Cerebral small vessel disease (CSVD) is an important cause of stroke and cognitive impairment, with complex pathogenesis and limited therapeutic options. Although monogenic hereditary CSVD has a low incidence, its well-defined causative genes provide a unique " natural model" for revealing the core molecular pathways of CSVD. Based on previous studys, this article systematically sorts out the newly identified pathogenic genes of monogenic CSVD, such as NIT1, MAP3K6 and ARHGEF15, and precisely identifies core pathophysiological processes including vascular smooth muscle cell dysfunction and extracellular matrix homeostasis imbalance. Furthermore, it reviews the latest advances in genome-wide association studies (GWAS) on sporadic CSVD and its imaging markers, and confirms an overlap in their genetic architectures. Finally, this article discusses the research strategy of integrating multi-omics data such as transcriptomics and proteomics to deeply analyze the biological mechanisms of risk variants, and summarizes the clinical translational value of genetic research in the precision diagnosis, risk stratification, drug target mining and drug repositioning of CSVD.

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

OBJECTIVE: To investigate the therapeutic effect of the short-penis treatment apparatus and wide-band infrared therapy apparatus on penile dysplasia (PDP) in children and establish objective parameters for assessing the severity of PDP. METHODS: This study included 252 children received in the Department of pediatric urology of the First Affiliated Hospital of Xinjiang Medical University from January to December 2023, 102 with PDP (the PDP group) and the other 150 with normal penile development (the control group), those of the former group treated with the short-penis therapeutic apparatus and wide-band infrared therapy apparatus. Before and after 30 days of treatment, we measured the flaccid penile length (FPL), stretched penile length (SPL) and penile diameters (PD) of the children, and defined the penile dysplasia index as the FPL/SPL and FPL/PD ratios. RESULTS: The penile parameters exhibited statistically significant differences between the PDP and control groups, (FPL:［1.97±0.72］cm vs ［3.25±0.51］ cm, P<0.01; SPL:［3.80±0.81］cm vs ［5.21±0.79］cm,P<0.01).The FPL remarkably increased in the PDP group after treatment(［1.97±0.72］cm vs ［2.90±1.20］ cm, P<0.01). Both FPL and SPL were notably shorter in the PDP cases than in the controls, with the cutoff values of 0.57 and 2.09, sensitivities of 80.7% and 95.3%, and specificities of 69.6% and 82.4% for FPL/SPL and FPL/PD, respectively. CONCLUSION The short-penis therapeutic apparatus and wide-band infrared therapy apparatus can promote the growth and development of the penis in children. The ratio of FPL/PD can serve as an objective indicator to effectively describe the severity of penile developmental abnormalities.
Humans ; Male ; Penis/abnormalities* ; Child ; Penile Diseases/therapy* ; Child, Preschool ; Infant

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Objective To quantitatively compare the dosimetric differences among 4 volumetric modulated arc therapy(VMAT)plans by analyzing the number of arcs and collimator angle settings,aiming to establish a standardized planning template for hippocampal-sparing prophylactic cranial irradiation(HS-PCI)in clinic and improve both planning quality and clinical efficiency.Methods Twenty HS-PCI patients were enrolled,with 4 VMAT plans(V2c,V2p,V3,and V4)for each patient.The differences in target dose,organs-at-risk dose,and monitor units were compared.Results V4 plan had the highest PTV D98%and V95%,and the differences of PTV D98%in V2c vs V2p,V2c vs V4,and PTV V95%in V2c vs V4 were statistically significant(P<0.05).Meanwhile,V4 plan had the lowest PTV Dmax and Dmin doses.Specifically,statistically significant differences were observed in PTV Dmax in V4 vs V2c,V4 vs V2p,V4 vs V3,as well as PTV Dmin in V2c vs V2p,V2c vs V3,V2c vs V4,V2p vs V4(P<0.05).The PTV Dmean was the highest in V2p plan,with statistically significant differences observed in V2c vs V2p,V2c vs V4,V2p vs V3,and V3 vs V4(P<0.05).The highest PTV D2%dose was observed in V2p plan,and the differences in V2c vs V2p,V2c vs V4,V2p vs V3,V3 vs V4 were statistically significant(P<0.05).The homogeneity index and conformity index were close in 4 plans(P=0.946,P=0.380).V4 plan had the lowest Dmax,Dmean,and Dmin of the hippocampus,with significant differences in hippocampal Dmax in V4 vs V2c,V4 vs V2p,hippocampal Dmean in V4 vs V2c,V4 vs V2p,V3 vs V2c,and hippocampal Dmin in V2c vs V2p/V3/V4,and V4 vs V2p(P<0.05).V3 plan had the lowest Dmax for bilateral lenses,and V4 plan showed the lowest Dmax for lenses with a 3 mm expansion,with significant differences between V2c and V2p/V3/V4(P<0.05).V4 plan had the lowest dose for the right optic nerve,with significant differences in V4 vs V2p,and V4 vs V3(P<0.05).No significant differences were observed for the left optic nerve and optic chiasm.The monitor units in V2p plan was the lowest.Conclusion When differences in organs-at-risk doses and plan quality parameters are insignificant,V2p plan is recommended as it can ensure treatment quality while reducing delivery time.

Objective To observe the origin and course of the obturator artery(OA),so as to provide anatomical reference for reducing hemorrhage during pelvic surgery and pubic fracture fixation.Methods A total of 65 human hemi-pelvises specimens with intact structure were dissected to observe the origin,course and other variations of OA.Measure the length of the inner section of OA basin and the outer diameter at the origin,etc.Results OA originated from the internal iliac artery in 57 cases(87.7%),including 3 cases(4.6%)of the superior gluteal artery,5 cases(7.7%)of the inferior gluteal artery,3 cases(4.6%)of the external iliac artery and 5 cases(7.7%)of the inferior epigastric artery.OA participated in the formation of the arterial trunk in 3 cases(4.6%).The length of the pelvic segment of the OA in male and female was(50.87±15.41)mm and(51.71±14.19)mm,respectively,with no statistically significant difference between them(P>0.05).The outer diameters at the origin of the OA in male and female were(2.79±1.05)mm and(2.35±0.86)mm,and there was no statistically significant difference between them(P>0.05).Conclusion OA mainly originated from the anterior trunk of the internal iliac artery,with a few OA originated from the branches of the posterior trunk or the inferior epigastric artery,or participated in the formation of the arterial trunk.In pelvic surgery involving OA area,attention should be paid to the length of its pelvic segment and the outer diameter at the origin of OA,so as to better locate and protect blood vessels during surgery.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

This study aimed to investigate the effects of caffeoylquinic acids from Erigeron breviscapus(EBCQA) on cognitive impairment and mitochondrial dysfunction in Alzheimer's disease(AD), and to explore its underlying mechanisms. The impacts of EBCQA on paralysis, β-amyloid(Aβ) oligomerization, and mRNA expression of mitophagy-related genes [PTEN-induced putative kinase 1(PINK1) homolog-encoding gene pink-1, Parkin homolog-encoding gene pdr-1, Bcl-2 interacting coiled-coil protein 1(Beclin 1) homolog-encoding gene bec-1, microtubule-associated protein 1 light chain 3(LC3) homolog-encoding gene lgg-1, autophagic adapter protein 62(p62) homolog-encoding gene sqst-1] were examined in the AD Caenorhabditis elegans CL4176 model, along with mitochondrial functions including adenosine triphosphate(ATP) content, enzyme activities of mitochondrial respiratory chain complexes Ⅰ,Ⅲ, and Ⅳ, and mitochondrial membrane potential. Additionally, the effects of EBCQA on the green fluorescent protein(GFP)/red fluorescent protein from Discosoma sp.(DsRed) ratio, the expression of phosphatidylethanolamine-modified and GFP-labeled LGG-1(PE-GFP::LGG-1)/GFP-labeled LGG-1(GFP::LGG-1), and GFP-labeled SQST-1(GFP::SQST-1) proteins were investigated in transgenic C. elegans strains. The effect of EBCQA on paralysis was further evaluated after RNA interference(RNAi)-mediated suppression of the pink-1 and pdr-1 genes in CL4176 strain. An AD rat model was established through intraperitoneal injection of D-galactose and intragastric administration of aluminum trichloride. The effects of β-nicotinamide mononucleotide(NMN) and EBCQA on learning and memory ability, neuronal morphology, mitophagy occurrence, mitophagy-related protein expression(PINK1, Parkin, Beclin 1, LC3-Ⅱ/LC3-Ⅰ, p62), and mitochondrial functions(ATP content; enzyme activities of mitochondrial respiratory chain complexes Ⅰ, Ⅲ, and Ⅳ; mitochondrial membrane potential) were investigated in this AD rat model. The results showed that EBCQA delayed paralysis onset in the CL4176 strain, reduced Aβ oligomer formation, and upregulated the mRNA expression levels of lgg-1, bec-1, pink-1, and pdr-1, while downregulating sqst-1 mRNA expression. EBCQA also enhanced ATP content, mitochondrial membrane potential, and the activities of mitochondrial respiratory chain complexes Ⅰ, Ⅲ, and Ⅳ. Furthermore, EBCQA improved the PE-GFP::LGG-1/GFP::LGG-1 ratio, reduced GFP::SQST-1 expression, and decreased the GFP/DsRed ratio. Notably, the ability of EBCQA to delay paralysis was significantly reduced following RNAi-mediated suppression of pink-1 and pdr-1 in CL4176 strain. In AD rats, the administration of NMN or EBCQA significantly improved learning and memory, restored neuronal morphology in the hippocampus, increased autophagosome numbers, and upregulated the expression of PINK1, Parkin, Beclin 1, and the LC3-Ⅱ/LC3-Ⅰ ratio, while reducing p62 expression. Additionally, the treatment with NMN or EBCQA both elevated ATP content, mitochondrial respiratory chain complex Ⅰ, Ⅲ, and Ⅳ activities, and mitochondrial membrane potential in the hippocampus. The above findings indicate that EBCQA improves cognitive impairment and mitochondrial dysfunction in AD, possibly through activation of PINK1/Parkin-mediated mitophagy.
Animals ; Alzheimer Disease/psychology* ; Mitophagy/drug effects* ; Mitochondria/genetics* ; Caenorhabditis elegans/metabolism* ; Ubiquitin-Protein Ligases/genetics* ; Cognitive Dysfunction/physiopathology* ; Rats ; Protein Kinases/genetics* ; Humans ; Male ; Disease Models, Animal ; Caenorhabditis elegans Proteins/genetics* ; Drugs, Chinese Herbal/administration & dosage*