OBJECTIVE: To compare the effectiveness of ultrasound-guided closed reduction with Kirschner wire fixation and open reduction with Kirschner wire fixation in the treatment of humeral lateral condyle fracture (HLCF) in children. METHODS: A clinical data of 53 children with HLCF admitted between May 2020 and April 2023 and met selective criteria was retrospectively analyzed. Of these, 25 cases were managed with closed reduction and Kirschner wire fixation under ultrasound guidance (closed group), while 28 cases underwent open reduction and Kirschner wire fixation (open group). There was no significant difference between the two groups in terms of gender, age, cause of injury, fracture side, fracture classification, and time from injury to operation ( P>0.05). The following variables were recorded and compared between the two groups: operation time, intraoperative fluoroscopy frequency, fracture healing time, incidence of complications, and the Flynn elbow function score at last follow-up. RESULTS: In the closed group, the fractures were successfully reduced under ultrasound guidance, with no nerve damage reported in either group. The operation time and intraoperative fluoroscopy frequency were significantly less in the closed group than in the open group ( P<0.05). One case of infection (Kirschner wire irritation) was observed in the closed group, while 3 cases in the open group (2 of Kirschner wire irritation and 1 of incision infection). However, the difference in the incidence of infection between the two groups was not significant ( P>0.05). All patients in both groups were followed up 6-18 months (mean, 10.2 months). X-ray examinations confirmed that fractures had healed in both groups, with no significant difference in healing time ( P>0.05). During follow-up, 5 cases of lateral humeral process formation were observed in the closed group, compared to 12 cases in the open group, although this difference was not significant ( P>0.05). At last follow-up, the excellent and good rate of elbow joint function was evaluated as 96.0% (24/25) in the closed group and 92.9% (26/28) in the open group according to the Flynn scoring criteria, with no significant difference between the two groups ( P>0.05). Both groups showed no occurrence of ossifying myositis or elbow internal/external rotation. CONCLUSION The effectiveness of ultrasound-guided closed reduction and Kirschner wire fixation in the treatment of HLCF in children is comparable to open reduction and Kirschner wire fixation, but the former can reduce operation time and intraoperative fluoroscopy frequency, and obtain lower the incidence of complications.
Humans ; Humeral Fractures/diagnostic imaging* ; Bone Wires ; Male ; Female ; Child ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Treatment Outcome ; Child, Preschool ; Open Fracture Reduction/methods* ; Fracture Healing ; Elbow Joint/surgery* ; Adolescent ; Closed Fracture Reduction/methods* ; Fluoroscopy ; Operative Time

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

ObjectiveTo systematically evaluate the distribution of traditional Chinese medicine（TCM） syndromes of primary osteoporosis（POP） in China by using evidence-based medicine methods， and to understand the distribution law of the syndromes. MethodChina National Knowledge Infrastructure（CNKI）， VIP Chinese Science and Technology Journal Database（VIP）， WanFang Data Knowledge Service Platform（WanFang） and China Biology Medicine（CBM） were searched to obtain representative literature， and each database was searched from the 1994 World Health Organization defined diagnostic criteria for osteoporosis until May 1， 2023. Two researchers independently screened literature according to the criteria， extracted data， and cross-checked them. Meta analysis was conducted using R4.1.3， and subgroup analysis was performed. ResultA total of 56 Chinese papers were included， involving 14 415 patients. After standardized classification of syndromes， 11 articles were excluded， and Meta analysis results of the ultimately included 45 Chinese articles showed that the distribution frequencies of liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome in 12 723 patients were 27%［95% confidence interval（CI） 0.24-0.31］， 32%（95% CI 0.29-0.36）， 36%（95% CI 0.30-0.42）. Subgroup analysis showed that there was a statistically significant difference in the distribution of the three TCM syndromes in the north and south（P<0.05）. In addition， the incidence of TCM syndrome fractures in different types of POP was 15%（95% CI 0.09-0.24） for liver-kidney Yin deficiency syndrome， 20%（95% CI 0.12-0.30） for spleen-kidney Yang deficiency syndrome， and 31%（95% CI 0.25-0.39） for kidney deficiency and blood stasis syndrome. ConclusionThe distribution of syndromes in POP patients is mainly kidney deficiency， accompanied by liver and spleen dysfunction. Liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome are all the main syndromes of POP and osteoporotic fractures， and kidney deficiency and blood stasis syndrome is most closely related to the development of osteoporotic fractures. The reference standards for syndrome determination among the included studies are inconsistent， and in the future， it is necessary to focus on their determination standards to obtain consensus research results， at the same time， conduct large-scale syndrome research to obtain representative research results， providing a basis for clinical practice and research.

Evoked Potentials ; Social Isolation ; Attention ; Humans

With a global rise in morbidity rates， obesity has become a pressing public health issue. With increased adipocyte number and volume as the main characteristics， obesity is also manifested by metabolic disorders to varying degrees. At the same time， obesity is a risk factor for diabetes， hypertension， stroke， cancer， and cardiovascular diseases， imposing burdens on society and families. Influenced by lifestyle， environment， behavior， and genetics， obesity is caused by the interaction of many factors， and its pathological process is complex， involving inflammation， autophagy， and intestinal dysbiosis. The mitogen-activated protein kinase （MAPK） cascade reaction， a pivotal signaling pathway， plays a crucial role in cellular processes such as proliferation， differentiation， apoptosis， and stress responses. Both Chinese and international studies indicate that the MAPK signaling pathway can effectively regulate obesity through various pathways， including the modulation of adipocyte differentiation and apoptosis， appetite control， and inflammation improvement. Moreover， traditional Chinese medicine （TCM） has demonstrated significant efficacy in preventing and treating obesity， leveraging advantages such as multiple targets， diverse components， and minimal adverse effects. Research indicates that the MAPK signaling pathway is a primary focus of TCM regulation in this context， although a systematic review in this field is currently lacking. Therefore， this paper， by reviewing the latest Chinese and international research， provided a concise overview of the basic structure of the MAPK pathway， with a specific emphasis on recent progress in TCM interventions targeting the MAPK pathway for obesity treatment. The results indicate that regulating adipose tissue formation， differentiation， and thermogenesis， reducing inflammation and oxidative stress levels， and improving insulin sensitivity and metabolic disorders seem to be the main ways for TCM to regulate the MAPK pathway to prevent and treat obesity. However， it is necessary to find more research methods and explore potential mechanisms underlying TCM formulations based on the MAPK pathway for obesity prevention and treatment.

Objective:To investigate the genetic and evolutionary characteristics of hemagglutinin (HA) and neuraminidase (NA) genes of influenza B/Victoria (BV) virus in Xi′an city from 2019 to 2023.Methods:Twenty-five BV strains isolated from the Xi′an influenza surveillance network laboratory between 2019 and 2023 were collected. The HA and NA genes were sequenced using MiniSeq high-throughput sequencing platform. An evolutionary tree was constructed using bioinformatics software to analyze homology and mutation sites, and to predict N-glycosylation sites online. The antigenicity of the strains was analyzed through hemagglutination inhibition tests.Results:The BV influenza in Xi′an exhibited a distinct seasonal transmission pattern from 2019 to 2023, with peak prevalence occurring during the winter and spring seasons. The evolutionary analysis of the HA genes shows that the strains from Xi′an in 2019 belong to the V1A.3 branch, and the strains from 2021 to 2023 belong to the V1A.3a.2 branch. Analysis of antigenic sites showed that there were variations in 6 sites of 3 antigenic determinants in the HA proteins of the BV strains from 2021-2022 compared to 2019, and 2 sites of 1 antigenic determinant changed in the HA proteins in 2023 compared to 2021-2022. The evolutionary analysis of the NA genes indicates that the BV strains from Xi′an in 2019 belong to the A. 1.1 branch. By 2021 and 2022, it had evolved into the A. 1.2 clade, and by 2023, it had further evolved into the B clade and its derivatives, with no strains showing mutations associated with resistance to NA inhibitors. Antigenic analysis indicated that the majority of BV strains in Xi′an were similar to the strains included in the vaccine composition. Furthermore, glycosylation analysis showed that the potential N-glycosylation sites in the HA proteins of BV strains from 2021-2023 were reduced by one compared to those from 2019, and only a few strains from 2023 displayed alterations in the potential N-glycosylation sites of the NA proteins.Conclusions:The HA and NA genes of the BV strains from 2019 to 2023 are continuously mutating and evolving into new branches. Since 2021, V1A.3a.2 has become the dominant evolutionary branch of the HA genes, while the evolutionary branches of the NA genes from 2019 to 2023 have been continuously changing.

Objective:Combined retrograde tracing with optogenetic methods,we are investigating the functional role of dorsal raphe nucleus(DRN)GABAergic neurons projecting to lateral habenula(LHb)terminals in anxiety-like behaviors.Methods:The specific retrograde tracing virus AAVretro-Ef1α-DIO-mCherry was injected into the LHb of Vgat-Cre mice.After the viral expression,Multi-brain slides scanning microscope imaging scan and observe the up-stream distribution of GABAergic neural projection in LHb.By retrograde tracing,opto-activated virus AAV2/9-Ef1a-DIO-ChR2-mCherry(ChR2 group)and control virus AAV2/9-Ef1a-DIO-mCherry(mCherry group)were injected into the DRN of Vgat-cre mice respectively.Three weeks after virus expression,DRNGABA neurons and the DRNCABA-LHb neural terminals were activated by optogenetic to observe their role in anxiety-like behaviors.Results:According to the results of retrograde tracing,the midbrain DRN is one of the major GABAergic neural projection brain areas in the LHb nucleus.Optogenetic stimulation of DRNGABA neurons,compared with the mCherry group,the ChR2 group showed sig-nificantly longer total moving distance,central area moving time and distance in the open field test(OFT);In the ele-vated plus maze(EPM),the open arm moving time and distance was significantly increased.When DRN GABA-LHb neural terminals were stimulated,compared with the mCherry group,the ChR2 group showed a significantly longer cen-tral zone moving time,distance and total moving distance in the OFT.During the elevated plus maze(EPM),the open arm moving time was significantly increased.Conclusion:The specific activation of the DRNGABA neuron as well as the DRNGABA-LHb neural projections showed that both significantly improved anxiety-like behaviors in mice.This provides new ideas and evidence for the treatment of anxiety,depression and other psychiatric disorders.

Objective:To investigate the role of GABAergic neurons in the bed nucleus of the stria terminalis (BNST) in isoflurane-induced general anesthesia-emergence in mice.Methods:Twenty-three healthy male Vgat-Cre transgenic mice, aged 8-10 weeks, weighing 22 g, were used in the study. In the immunofluorescence staining experiment, 8 mice were selected and divided into 2 groups ( n=4 each) using a random number table method: oxygen group and isoflurane group. Oxygen group inhaled oxygen at a rate of 1.0 L/min for 2 h, while isoflurane group inhaled 1.4% isoflurane + 1.0 L/min oxygen for 2 h. The animals were then sacrificed, and brain tissues were removed and subjected to immunofluorescence staining for determination of the expression of c-Fos and the rate of co-labeling with GABA neurons. For the optogenetic experiment, 15 mice were divided into 3 groups ( n=5 each) using a random number table method: control group (CON group), optogenetic excitation group (CHR2 group) and optogenetic inhibition group (eNpHR group). The rAAV-Ef1a-DIO-mCherry, rAAV-Ef1a-DIO-CHR2-mCherry, and rAAV-Ef1a-DIO-eNpHR3.0-mCherry viruses were injected to the BNST brain region. After 3 weeks of virus expression, the mice were exposed to 1.0% isoflurane + 1.0 L/min oxygen, and their cortical EEG was simultaneously monitored. When the mice reached a stable anesthetic state, optogenetic methods were utilized to modulate the viability of GABAergic neurons in the BNST brain region, and the burst suppression ratio (BSR) of the cortical EEG was recorded at 2 min before light stimulation and 2 min of light stimulation. Results:Compared with oxygen group, the rate of c-Fos co-labeling with GABA neurons in the BNST brain region was significantly reduced ( P<0.05), and the c-Fos-positive neurons were reduced in isoflurane group. Compared with CON group or with the prestimulation level, BSR was significantly decreased in CHR2 group ( P<0.001), and no significant change was found in BSR during light stimulation in eNpHR group ( P>0.05). Conclusions:Decreased viability of GABAergic neurons in the BNST brain region may be involved in the process of loss of consciousness in isoflurane-anesthetized mice, while increased viability of GABAergic neurons in the BNST brain region promotes the transition from anesthesia to emergence.