OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China， providing a reference for promoting enterprise R&D and production， as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval， Pharnexcloud biomedical database， and National Medical Insurance Drug Directory， this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30， 2024， a total of 68 pediatric medicines had been approved through the priority review and approval process， covering 12 therapeutic areas， with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days， with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years， with an average of 1.42 years. This included 12 domestic new medicines， 21 domestic generic medicines， 35 imported medicines， as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally， 31 of these medicines had been included in the medical insurance catalog， representing a proportion of 45.59%. CONCLUSIONS Currently， a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding， and the dosage forms are becoming more tailored to children’s needs. However， there are still issues such as slow progress in new medicine development， insufficient stability in the medicine review and approval process， and a need to increase the proportion of medicines included in medical insurance.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

With the increasing average life expectancy and the growing global aging population, cognitive frailty in the elderly has emerged as a new concept and a key focus of research in geriatrics.Cognitive frailty shows potential for reversibility, and early screening and intervention can have a positive impact on either recovering or slowing down cognitive decline in older adults, making it a promising target for promoting healthy aging.However, research on cognitive frailty is still in its nascent stages, and there is no consensus on its definition and screening criteria.This review provides an overview of the current research progress on the definition, epidemiological status, assessment tools, influencing factors, and intervention strategies for cognitive frailty.The aim is to enhance healthcare professionals' understanding of cognitive frailty in the elderly and improve diagnostic, treatment, and prevention approaches.

Objective To investigate the predictive value of serum 25-hydroxyvitamin D[25(OH)D]level in early renal transplantation for acute rejection(AR).Methods A total of 324 renal transplant recipients from January 2019 to August 2022 in the Second People's Hospital of Shanxi Province were selected.The clinical data of the recipients were collected.The levels of serum 25(OH)D,parathyroid hormone(PTH),and calcium,phosphorus in early(within 1 month)transplantation were detected by chemiluminescence immunoassay and colorimetry,respectively.The detection season was recorded,and the occurrence of AR within 1 year after renal transplantation was observed.The 25(OH)D level ≥ 20ng/ml was defined as normal,≥ 12 ng/ml～＜20 ng/ml as insufficient and＜12ng/ml as deficient,they were divided into of 25(OH)D normal group(n=106),insufficient group(n=112)and deficient group(n=106).According to the occurrence of AR,they were divided into AR group(n=51)and non-AR group(n=273).The basic situation of serum 25(OH)D level was analyzed.The differences in serum PTH,calcium,phosphorus levels and seasons as well as AR incidence among the three groups of 25(OH)D were compared.Multivariate logistic regression was used to analyze the influencing factors of AR,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum 25(OH)D level for AR.Results The incidence of serum 25(OH)D deficiency or insufficiency was 67.28％(218/324).In the 25(OH)D normal group,insufficient group and deficiency group,the serum PTH levels were 75.44(46.42,113.23)pg/ml,78.29(58.27,152.10)pg/ml and 86.84(54.64,127.3)pg/ml,and the incidences of AR were 2.47％(8/324),6.17％(20/324)and 7.10％(23/324),respectively.All of them were the highest in the deficiency group and the lowest in the normal group,and the differences were significant(H=6.784,x2=8.580,all P＜0.05).Additionally,25(OH)D deficiency(OR=3.340,95％CI:1.409～7.916),25(OH)D insufficiency(OR=2.442,95％CI:1.006～5.925)and human leucocyte antigen(HLA)mismatch(4～6)(OR=2.117,95％CI:1.027～4.363)were independent risk factors for AR(all P＜0.05).The area under the curve(AUC)of serum 25(OH)D level in predicting AR was 0.702(95％CI:0.625～0.779),the optimal cut-off value was 13.59 ng/ml,the specificity and the sensitivity were 66.7％and 65.6％,respectively.Conclusion In this study,25(OH)D deficiency(＜12ng/ml)or insufficiency(≥ 12～＜20ng/ml)was an independent risk factor for AR,and serum 25(OH)D level may have a certain predictive value for AR.

Objective:To explore the efficacy and safety of in-class transition from proteasome inhibitor bortezomib to ixazomib in the treatment of newly-treated patients with multiple myeloma (MM).Methods:The clinical data of 63 newly-treated MM patients in Shenzhen Second People's Hospital from January 2018 to December 2020 were retrospectively analyzed. They were divided into transition group (23 cases) and bortezomib group (40 cases). Both groups were treated with bortezomib-containing regimen as the first-line treatment regimen. In case of intolerable adverse reactions, patients in the transition group were treated with ixazomib instead of bortezomib, while the patients in the bortezomib group did not undergo drug transition. The curative effect and progression-free survival (PFS) were compared between the two groups.Results:In the transition group, the overall response rate (ORR) before in-class transition was 95.7% (22/23), the rate of ≥ very good partial remission (VGPR) was 52.2% (12/23); the ORR after transition was 95.7% (22/23), and the rate of ≥ VGPR was 82.6% (19/23). In the bortezomib group, ORR was 90.0% (36/40), and the rate of ≥ VGPR was 72.5% (29/40). There was no significant difference in ORR and the rate of ≥VGPR between the two groups ( χ2 = 0.64, P=0.424; χ2 = 0.82, P = 0.364). The median number of cycles of PI therapy in the transition group was 9, and the median PFS time was not reached. The median number of cycles of PI therapy in the bortezomib group was 7.5, and the median PFS time was 30.0 months (95% CI 19.1-40.9 months), there was no significant difference in PFS between the two groups ( P = 0.275). In the bortezomib group, 12 patients discontinued bortezomib due to adverse reactions, the median PFS time was 20.0 months (95% CI 12.6-27.4 months), and the PFS of patients who discontinued PI in the transition group and the bortezomib group was compared, the difference was statistically significant ( P = 0.043). In the transition group, 21 patients (21/23, 91.3%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 13.0% (3/23); in the bortezomib group, 22 patients (22/40, 55.0%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 12.5% (5/40). Conclusions:For newly-treated MM patients, the transition from bortezomib to ixazomib can improve the depth of remission and reduce the recurrence caused by the discontinuation of PI.

Objective:To evaluate the efficacy and safety of azacitidine combined with HAG regimen in the treatment of newly diagnosed elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy.Methods:Eighteen newly diagnosed elderly AML patients ineligible for intensive chemotherapy from July 2019 to September 2021 in the Second People's Hospital of Shenzhen were prospectively enrolled in this study. They were non-randomly divided into azacitidine combined with HAG regimen (AZA-HAG) group (9 cases) and decitabine combined with HAG regimen (DEC-HAG) group (9 cases). The primary endpoint of the study was overall response [complete remission (CR)+partial remission], and the secondary endpoints included CR + complete remission with incomplete count recovery (CRi), overall survival (OS) and drug safety. Kaplan-Meier method was used to analyze the OS.Results:The median age of 18 patients was 67 years old (60-77 years old) , and 8 of them were in high-risk group. After one course of treatment, the overall response and CR+CRi were observed in 7 of 9 patients in AZA-HAG group, and they were observed in 8 of 9 patients in DEC-HAG group, and there was no significant difference between the two groups (both P = 1.000). The median duration of CR+CRi was 7 months in both groups, and the median OS time was 12 months in both groups; there was no significant difference in OS between the two groups ( χ2 = 0.02, P = 0.895). In AZA-HAG group, 1 patient with TP53 mutation and 1 patient with ASXL1+RUNX1 mutation acquired CR, and 1 patient with NPM1 wild-type combined with FLT3-ITD and ASXL1 mutation did not respond. There was no significant difference in the incidence of grade 3-4 hematological adverse reactions between the two groups (all P < 0.05). Conclusions:Azacitidine combined with low-dose HAG regimen in the treatment of newly diagnosed elderly AML patients ineligible for intensive chemotherapy has satisfactory efficacy and long-term survival, and the adverse reactions can be tolerated.

Objective:To investigate the therapeutic effect of venetoclax combined with azacitidine in treatment of myelodysplastic syndromes (MDS) complicated with monoclonal globulinemia of unknown significance (MGUS).Methods:The clinical data of a patient with MDS complicated with MGUS in the Second People's Hospital of Shenzhen in December 2020 were retrospectively analyzed, and the literatures were reviewed.Results:According to results of bone marrow smear, cytogenetics, and next-generation sequencing, the patient was diagnosed as MDS and MGUS complicated with ASXL1, RUNX1, EZH2, STAG2 mutations as well as t(11;14). No response was observed after 2 courses of azacitidine and 1 course of azacitidine plus HAG. Later the patient achieved complete remission and negative RUNX1 and STAG2 mutations after a course of venetoclax combined with azacitidine. Meanwhile, M protein exhibited a decrease more than 50%. To date, the patient was still in complete remission.Conclusions:The regimen of venetoclax combined with azacitidine shows a significant efficacy and good tolerance to patient with co-occurrence of MDS and MGUS with t(11; 14).