To summarize the clinical experience of treating idiopathic olfactory disorder from the perspective of heart and lungs. It is believed that the sense of olfaction is based on the nose， rooted in the heart， functioning through the lungs， and conveyed by pectoral qi. The key pathogenesis of idiopathic olfactory disorder lies in the accumulation of pathogenic factors in the heart and lungs， blood vessel obstruction， the failure of the lungs to disperse and descend， and the loss of control of pectoral qi. In treatment， internal and external therapies could be combined. The internal therapy can correct the imbalance of the zang-fu organs， using the self-prescribed Bilong Formula （鼻聋方） to dispel wind and diffuse the lung， invigorate blood and relieving stuffy orifices； the external therapy can clear nasal obstruction， supplemented by intradermal needle embedding at three acupoints， bilateral Yingxiang （LI 20）， bilateral Shangyingxiang （EX-HN 8） and Yintang （GV 29）， and integrated olfactory training for comprehensive treatment.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Objective:To explore the possible mechanism of cognitive impairment in aged mice induced by sevoflurane and the role of the AMPK/GSK-3β/Nrf2 signaling pathway.Methods:Eighteen 16-month-old SPF male C57BL/6J mice were randomly assigned to either a control group or a sevoflurane group according to the random number table method( n=9 per group). Mice in the sevoflurane group were exposed to 3% sevoflurane for 2 h every day for three consecutive days.Cognitive function of mice was assessed by novel object recognition test and Morris water maze test.Golgi staining was used to analyze dendritic spine morphology and density in the hippocampus. Mitochondrial ultrastructure was examined by transmission electron microscopy. Oxidative stress in hippocampal tissue was evaluated by reactive oxygen species(ROS) and glutathione(GSH) assay kits. Western blot was performed to measure synaptic plasticity-related proteins and proteins involved in the AMPK/GSK-3β/Nrf2 signaling pathway, while Nrf2 expression was assessed by immunofluorescence. Statistical analysis was performed using GraphPad Prism 7 software with independent-samples t-test or Mann-Whitney U test for between-group comparisons. Results:(1) The novel object recognition test showed that the recognition index in the sevoflurane group was significantly lower than that in the control group ( Z=-3.256, P=0.001).The escape latency in the Morris water maze test was longer ((49.50±10.14) s, (18.62±6.59) s; t=-7.221, P<0.001) and the number of platform crossings was lower ( Z=-2.673, P=0.008) in the sevoflurane group compared with those of the control group. (2) Results from Western blot and Golgi staining showed that the expression levels of hippocampal synapse-related proteins in the sevoflurane group, including PSD95 ((0.38±0.07), (1.00±0.21); t=4.885) and SYN1 ((0.30±0.10), (1.00±0.10); t=8.575), were lower than those in the control group, as well as the number of dendritic spines ((10.3±2.5), (20.0±1.0); t=6.183)(all P<0.05). (3) Transmission electron microscopy showed mitochondrial damage in the hippocampus of the sevoflurane group, and the expression level of ROS ((3.05±0.90), (0.97±0.16); t=-4.555, P=0.004) was significantly higher than that of the control group, while the expression level of GSH ((0.71±0.07), (1.00±0.09); t=5.396, P=0.002) was significantly lower than that of the control group.(4) Western blot and immunofluorescence demonstrated that hippocampal p-AMPK, p-GSK-3β (Ser9), and HO-1 expression levels in the sevoflurane group were significantly lower than those in the control group ( t=2.845, 7.087, 4.551, all P<0.05), and Nrf2 fluorescence intensity was also markedly reduced ( P<0.05). Conclusion:The cognitive impairment induced by sevoflurane in aged mice may be caused by mitochondrial damage, oxidative stress response and synaptic damage, which maybe associated with the inhibition of the AMPK/GSK-3β/Nrf2 signaling pathway.

Objective To investigate the effects of galectin-3(Gal3)on autophagy in high glucose-induced human telomerase reverse transcriptase-immortalized retinal pigment epithelial(hTERT-RPE)cells.Methods The hTERT-RPE cells cultured in vitro were randomly divided into a normal group(group C),a high glucose group(group HG),a high glu-cose+si-NC group(group HG+si-NC)and a high glucose+si-Gal3 group(group HG+si-Gal3).Reverse transcrip-tion polymerase chain reaction(RT-PCR)was used to detect the relative mRNA expression levels of Gal3,intercellular ad-hesion molecule(ICAM)-1,interleukin(IL)-6 and tumor necrosis factor(TNF)-α in hTERT-RPE cells of each group.The expression levels of IL-1 and IL-6 in the supernatant of hTERT-RPE cells were measured by enzyme-linked immunosorbent assay(ELISA).The expression level of reactive oxygen species(ROS),the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in hTERT-RPE cells were analyzed by dichlorofluorescin diacetate(DCFH-DA)staining,the colorimetric method and the microplate method,respectively.The protein expression levels of Gal3,the ratio of microtubule associated protein 1 light chain 3(LC3)type Ⅱ to type Ⅰ(LC3 Ⅱ/LC3 Ⅰ),Beclin 1,and autophagy-associat-ed 5(ATG5)and 7(ATG7)in hTERT-RPE cells from each group were detected by Western blot analysis.After the hTERT-RPE cells in each group were transfected with double fluorescent mRFP-GFP-LC3 plasmids alone and with RFP-LAMP1 and GFP-LC3 plasmids jointly,the changes of autophagy flow in hTERT-RPE cells were detected by laser confocal microscopy.Results Compared with the group C,the group HG showed an increase in the expression of Gal3,IL-1,IL-6,TNF-α,ICAM-1,P62,ROS and MDA content(all P＜0.05).However,the expression of LC3 Ⅱ/LC3 Ⅰ,Beclin1,ATG7,ATG5,the SOD activity,and the number of red(autolysosomes)and yellow fluorescence spots(autophagosomes)of the double fluo-rescent mRFP-GFP-LC3 plasmid were all lower in the group HG than those in the group C(all P＜0.05).There was no sig-nificant difference in the number of yellow fluorescent spots(autolysosomes)co-located by RFP-LAMP1 and GFP-LC3 plas-mids between groups C and HG(P＞0.05).There were no significant differences in the expression levels of the above-mentioned indexes in hTERT-RPE cells between groups HG and HG+si-NC(all P＞0.05).The expression levels of Gal3,IL-1,IL-6,TNF-α,ICAM-1,P62,ROS and MDA content in hTERT-RPE cells of the group HG+si-Gal3 were lower than those of the group HG+si-NC(all P＜0.05).Compared with those in the group HG+si-NC,the expression levels of LC3 Ⅱ/LC3 Ⅰ,Beclin1,ATG7,ATG5,SOD activity,and the number of red and yellow fluorescent spots of the double fluo-rescent mRFP-GFP-LC3 plasmid were increased in the group HG+si-Gal3(all P＜0.05).There was no significant differ-ence in the number of yellow fluorescent spots co-located by RFP-LAMP1 and GFP-LC3 plasmids between groups HG+si-GaL3 and HG+si-NC(P＞0.05).Conclusion Gal3 is significantly elevated in hTERT-RPE cells induced by high glu-cose,resulting in impaired autophagy flow.It produces a direct regulatory effect on the formation of autophagosomes,and plays a highly active role in oxidative damage and expression of inflammatory factors in hTERT-RPE cells induced by high glucose.

Retinitis pigmentosa (RP) is a kind of ophthalmic hereditary disease characterized by degenerative dystrophy of photoreceptors in the retina.It is one of the main causes of hereditary visual impairment and blindness. USH2A gene is the primary pathogenic gene of both syndromic RP (e.g., Usher syndrome type Ⅱ, USH2) and non-syndromic RP, so elucidating its function and pathogenesis is of important theoretical significance and clinical application value.However, due to the wide range of USH2A gene variations, as well as USH2A protein has huge molecular weight and complex protein structure, the molecular pathogenesis of RP caused by USH2A variations remains unknown, which has hindered the progress of gene therapy and also poses many challenges to researchers and clinicians.Recently, with the development of gene editing technology and the establishment of animal models, the function of USH2A gene has been further studied.For example, USH2A is involved in cell adhesion at retinal basal membrane.USH2A interacts with other USH proteins to maintain photoreceptor structure and plasticity.USH2A can participate in vesicle transport from the inner segment to the outer segment of photoreceptors.USH2A maintains the normal function of photoreceptor cells by regulating autophagy.This article reviews the pathogenesis of RP induced by variations of USH2A gene.

The incidence of food allergy is on the rise, with the capacity to impact various organ systems, including but not limited to the skin, respiratory system, gastrointestinal system, cardiovascular system, and nervous system.In extreme cases, these allergies can result in anaphylaxis.Immunoglobulin E (IgE)-mediated type Ⅰ hypersensitivity reactions are a common cause of food allergy and are the primary pathway to anaphylaxis.Omalizumab, the first biologic therapy approved for the treatment of IgE-mediated food allergy, can be incorporated into a comprehensive management strategy for food allergy sufferers.However, due to the lack of definitive evidence, the safety and efficacy of Omalizumab in all patients with IgE-mediated food allergy remain equivocal.In light of this, Global Allergy and Asthma European Network Anaphylaxis Centres of Reference and Excellence convened a panel of experts to deliberate on the appropriate patient and therapeutic strategies for Omalizumab, culminating in a consensus statement.This paper aimed to interpret the consensus proposed by the experts, with the objective of assisting clinicians in better understanding the application of Omazumab in patients with IgE-mediated food allergy.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective To investigate the abnormal changes characteristics of the degree centrality(DC)of the brain functional network in patients with benign paroxysmal positional vertigo(BPPV)in the classical frequency band(0.010-0.080 Hz),the slow-4 frequency band(0.027-0.073 Hz),and the slow-5 frequency band(0.010-0.027 Hz).Methods Twenty patients with BPPV(BPPV group)and 14 healthy controls(HC)(HC group)were selected.Resting-state functional magnetic resonance imaging(rs-fMRI)scans were performed,and the clinical data were analyzed.The DC method was used to analyze the changes of centrality of resting state network in patients with BPPV.Results Compared with the HC group,the BPPV group showed an increase in DC in the left caudate nucleus in the classical frequency band(P＜0.05),and a decrease in DC in the right auxiliary motor region in the classical frequency band(P＜0.05);within the slow-4 frequency band,no significant differences were observed in brain regions(P＞0.05);within the slow-5 frequency band,the BPPV group showed an increase in DC in the left thalamus(P＜0.05),while the left anterior cingulate and paracingulate gyrus showed a decrease in DC(P＜0.05).Conclusion Patients with BPPV have spontaneous activity disorders in multiple brain regions at resting states,and these changes show frequency band specificity.

Objective To explore the impact of ten-eleven translocation 2(TET2)mutations on imiquimod(IMQ)-induced psoriatic skin inflammation using a TET2-knockout(TET2-/-)mouse model.Methods Mice were divided randomly into a wild-type(WT)vaseline group,WT imiquimod group,TET2-/-vaseline group,and TET2-/-imiquimod group.IMQ was used to establish a psoriasis-like dermatitis model,and the degree of skin lesions and pathological changes in mice in the WT imiquimod and TET2-/-imiquimod groups were observed and compared daily during the modeling period.The mice were sacrificed when the phenotype had reached the peak and the spleen index was recorded in each group.Gene expression levels of the inflammatory factors tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-17A,and IL-23 in mouse back lesions were detected by quantitative reverse transcription polymerase chain reaction.Skin histopathology was compared in hematoxylin/eosin-stained sections.IL-17,interferon(INF)-γ,and TNF-α protein expression levels in the back skin of mice in the four groups were detected by immunohistochemistry.The ultrastructure of the dermis and epidermis was observed using transmission electron microscopy.Results TET2 expression was down-regulated in skin lesions in WT imiquimod group.Dermatitis lesions were more severe and progressed faster in TET2-/-imiquimod group compared with WT imiquimod group,and the psoriasis area and severity index score and spleen index were both higher.mRNA expression levels of TNF-α,IL-6,IL-17A,and IL-23 in skin lesions were higher and epidermal thickening and inflammatory cell infiltration were increased,and protein expression levels of IL-17,INF-γ,and TNF-α were significantly higher in skin lesions in TET2-/-imiquimod group compared with WT imiquimod group.In addition,cell junctions were absent in skin lesions in TET2-/-imiquimod group and mitochondrial ridges were broken and dissolved,mitochondrial vacuoles were present,and the texture of the mitochondrial membrane was darker.Conclusions Loss of TET2 promotes the inflammatory response and exacerbates IMQ-induced psoriasis-like dermatitis injury in mice.

Objective To investigate the abnormal changes characteristics of the degree centrality(DC)of the brain functional network in patients with benign paroxysmal positional vertigo(BPPV)in the classical frequency band(0.010-0.080 Hz),the slow-4 frequency band(0.027-0.073 Hz),and the slow-5 frequency band(0.010-0.027 Hz).Methods Twenty patients with BPPV(BPPV group)and 14 healthy controls(HC)(HC group)were selected.Resting-state functional magnetic resonance imaging(rs-fMRI)scans were performed,and the clinical data were analyzed.The DC method was used to analyze the changes of centrality of resting state network in patients with BPPV.Results Compared with the HC group,the BPPV group showed an increase in DC in the left caudate nucleus in the classical frequency band(P＜0.05),and a decrease in DC in the right auxiliary motor region in the classical frequency band(P＜0.05);within the slow-4 frequency band,no significant differences were observed in brain regions(P＞0.05);within the slow-5 frequency band,the BPPV group showed an increase in DC in the left thalamus(P＜0.05),while the left anterior cingulate and paracingulate gyrus showed a decrease in DC(P＜0.05).Conclusion Patients with BPPV have spontaneous activity disorders in multiple brain regions at resting states,and these changes show frequency band specificity.