Based on the theory of "shaoyang（少阳） resembling the pivot" and collateral diseases， this article proposes that pulmonary fibrosis （PF） can be divided into three stages including wind bi （痹）， constraint bi， and atrophy bi. The core pathogenesis of PF is the obstruction of the pivot and pulmonary collateral obstruction. In terms of treatment， the basic principles are to harmonize and regulate the pivot， and to promote the circulation of the lung collaterals. Depending on the different characteristics of the "essence-attribute-function"， treatment methods such as harmonizing and regulating the pivot， resolving phlegm and removing stasis， supplementing deficiency and harmonizing collaterals are suggested. This approach ensures the regulation of the pivot， smooth circulation of qi and blood， unblocking of the lung collaterals and nourishing the lung body， achieving the goals of balancing the ascending and descending of qi， removing phlegm and stasis， and relieving cough and wheezing.

Objective:To compare the diagnostic efficacy of 18F-fibroblast activation protein inhibitor (FAPI)-42 PET/CT and 18F-FDG PET/CT for bone metastasis in patients with malignant tumors. Methods:From January 2022 to October 2023, the data of 238 patients (160 males, 78 females; age: 58(50, 66) years) with various malignant tumors who underwent both 18F-FAPI-42 and 18F-FDG PET/CT imaging at Nanfang Hospital, Southern Medical University were retrospectively reviewed. An abnormal focal radioactive uptake in bones on the PET images was considered as positive lesion for bone metastasis. The efficacy of 2imaging methods and the supplementary role of CT in the diagnosis of bone metastasis were evaluated by McNemar test. Results:Of 238 patients, 95 were with bone metastases and 143 were without bone metastases, including 436 lesions with bone metastases and 358 lesions without bone metastases. Based on the visual analysis, 18F-FAPI-42 PET showed a higher diagnostic sensitivity than 18F-FDG PET (98.4%(429/436) vs 86.5%(377/436); χ2=41.95, P<0.001), while 18F-FDG PET had a higher diagnostic specificity than 18F-FAPI-42 PET (83.2%(298/358) vs 70.4%(252/358); χ2=22.50, P<0.001), and the accuracies of both methods were similar (85.8%(681/794) vs 85.0%(675/794); χ2=0.16, P=0.685). However, when the positive lesions seen in PET were analyzed combined with the image features on CT by the same scanner, the diagnostic specificity of 18F-FAPI-42 PET/CT was significantly improved compared to that of 18F-FAPI-42 PET alone (91.3%(327/358) vs 70.4%(252/358); χ2=73.01, P<0.001), and was similar to 18F-FDG PET/CT (93.0%(333/358); χ2=0.78, P=0.377). Meanwhile, this combined analysis brought a higher sensitivity and accuracy of 18F-FAPI-42 PET/CT than 18F-FDG PET/CT in diagnosing bone metastases (sensitivity: 98.4%(429/436) vs 86.5%(377/436); χ2=41.95, P<0.001; accuracy: 95.2%(756/794) vs 89.4%(710/794); χ2=21.54, P<0.001). Conclusions:The diagnostic sensitivity of 18F-FAPI-42 PET for bone metastasis is superior to 18F-FDG PET, but the specificity is lower. However, when CT features is combined for analysis, the diagnostic specificity of 18F-FAPI-42 PET/CT is significantly improved, which thus can be used to diagnose bone metastasis accurately and is superior to 18F-FDG PET/CT.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Objective In this study,we investigated the correlation between the scores for different Liebowitz Social Anxiety Scale(LSAS)subscale models and the metabolic activity in specific regions of the brain using 18F-fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT)(18F-FDG PET),thereby improving the understanding of the neurobiological characteristics of social anxiety.Methods A total of 39 cognitively normal participants(29 men and 10 women,aged 30-63 years)were enrolled.All participants underwent LSAS assessment and brain 18F-FDG PET scanning.Correlations between metabolic activities in various brain regions and scores from the different LSAS subscales were analyzed accordingly.Results LSAS subscale scores were significantly correlated with metabolic activity in specific brain regions.In the Safren model,the score for the observation by others subscale was positively correlated with the left fusiform gyrus(P<0.001,false discovery rate[FDR]-corrected)and the left caudate tail(P<0.001,FDR-corrected),suggesting a close association between mood states related to observation by others and the metabolic activity in these regions.In the Baker model,the score for the eating and drinking subscale was negatively correlated with the right precuneus(P<0.001,FDR-corrected),while the score for the assertiveness subscale was positively correlated with the left caudate nucleus(P<0.001,FDR-corrected).These findings revealed the complex associative patterns between various mood and behavioral dimensions and metabolic activities in specific brain regions.Conclusion Social anxiety symptoms are closely associated with metabolic changes in specific brain regions,including the left insula,left caudate tail,and right precuneus.Moreover,different social situations activate distinct brain regions.Compared with individuals with social anxiety disorder,normal individuals exhibit involvement of fewer brain regions when experiencing social anxiety.These findings provide new experimental evidence for understanding the neural mechanisms underlying social anxiety.

γ-Aminobutyric acid(GABA),a pivotal inhibitory neurotransmitter in the central nervous system,plays an essential role in maintaining normal ocular physiological functions.GABA and its receptors are widely distributed through-out the retina,optic nerve,and visual pathways.Research indicates that GABA dysregulation is implicated in the pathogen-esis and progression of certain ophthalmic disorders.This article provides a comprehensive exploration of the relationship between GABA and ophthalmic diseases,including myopia,amblyopia,glaucoma,and dry eye syndrome.Moreover,the potential mechanisms and recent research advances are discussed.The findings may offer novel options and chances for the diagnosis and treatment of ophthalmic diseases.

Objective To observe the effects of electroacupuncture at the Hegu(LI4)acupoint on refractive parame-ters and the expression of tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1β)in the retinal tissue of mice with form-deprivation myopia(FDM).Methods Forty-eight SPF-grade,3-week-old healthy male C57BL/6J mice were ran-domly divided into four groups:normal control group,FDM group,sham acupuncture group,and Hegu group.Experimen-tal myopia was induced in the right eyes of mice in the latter three groups by wearing translucent diffuser goggles.Mice in the Hegu group received electroacupuncture stimulation at the Hegu(LI4)acupoint,while those in the sham acupuncture group received intervention with a non-penetrating blunt needle at the same location.Body weight,refractive error,and axial length were recorded for all mice before modeling and at 2 and 4 weeks after modeling.At 4 weeks post-modeling,mice were euthanized.Real-time quantitative PCR(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of TNF-α and IL-1β,respectively,in the right retinal tissues.Retinal cell apoptosis was assessed by TUNEL staining.Results At 2 weeks post-modeling,compared with the normal control group,the refractive error of the right eyes was significantly decreased and the axial length was significantly increased in the FDM,sham acupuncture,and Hegu groups(all P＜0.01).At 4 weeks post-modeling,compared with the normal control group,the refractive error was significantly decreased and the axial length was significantly increased in the FDM and sham acupuncture groups(all P＜0.001).Compared with both the FDM and sham acupuncture groups,the Hegu group showed a significant increase in re-fractive error and a significant decrease in axial length(all P＜0.001).At 4 weeks post-modeling,RT-qPCR and Western blot results showed that the mRNA and protein expression levels of TNF-α and IL-1 β in the retina were significantly higher in the FDM and sham acupuncture groups compared to the normal control group(all P＜0.05).In contrast,the protein ex-pression level of TNF-α and the relative mRNA and protein expression levels of IL-1β in the Hegu group were significantly lower than those in the FDM group(all P＜0.05).TUNEL staining results showed that the retinal cell apoptosis rate was significantly higher in the FDM and sham acupuncture groups compared to the normal control group(all P＜0.001).Com-pared with the FDM and sham acupuncture groups,the retinal cell apoptosis rate was significantly lower in the Hegu group(all P＜0.001).Conclusion Electroacupuncture at the Hegu(LI4)acupoint can significantly inhibit the progression of myopia in mice.The mechanism may be related to the downregulation of TNF-α and IL-1β expression in the retinal tissue,thereby inhibiting retinal cell apoptosis.

Objective: To systematically evaluate the influencing factors for autism spectrum disorder (ASD) in Chinese children, so as to provide the evidence for risk prediction and intervention of ASD. Methods: The publications pertaining to the influencing factors for ASD in Chinese children were retrieved from CNKI, Wanfang Data, VIP, PubMed and Embase database from inception to August 2024. A meta-analysis was performed using R package version 4.4.1. Sensitivity analysis was performed using the "leave-one-out" evaluation procedure. Publication bias was assessed using Egger regression test. Results: A total of 38 high-quality articles out of 9 015 articles were finally included, covering 149 607 individuals, with 5 974 cases of ASD. The meta-analysis showed that demographic factors including family history of related diseases (OR=14.958), maternal age of ≥35 years (OR=2.287) and parental history of hazardous occupations (OR=3.511); pregnancy-related factors including history of abortion (OR=5.832), no folate supplementation before and during pregnancy (OR=4.566), tobacco exposure before and during pregnancy (OR=2.596), history of other adverse exposures before and during pregnancy (OR=3.533), history of infectious diseases during pregnancy (OR=3.753), history of non-infectious diseases during pregnancy (OR=2.563), psychological problems during pregnancy (OR=3.864), history of medication during pregnancy (OR=6.651), adverse environmental exposures during pregnancy (OR=3.754), severe pregnancy reactions (OR=5.082), abnormal perinatal period (OR=2.987), cesarean delivery (OR=1.659), other perinatal adverse factors (OR=3.856), history of neonatal asphyxia (OR=2.792) and neonatal jaundice (OR=3.687); parenting factors including non-exclusive breastfeeding (OR=2.510), early/excessive screen exposure (OR=3.589) and feeding problems (OR=3.113); and individual factors including being male (OR=3.333) and history of convulsions/epilepsy (OR=7.035) were influencing factors for ASD in Chinese children. Conclusions The prevalence of ASD in Chinese children is primarily associated with 23 influencing factors, including family history of related diseases, history of abortion, no folate supplementation before and during pregnancy, medication during pregnancy, early/excessive screen exposure and history of convulsions/epilepsy.

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent