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.

ObjectiveBy exploring the influencing factors of readmission in patients with stable angina of coronary heart disease （CHD） based on real-world clinical data， to establish a risk prediction model of integrated traditional Chinese and western medicine， in order to provide a basis for early identification of high-risk populations and reducing readmission rates. MethodsA prospective clinical study was conducted involving patients with stable angina pectoris of CHD， who were divided into a training set and a validation set at a 7∶3 ratio. General information， traditional Chinese medicine （TCM）-related data， and laboratory test results were uniformly collected. After a one-year follow-up， patients were classified into a readmission group and a non-readmission group based on whether they were readmitted. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for readmission. A risk prediction model of integrated traditional Chinese and western medicine was constructed and visualized using a nomogram. The model was validated and evaluated in terms of discrimination， calibration， and clinical decision curve analysis. ResultsA total of 682 patients were included， with 477 in the training set and 205 in the validation set， among whom 89 patients were readmitted. Multivariate logistic regression analysis identified heart failure history ［OR = 6.93， 95% CI （1.58， 30.45）］， wiry pulse ［OR = 2.58， 95% CI （1.42， 4.72）］， weak pulse ［OR = 3.97， 95% CI （2.06， 7.67）］， teeth-marked tongue ［OR = 4.38， 95% CI （2.32， 8.27）］， blood stasis constitution ［OR = 2.17， 95% CI （1.06， 4.44）］， phlegm-stasis mutual syndrome ［OR = 3.64， 95% CI （1.87， 7.09）］， and elevated non-high-density lipoprotein cholesterol ［OR = 1.30， 95% CI （1.01， 1.69）］ as influencing factors of readmission. These factors were used as predictors to construct a nomogram-based risk prediction model for readmission in patients with stable angina. The model demonstrated moderate predictive capability， with an area under the receiver operating characteristic curve （AUC） of 0.818 ［95% CI （0.781， 0.852）］ in the training set and 0.816 ［95% CI （0.779， 0.850）］ in the validation set. The Hosmer-Lemeshow test showed good calibration （χ² = 4.55， P = 0.80）， and the model's predictive ability was stable. When the threshold probability exceeded 5%， the clinical net benefit of using the model to predict readmission risk was significantly higher than intervening in all patients. ConclusionHistory of heart failure， teeth-marked tongue， weak pulse， wiry pulse， phlegm-stasis mutual syndrome， blood stasis constitution， and non-high-density lipoprotein cholesterol are influencing factors for readmission in patients with stable angina of CHD. A clinical prediction model was developed based on these factors， which showed good discrimination， calibration， and clinical utility， providing a scientific basis for predicting readmission events in patients with stable angina.

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.

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.

Organ fibrosis is a chronic tissue injury caused by multiple causes,and the continuous dynamic progression will lead to abnormal organ structure and function.Recent studies have shown that Chinese materia medica can inhibit organ fibrosis by regulating the PI3K/Akt pathway,which holds potential significance for developing anti-fibrosis strategies.This article systematically reviewed the role of the PI3K/Akt signaling pathway in the entire process of fibrosis,and summarized the potential mechanisms of Chinese materia medica monomers,drug pairs and compounds that can target and intervene in PI3K/Akt signaling transduction in preventing and treating organ fibrosis,in order to provide reference for the intervention of Chinese materia medica in the PI3K/Akt pathway for the treatment of organ fibrosis.

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.

Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics* ; Printing, Three-Dimensional ; Needles ; Drug Delivery Systems/methods* ; Administration, Cutaneous ; Animals ; Microinjections/instrumentation* ; Skin Absorption ; Skin/metabolism*

Ovulatory disorders are mainly characterized by abnormal follicular maturation or ovulation， with complex etiologies and a lack of effective prevention and treatment methods. Autophagy dysfunction is closely related to the generation and progression of ovulatory disorders. This article systematically elucidates the mechanisms of TCM on follicular development and ovulatory disorders from the perspective of autophagy. It also reviews relevant studies on how TCM regulates autophagy to influence follicular development and improve ovulatory disorders. The findings reveal that TCM monomers/active ingredients （leonurine， total flavonoids from Eucommia ulmoides， alpinetin， icariin， etc.） and compound formulas （including Cangfu daotan decoction， Guishen yugong decoction， Zhuluan decoction， Yishen yangluan formula， Guishen pill， etc.） improve the follicular microenvironment， regulate sex hormone levels， and reduce follicular atresia by regulating autophagy-related genes and signaling pathways such as phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin and AMP-activated protein kinase. These actions thereby promote normal follicular development and ovulation， and delay ovarian aging. Most research in this field is based on cellular and animal experiments， often focusing on a single signaling pathway or factor. Some studies fail to fully reflect the individualized treatment characteristics of TCM that emphasize “syndrome differentiation and treatment”， highlighting the urgent need for further investigation.

Malignant pleural effusion(MPE)is a common complication in patients with advanced malignant tumors,which not only significantly reduces their quality of life but also shortens their survival duration.Despite the widespread use of traditional treatment methods such as thoracentesis and pleurodesis,their efficacy is limited accompanied by high recurrence rates.Therefore,exploring novel therapeutic strategies becomes particularly urgent.In recent years,immunotherapy has attracted extensive attention for its potential in cancer treatment.This article systematically reviews the roles of CD4+T cell subsets,including regulatory T cells(Treg),T helper cell(Th)17,Th9,and Th22 cells,within the immunosuppressive microenvironment of MPE.These cell subsets are involved in the formation of the immunosuppressive state of MPE through various mechanisms and play key roles in the occurrence and development of the disease.In addition,the article discusses in detail the role of immune checkpoint molecules,such as programmed death protein 1(PD-1),PD-1 ligand(PD-L1),and cytotoxic T-lymphocyte-associated protein 4(CTLA-4),in the immune evasion of MPE.The abnormal expressions of these molecules provide opportunity for tumor cells to evade immune system surveillance.At the same time,this article also summarizes the application prospects of novel immunotherapy strategies,such as adoptive cell therapy(ACT)and chimeric antigen receptor T cell(CAR-T)therapy,in the treatment of MPE.These innovative therapies offer possibilities for improving the prognosis of MPE patients through activating and enhancing the anti-tumor immune response.