines, consensuses and standards. The National Clinical Research Center for Geriatric of West China Hospital, Sichuan University (hereinafter referred to as the center) has set the overall goal of " transparency, standardization, coordination, linkage and innovation leadership" and three phased goals of " achieving scientific, transparent and applicable management" " improving the multi-level, multi-subject coordination and linkage mechanism" and " promoting the homogenization of diagnosis and treatment services, process guarantee and standardized management" to explore the establishment of a management system for guidelines, consensuses and standards. Under this framework, the center has established the management committee and office for guidelines, consensuses and standards; build a dual-channel funding support model of " out-of-hospital+ in-hospital", established differentiated implementation models and formulated standardized processes; respectively formed clinical expert groups, methodology expert groups and evidence synthesis working groups, and carried out personnel training; and constructed a support platform for formulation, evaluation and promotion. As of October 2024, relying on the established management system for guidelines, consensuses and standards, the center has achieved a series of results in three aspects: formulating international evidence-based clinical practice guidelines, establishing a system of guidelines, consensuses and standards for geriatric disability, and building a standard system for medical and nursing integration, which has strongly supported clinical practice and the improvement of people′s livelihood by the government, and preliminarily completed the construction goals of the first phase, and can provide references for medical institutions committed to building a management system for guidelines, consensuses and standards.

OBJECTIVE To investigate the variations in taste， aroma and volatile organic compounds of Rhei Radix et Rhizoma decoction pieces derived from different sources， and to identify their origins. METHODS The flavor， odor and volatile organic compounds of Rhei Radix et Rhizoma decoction pieces from different sources were compared and analyzed by using electronic tongue， electronic nose， and gas chromatography-ion mobility spectrometry （GC-IMS）. Principal component analysis （PCA）， partial least squares-discriminant analysis （PLS-DA）， orthogonal partial least squares discriminant analysis （OPLS-DA） and Fisher discriminant analysis were employed to identify the origins of Rhei Radix et Rhizoma decoction pieces and establish the basis discrimination criteria. RESULTS The differences in taste of Rhei Radix et Rhizoma decoction pieces from 3 origins were primarily characterized by bitterness， astringency， and bitter-astringent aftertaste. In terms of smell， variations were mainly observed in inorganic sulfides， organic sulfides containing aromatic components， methane and other short-chain alkanes， alcohols， ethers， aldehydes and ketones， as well as nitrogen oxides. Differentially volatile organic compounds mainly consisted of alcohols， aldehydes and ketones. Furthermore， the samples from 8 batches could be effectively classified into 3 categories.Three types of Rhei Radix et Rhizoma decoction pieces can be effectivily identified based on the peak intensity ratio between volatile substances. For example， when the peak intensity of 2-acetylfuran was 3-19 times that of isobutyric acid [dimer]， it was considered as Rheum officinale Baill. CONCLUSIONS The discriminant models established in this study， along with the criteria for determining the origins based on the peak intensity ofcharacteristic volatile compounds， can be utilized for the identification of Rhei Radix et Rhizoma decoction pieces.

Objective:To delineate the surgical methodology and therapeutic paradigm of proximal tibial notch retrograde interlocking intramedullary nailing for ameliorating deformities due to osteofibrous dysplasia (OFD) in a pediatric population.Methods:A retrospective assessment was conducted on the medical records of individuals undergoing orthopedic osteotomy complemented by retrograde interlocking intramedullary nailing for OFD of the tibia from January 2016 to December 2019. The cohort comprised 15 patients, with a follow-up exceeding three years, documenting complete data sets. The patient profile included 8 males and 7 females, with 8 left-side and 7 right-side afflictions. The mean age at the time of surgery was 10.1±2.5 years, ranging from 7.1 to 12.6 years. Parameters measured were preoperative and postoperative imaging findings, which encompassed the scope of the lesion (longitudinal lesion length relative to tibial length), coronal and sagittal limb alignments, and lower limb length discrepancies.Results:The mean follow-up duration was 3.4±1.3 years, ranging from 3 to 6.6 years. Preoperatively, prominent anterior tibial arch deformities and limping were present, with 7 cases reporting fatigue-induced pain and 3 instances of pathological fractures. Post-surgery, pain symptoms were resolved, gait disturbances were improved in 9 patients, and completely resolved in 6. Tibial osteotomy or fracture healing of 15 patients averaged 3.9±0.7 months (range 3-5 months). The lesion range before surgery was 0.41±0.17, immediately after surgery was 0.38±0.17, and at the last follow-up was 0.30±0.16, with no statistical significance ( F=0.101, P=0.904). Lesion range showed no significant change throughout treatment, but radiographic density within the lesion notably increased post-surgery, suggesting bone improvement. The anterior tibial arch Angle was 28.30°±6.62° (range 20°-45°) before surgery, 4.73°±1.53° immediately after surgery, and 6.87°±1.36° at the last follow-up, with statistical significance ( F=159.739, P<0.001). A significant correction in the anterior tibial arch deformity was achieved and maintained postoperatively. There was no significant angular deformity of the tibia in the coronal plane before operation, and the medial proximal tibial angle (MPTA) and lateral distal tibial angle (LDTA) were 87.50°±1.46° and 88.30°±1.62°, 88.40°±1.46° and 88.70°±1.45° immediately after surgery, and 88.00°±1.39° and 89.10°±1.53° at the last follow-up, the differences were statistically significant ( F=1.741, P=0.188; F=1.016, P=0.371), there was no coronal deformity of tibia. The limb length discrepancy (LLD) was 0.60±0.98 cm before surgery, 0.18±0.93 cm at the last follow-up, with statistical significance ( t=0.096, P=0.761). There were no incidents of postoperative complications such as infection. Conclusion:In pediatric cases of tibial deformities attributed to osteofibrous dysplasia, a therapeutic strategy involving osteotomy for lower limb realignment, sans curettage or bone grafting of the lesion, followed by retrograde interlocking intramedullary nailing, yields favorable outcomes. Importantly, this implantation technique does not compromise the integrity of the proximal tibial epiphyseal plate in children and adolescents.

Objective:To explore the clinical effect of plating after lengthening to assist the consolidation of tibial shortening deformity in children.Methods:A retrospective analysis was conducted on 10 children with tibial shortening who were treated with circular external fixator lengthening and replacement with plate-assisted internal fixation (study group) in the Department of Pediatric Orthopedics of Tianjin Hospital from November 2019 to October 2022, and 16 children who were treated by circular external fixator only during the same period were enrolled as the external fixator group (control group). Among the 26 cases, there were 15 males and 11 females, 10 left knees and 16 right knees. The average age at the time of surgery was 8.8±4.7 years (range 5.1-13.8 years). The gender, side, age at the time of surgery were compared between the two groups. The extension length, external fixator index, healing index, Kolcaba comfort scale score, knee and ankle joint range of motion, complications and average total hospitalization costs were recorded.Results:There were no significant differences in gender, side, age at the time of surgery between the study group and control group. The extended lengths were 5.44±1.25 cm and 5.78±1.11 cm respectively without significant difference ( t=0.096, P=0.096). The external fixator index and healing index were 17.86±2.94 d/cm vs. 50.97±7.03 d/cm and 40.94±6.63 d/cm vs. 45.24±5.98 d/cm in study group and the control group with significant differences ( t=13.299, P<0.001; t=1.289, P=0.033). The Kolcaba comfort scale score of the children in the study group was higher than that of the control group, with significant difference ( t=6.821, P=0.001). Comparing the range of motion of the knee and ankle joints between the two groups, there were no significant differences before surgery, at the end of extension surgery, and at the final follow-up. When the extension end was healed, the range of motion of the knee joint was137.89°±4.40° vs. 114.09°±13.60° and ankle joint was 64.35°±5.50° vs. 56.65°±8.86° in the study group and control group with significant difference ( t=17.235, P<0.001; t=7.821, P=0.002). In the study group, 4 cases had pin tract infection, but no refracture occurred; in the control group, pin tract infection occurred in 13 cases, and refracture occurred in 2 cases after removal of the external fixator. The average total hospitalization cost of the study group was higher than that of the control group with significant difference ( t=3.745, P=0.036). Conclusion:The clinical effect of replacing plate-assisted internal fixator during the mineralization period of tibial shortening in children is reliable, and can significantly shorten the time for using external fixator. It is beneficial to the healing of the extended end of the osteotomy and the functional recovery of the knee and ankle joints. Being more comfortable for children with fewer complications, it is applicable for children who need long-distance extension, multiple extensions with limited joint function, poor tolerance for external fixators and low treatment compliance.

The rapid development of big data and artificial intelligence technologies has propelled the large-scale, multi-center, and diverse forms of clinical research, and how to efficiently integrate and utilize clinical research data resources has become an urgent problem to be solved. Based on the U. S. geological survey(USGS) scientific data life cycle model, the National Clinical Research Center for Geriatrics has devised the " S-C-V-C-R-A" data management platform framework, which determined six data management principles: Standardization, Controllability, Visibility, Credibility, Reliability, and Availability. By solving three key technologies: data aggregation, data standardization, and data sharing, an integrated clinical research data platform was built to realize standardized data management plans, controllable data acquisition, visible data processing, credible data analysis, reliable data storage, and accessible data publication and sharing. As of July 2023, the platform has aggregated data from 487 096 elderly patients, carried out more than 10 scientific research projects, supported over 200 collaborative innovation network units, and established four cohorts of elderly populations with distinct characteristics. The platform has achieved a one-stop, comprehensive service of data management planning, acquisition, processing, analysis, storage, publication, and sharing, thus achieving the objectives of enhancing research efficiency, promoting collaborative research, and facilitating data sharing.

Open fund projects play an important role in strengthening discipline construction and enhancing research capabilities. The National Clinical Research Center for Geriatrics of West China Hospital, Sichuan University (hereinafter referred to as the Center) initiated the establishment of open fund projects in 2018. However, due to their strong disciplinary and autonomous nature, as well as the presence of uncertainty, these projects posed new challenges to project management. Therefore, based on the theory of project integration management, the Center has established an integrated management system for open fund projects. This system was achieved by identifying the construction objectives of open fund projects, defining their scope of application, and integrating the four essential elements of project management: execution, processes, control, and support. It ensured standardized execution through organizational and institutional measures, optimized management processes, implemented control through the development of milestone lists, risk registration lists, superior funding lists, and non-performing lists, and integrated technology and platforms as support. The system was implemented since 2020, realizing comprehensive and holistic management of open fund projects across all stages and elements, thereby effectively enhancing management efficiency and quality. As of December 2023, 112 open fund projects have been approved, with a total funding of 31.943 million yuan. These projects have yielded a series of achievements in cohort study and platform construction, academic output, and have demonstrated remarkable effectiveness in projects and talents cultivation. The construction and application of this system can provide reference for medical institutions in managing open fund projects.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.