Osteoarthritis (OA) is a chronic degenerative joint disease and the most common type of arthritis. It involves almost any joint and can lead to chronic pain and disability. In the late 19th century, Roentgen discovered X-rays, and then began to use radiotherapy to treat tumors. In the 1980s, Luckey thought that low-level radiation (LDRT) might be beneficial to biology, and it was gradually applied to the treatment of some diseases. This paper introduces the epidemiology, risk factors, clinical manifestations and treatment methods of OA, points out that the cartilage injury and the important effect of synovial inflammation in the pathogenesis of OA, namely when the homeostasis of articular cartilage are destroyed, synthetic metabolism and catabolism imbalances, cartilage cells damaged their breakdown products consumed by synovial cells. Synovial cells and synovial macrophages secrete proinflammatory cytokines, metalloproteinases and proteolytic enzymes, leading to cartilage matrix degradation and chondrocyte damage, which aggravates synovial inflammation and cartilage damage, forming a vicious cycle. The possible mechanism and clinical research progress of LDRT in alleviating OA are discussed. LDRT can regulate inflammatory response, inhibit the production of pro-inflammatory cytokines, and promote the production of anti-inflammatory cytokines, thereby achieving anti-inflammatory effect. Studies have shown that after irradiation, the expression of inducible nitric oxide synthase (iNOS) was decreased, the release of reactive oxygen species (ROS) and the production of superoxide were inhibited, the anti-inflammatory phenotype of macrophages was differentiated from M1 to M2, the inflammatory CD8⁺ T cells were transformed into CD4⁺ T cells, and the number of dendritic cells (DC) was significantly reduced. LDRT inhibit the production of proinflammatory factors in leukocytes, reduce their recruitment and adhesion, and down-regulate the expression levels of cell adhesion molecules such as selectin, intercellular adhesion molecule (ICAM) and vascular endothelial cell adhesion molecule (VCAM). LDRT can regulate endothelial cells, stimulate endothelial cells to produce a large amount of TGF-β1, reduce the adhesion of endothelial cells to peripheral blood mononuclear cells (PBMC), and contribute to the anti-inflammatory effect of LDRT. It also exerted anti-inflammatory effects by regulating mitochondrial growth differentiation factor 15 (GDF15). After low-level radiation, the MMP-13 (matrix metalloproteinases-13) and the ADAMTS5 (recombinant a disintegrin and metalloproteinase with thrombospondin-5) decreased, the Col2a1 (collagen type 2) increased in chondrocytes. In the existing clinical studies, most patients can achieve relief of joint pain and recovery of joint mobility after irradiation, and the patients have good feedback on the efficacy. The adverse reactions (acute reactions and carcinogenic risks) caused by LDRT in the treatment of OA are also discussed. During the treatment of OA, a few patients have symptoms such as redness, dryness or itching at the joint skin, and the symptoms are mild and do not require further treatment. Patients are thus able to tolerate more frequent and longer doses of radiotherapy. In general, LDRT itself has the advantages of non-invasive, less adverse reactions, and shows the effect of pain relief and movement improvement in the treatment of OA. Therefore, LDRT has a broad application prospect in the treatment of OA.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Given the constraints imposed by the “14-day ethics” rule, numerous critical events occurring between the second and fourth weeks of embryonic development remain poorly understood. This underscores the necessity of a detailed understanding of embryonic development and regulation during this period, which is indispensable for preventing pregnancy failure, treating birth defects, and promoting human reproductive health.Rodents, characterized by their small size, rapid growth, strong reproductive capacity, and fully sequenced genomes, are widely used as crucial models for studying embryonic development. However, the substantial physiological differences between rodents and primates due to evolutionary divergence make it challenging to directly apply findings from rodent studies to primates. Besides, primates, our closest relatives in terms of evolutionary phylogenetics and physiological characteristics, share more than 95% genetic homology with humans, underscoring the urgent need for primate research. Furthermore, early-stage embryonic cells are both scarce and diverse, making their regulatory mechanisms and developmental pathways typically elucidated through single-cell sequencing. For instance, three significant articles published in Science in 2018 mapped the complete atlas of organ and tissue development from fertilization and captured dynamic gene expression profiles in zebrafish and frogs through single-cell transcriptomics. Unfortunately, relying solely on single-cell omics analysis falls short in effectively and comprehensively deciphering the intricate cellular network information. Single-cell multi-omics empower researchers to systematically decode cell heterogeneity and developmental trajectories at the individual cell level by combining transcriptomics, epigenomics, proteomics, and metabolomics analyses. These emerging technologies play a significant role in life sciences, enabling the elucidation of critical early primate embryonic development events from a multi-dimensional perspective, including zygotic genome activation (ZGA), X-chromosome dosage compensation, origins of primordial germ cells (PGCs), mechanisms of cell fate determination, and pivotal events in gastrulation and early organogenesis.This article chronicles the advancement of pivotal technologies, from single-cell histology to multi-omics, beginning with the single-cell transcriptome and culminating in a comprehensive analysis according to the central dogma of molecular biology. It highlights the transition from a singular to a holistic perspective in cellular analysis and reviews the application of multi-omics techniques in unveiling early primate embryonic development. Finally, it delves into the application of multi-omics technologies in enhancing our understanding of early primate embryonic development and explores future possibilities, directions, and challenges in this rapidly evolving field. In doing so, it emphasizes the critical role of interdisciplinary approaches, combining insights from genetics, molecular biology, and bioinformatics to foster innovations in reproductive medicine and developmental biology. The integration of such technologies offers the promise of breakthroughs in understanding complex biological processes, potentially leading to novel therapeutic strategies and advancements in reproductive health and medicine.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Patient 1,a 12-day-old female infant,presented with fever,cough,dyspnea,and elevated infection markers,requiring respiratory support.Metagenomic next-generation sequencing(mNGS)of blood and bronchoalveolar lavage fluid revealed Legionella pneumophila(LP),leading to diagnoses of LP pneumonia and LP sepsis.The patient was treated with erythromycin for 15 days and azithromycin for 5 days,resulting in recovery and discharge.Patient 2,an 11-day-old female infant,presented with dyspnea,fever,elevated infection markers,and multiple organ dysfunction,requiring mechanical ventilation.mNGS of blood and cerebrospinal fluid indicated LP,leading to diagnoses of LP pneumonia,LP sepsis,and LP intracranial infection.The patient was treated with erythromycin for 19 days and was discharged after recovery.Neonatal LP pneumonia lacks specific clinical symptoms,and azithromycin is the preferred antimicrobial agent.The use of mNGS can provide early and definitive diagnosis for severe neonatal pneumonia of unknown origin.

Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.
Humans ; Female ; HIV Infections ; Acquired Immunodeficiency Syndrome ; Infectious Disease Transmission, Vertical ; Nomograms ; Selenoproteins/genetics*

Pyroptosis is a novel process of programmed inflammatory necrosis, which is closely related to microbial infections and autoimmune diseases. In recent years it has been proved that Gasdermin D is an executive protein of pyroptosis. Cleaved Gasdermin D leads to the formation of pores in cell membrane to induce pyroptosis, and the release of inflammatory factors such as IL-1β and IL-18 aggravates the occurrence of inflammatory responses. With the deepening of Gasdermin D research, it is gradually clear its protein structure and activation sites, which has other activation pathways apart from inducing inflammasome activation. Activation of Gasdermin D does not necessarily mean cell death, even if it could induce the formation of pores in cell membrane and regulation of inflammatory cytokine secretion. These findings offer insight into Gasdermin D function and change our understanding of pyroptosis and programmed necrosis. The recent progress of Gasdermin D is highlighted in this review.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

AIM: To quantitatively evaluate the therapeutic efficacy of the asymmetric recession of bilateral lateral rectus in patients with unilateral type III Duane retraction syndrome.METHOD:Retrospective analysis of clinical data. The clinical data of 12 cases of type III Duane retraction syndrome with unilateral lateral rectus recession were analyzed. All subjects had restricted internal rotation, with narrowing of the palpebral fissure and vertical deviation, and restricted external rotation with widening of the palpebral fissure. All patients had abnormal head positions. The degree of strabismus was measured while maintaining the head in a neutral position. Asymmetric recession of bilateral lateral rectus was selected based on the degree of strabismus of affected eye or 1～3mm longer, with a smaller recession and Y-splitting in the affected eye and a larger recession in the healthy eye.RESULT:The difference in the degree of strabismus in the healthy eyes before and after surgery was statistically significant(Z=-4.158, P<0.01), as was the difference in the degree of restricted internal rotation(Z=-2.640, P=0.008). The difference in the degree of restricted external rotation was not statistically significant(Z=-1.732, P=0.083). The difference in abnormal head position was statistically significant(Z=-4.181, P<0.01), while the difference in eyeball recession was not statistically significant(Z=-1.414, P=0.157). The difference in vertical deviation was statistically significant(Z=-3.115, P=0.002). A total of 10 patients(83%)had stereoscopic vision before surgery, and 11 patients(92%)had recovered stereoscopic vision after surgery, with a further improvement in stereoacuity in 50% of patients.CONCLUSION:Asymmetric recession of bilateral lateral rectus combined with Y-splitting of the affected lateral rectus can effectively improve the degree of strabismus, abnormal head position, vertical deviation and stereoacuity without aggravating the degree of restriction of external rotation or eyeball recession.

Objective:To evaluate the diagnostic value and safety of transbronchial lung biopsy and bronchoalveolar lavage (BAL) in pulmonary complications in patients with hematological tumors.Methods:A retrospective analysis was performed on 68 patients with hematological tumors combined with lung lesions from The University of Hong Kong-Shenzhen Hospital and The Third People's Hospital of Shenzhen from May 2016 to May 2022, including 37 males, 31 females, with a median age of 56 years (age range 21-90 years), among which 20 patients were >65 years old. Diagnostic fiberoptic bronchoscopy was performed with signs including fever, cough, hypoxemia, hemoptysis, unexplained dyspnea, and imaging changes. Patients with pulmonary masses were evaluated for transbronchial lung biopsy, including inner and outer leaf mass and high-density shadow of lung leaves, pathological and special staining of biopsy tissue (Grocott staining), BAL acquisition of bronchoalveolar lavage fluid (BALF) for microbiological smear/culture, cytomegalovirus, Pneumocystis jirovecii and Mycobacterium tuberculosis (TB) smear, TB DNA, TB and fungal culture. Etiological analysis of pulmonary complications and observation of the complications associated with fiberoptic bronchoscopy in patients with hematological tumors were conducted. Results:BALF test was performed in all patients after bronchoscopy, bronchoscopic lung tissue biopsy was performed in 46 cases. The total number of confirmed pathogenic infections was 40, including 12 cases of fungal infections, 9 cases of bacterial infections (2 cases each of E. faecalis and Pseudomonas aeruginosa, 1 case of Staphylococcus aureus, 1 case of Klebsiella pneumoniae, 1 case of E. coli, 1 case of coagulase-negative Staphylococcus, and 1 case of Streptococcus mitis), 9 cases of viral infection (5 cases of cytomegalovirus, 3 cases of parainfluenza virus type Ⅲ, and 1 case of respiratory syncytial virus), 4 confirmed cases of Pneumocystis jirovecii pneumonia, 3 cases of suspected mixed infection of Pneumocystis jirovecii and fungi, 1 case of Cryptococcus, 2 cases of suspected TB infection. No pathogenic organisms were found in 28 cases, including 6 cases of mechanized pneumonia, 6 cases associated with a history of hematological tumors, and 16 cases of other unidentified pathogens. All patients did not experience death or other serious complications caused by bronchoscopy complications. Conclusion:Pulmonary complications are common in patients with hematological tumors, and the application of transbronchial lung biopsy has good safety. Early examination of fiberoptic bronchoscopy can provide pathogenic diagnostic evidence of bacterial, fungal, Pneumocystis jirovecii and viral infections, thus improving the diagnostic rate.