The disease spectrum of ABCB4 gene mutation involves various diseases such as progressive familial intrahepatic cholestasis type 3 （PFIC3）， gallstone disease， intrahepatic cholestasis of pregnancy， portal hypertension， liver cirrhosis， and even primary hepatic and biliary malignancies. A young male patient was admitted to Department of Hepatobiliary Medicine， Eastern Hepatobiliary Surgery Hospital， and was initially diagnosed with liver cirrhosis and gallstones， and he was planned to receive laparoscopic cholecystectomy. Preoperative examination showed abnormal liver function， liver cirrhosis， splenomegaly， and mild esophageal varices， and next-generation sequencing was performed to make a confirmed diagnosis of ABCB4 gene mutation-associated liver cirrhosis with gallstones. The liver function of the patient gradually returned to normal after cholagogic treatment with ursodeoxycholic acid capsules.

Objective To observe the influence of different energy windows of the medium-energy general-purpose(MEGP)collimator on image quality,so as to optimize the energy window of yttrium-90(90Y)bremsstrahlung SPECT imaging.Methods 90Y bremsstrahlung spectrum was acquired,and the sensitivity,percentage of the source counts in useful field of view(S/FOV%)and signal-to-background ratio(S/B)of 90Y bremsstrahlung SPECT imaging at MEGP under different energy windows were compared.Results The energy spectrum of 90Y bremsstrahlung was a continuous curve,with the peak of 76.2 keV with MEGP collimator.The images obtained with MEGP collimator were clear,and no significant differences of S/FOV%nor S/B was found between 10%and 20%window width groups(both P＞0.05),but the sensitivities of the latter was higher than the former(P＜0.05).The sensitivity of 70-90 keV images was relatively high,while the S/FOV%and S/B had decreased.The S/FOV%and S/B of images ranging from 40-60 keV were high,but the sensitivity was low.Images acquired with 100 keV±20%showed fairly high sensitivity,S/FOV%and S/B,which was 69.73%,0.62 and 1.64,respectively.Conclusion When performing 90Y bremsstrahlung SPECT with MEGP collimator,the image quality at 20%window width was better than at 10%window width,and 100 keV±20%showed fairly high sensitivity and not significantly decreased S/FOV%and S/B.

Objective:On the basis of summarizing the previous studies on the access and pricing strategies of multi-indication drugs,based on the actual situation in China,it develops the access and pricing strategies of multi-indication drugs applicable to the adjustment mechanism of China's health insurance catalog and carry out feasibility analysis,with a view to providing methodological support for the national health insurance department in the adjustment of the health insurance catalog in the future.Methods:First,through literature review and expert survey,it sorts out the medical insurance access and pricing strategies for multi-indication drugs that may be applicable in China.Secondly,a feasibility evaluation framework for National Drug Insurance List(NRDL)access and pricing strategies for multi-indication drugs is constructed through literature review,and various stakeholders in the NRDL process are invited to conduct feasibility scores based on the questionnaire.In addition,9 pathways are identified through expert research,and various stakeholders in NRDL process are invited to conduct path analysis based on questionnaires.Finally,relevant recommendations are formed based on the research results.Results:According to the results of the feasibility evaluation the direct access is less feasi-ble,while negotiated access and simplified negotiated access are comparable;pricing by weighted average was less feasible,pricing by primary indication and pricing by minimum value are comparable.The results of the pathway analysis show that differences in health insurance access and pricing strategies for selecting drugs with multiple indications under different pathways.Conclusion:It is needed to refine the medical insurance access and price calculation methods for drugs with multiple indications;improve the database construction to support refined calculation of medical insurance;and actively explore the innovative payment methods for medical insurance with multiple indications.

BACKGROUND:Heart rate variability biofeedback is a respiratory training method that uses slow and deep breathing at the resonant frequency to induce rhythmic,high-amplitude oscillations in the cardiovascular system,thereby stimulating and exercising the autonomic and baroreflex.However,current studies have not systematically reviewed how heart rate variability biofeedback modulates the autonomic function and produces effects.There is a lack of public understanding of the mechanism of heart rate variability biofeedback,and its application progress and scheme are not fully understood. OBJECTIVE:To review the existing experimental studies on the effects of heart rate variability biofeedback on symptoms in different populations at home and abroad and to introduce the mechanisms and advances in the application of heart rate variability biofeedback to modulate the autonomic nervous system. METHODS:"Heart rate variability biofeedback,resonance breathing,heart rate variability,autonomic nerve,breathing training,chronic diseases,mental illness,biofeedback"were used as Chinese or English keywords to search in CNKI,WanFang Database,PubMed,and Web of Science.A total of 72 core related papers were included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The body's oscillation system and resonance system are essential for the effectiveness of heart rate variability biofeedback.Oscillations reflect the response to external stimuli and self-regulating reflex systems,while resonances involve synchronous oscillations that result in higher amplitude operations.The balance between sympathetic and parasympathetic nerves is crucial for maintaining a stable internal environment.Autonomic nervous system disorders are associated with reduced heart rate variability and are closely linked to the progression of related diseases.Heart rate variability biofeedback utilizes the resonance characteristics of the cardiovascular system,inducing rhythmic high-amplitude oscillations by employing deep slow breathing at the resonance frequency.This method improves the regulatory function of the sympathetic and parasympathetic system reflexes and enhances the balance regulation between the two systems.Two major mechanisms of cardiovascular system resonance are the baroreflex closed-loop pathway and respiratory sinus arrhythmia.These mechanisms,along with the unique delay of baroreflex,result in a 0° phase angle oscillation between heart rate and respiration and a 180° phase angle oscillation between blood pressure and respiration during breathing at the resonant frequency rhythm.Periodically stimulating the human cardiovascular oscillation system through this method is an easy-to-operate and effective training approach.Currently,heart rate variability biofeedback is mainly applied in the fields of mental illness,chronic disease,and sports.However,the intervention mechanism and efficacy are unclear,the intervention content,frequency and duration are varied,and there are limited review studies on the intervention methods tailored to different types of individuals.As a non-drug and non-invasive intervention,heart rate variability biofeedback can significantly increase heart rate variability,regulate the balance between sympathetic and parasympathetic nerves,and improve the stability and adaptability of the autonomic nervous system.In the future,it is suggested to investigate the mechanisms and potential applications of the pathways of the heart rate variability biofeedback that induce cardiovascular resonance.It is also recommended to incorporate long-term follow-ups to assess the sustained value of heart rate variability biofeedback in various fields.This would provide new directions and strategies for the comprehensive treatment of complex diseases.

Multimodal fusion research in traditional Chinese medicine （TCM） inspection has greatly improved the accuracy of identification results with the help of emerging technologies in science and technology. At present， multimodal fusion technology is used in the integration of the parameters collected by the inspection instruments and the analysis of the parameters， which is represented by the development and application of the tongue inspection instrument， the face inspection instrument and the eye inspection instrument. However， the multimodal fusion research of TCM inspection has problems such as insufficient comprehensiveness and accuracy of parameter acquisition， difficulty in parameter integration for fusion analysis， and low clinical practicability of identification results. It is believed that， while keeping up with the cutting-edge science and technology， research on multimodal fusion of TCM inspection should be guided by the holism concept of TCM， and should focus on the enhancement of comprehensiveness and accuracy of multimodal parameter acquisition， standardisation of parameter fusion， and fusion of identification results， so as to gradually promote the objectivity， intelligence and modernisation of the four diagnostic methods of TCM.

ObjectiveTo retrospectively analyze the clinical efficacy of Xibining Ⅱ prescription in the treatment of knee osteoarthritis with cold-dampness blockage syndrome by oral medication and to explore the influencing factors of endpoint events. MethodA real-world retrospective cohort design was adopted， and medical records of knee osteoarthritis patients with cold-dampness blockage syndrome treated with oral medication from the orthopedics outpatient department of Jiangsu Province Hospital of Chinese Medicine were collected. All patients received conventional Western medicine treatment and were divided into non-exposure group （573 cases） and exposure group （427 cases） according to whether or not they received treatment with Xibining Ⅱ prescription. Descriptive analysis of the baseline data of the 1 000 screened cases was performed using IBM SPSS 27.0. According to the baseline data， 334 pairs were matched using the propensity score matching method， resulting in a total of 668 cases in both groups. The changes in visual analogous scale （VAS）， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） total score， Japanese Knee Osteoarthritis Measure （JKOM） score， and traditional Chinese medicine （TCM） syndrome score before treatment and at 2， 6， 12 weeks after treatment， as well as the incidence of adverse reactions， were compared between the two groups. A multivariate logistic regression analysis was conducted to analyze the influencing factors of endpoint events， with clinical cure judged based on the improvement rate of WOMAC total score before and after treatment. ResultAfter 12 weeks of treatment， compared to the results before treatment， the VAS， WOMAC total score， JKOM score， and TCM syndrome score of patients in both groups significantly decreased （P<0.01）. Compared to the non-exposure group， the exposure group showed a more significant reduction in VAS， WOMAC total score， JKOM score， and TCM syndrome score （P<0.01）. After 12 weeks of treatment， the clinical cure rate and significant efficiency were higher in the exposure group than in the non-exposure group （P<0.05）. Compared to the results before treatment within each group， VAS， WOMAC pain， stiffness， function scores， JKOM score， and TCM syndrome score significantly decreased at 2， 6， 12 weeks after treatment in both groups （P<0.01）. Compared to the non-exposure group at the same time points， the exposure group showed a reduction in VAS at 2， 12 weeks， WOMAC pain at 6， 12 weeks， and function scores at 12 weeks （P<0.05， P<0.01）. The JKOM score decreased at 6， 12 weeks， and the TCM syndrome score significantly decreased at 2， 6， 12 weeks in the exposure group （P<0.05， P<0.01）. Multivariate logistic regression analysis at 12 weeks showed that factors affecting clinical cure included the course of disease， history of alcohol consumption， hypertension， coronary heart disease， and the use of Xibining Ⅱ prescription （P<0.05， P<0.01）. Compared to the non-exposure group at the same time points， the incidence of epigastric discomfort in the exposure group was lower at 2， 12 weeks （P<0.01）， the incidence of diarrhea and vomiting was slightly higher than that in the non-exposure group， but the difference was not statistically significant. ConclusionThe clinical application of Xibining Ⅱ prescription combined with conventional Western medicine treatment in the treatment of knee osteoarthritis with cold-dampness blockage syndrome is more effective than conventional Western medicine treatment alone. It can significantly reduce VAS， WOMAC total score， JKOM score， and TCM syndrome score， with more pronounced long-term effects and a low incidence of adverse reactions.

Objective This study aims to analyze the proteomic characteristics of peripheral blood in patients with lung cancer coexistent with pulmonary tuberculosis(LC-PTB),identify the differential proteins compared with lung cancer(LC)patients,and conduct functional analysis on these proteins.Methods The study included 8 LC-PTB patients and 10 LC patients.The LC patients were newly diagnosed and confirmed by pathology and did not receive any anti-tumor treatment before,while the PTB patients were Mycobacterium tuberculosis positive at the time of sampling.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was applied to perform proteomic mass spectrometry to assess the differential proteins,and then functional analysis was conducted via bioinformatics.Results A total of 5,185 proteins were detected between two groups.Through differential expression screening,190 proteins(58 upregulated and 132 downregulated)were identified to be differentially expressed.Subcellular localization analysis revealed that the differential proteins were mainly concentrated in the cytoplasm,nucleus,and extracellular matrix.KEGG pathway and GO analysis showed the roles of differential proteins in biological processes including immune response,metabolism,and secretion regulation.Protein interaction network analysis highlighted the importance of SORT1,SAR1B,RPS6KB1,VWF,SHC1,SRPRB,CTSD,TARDBP,RPLP0,PSMA2,RPS6,XPO1,PRKACB,and HLA-DRB1 in LC-PTB.Additionally,the expression changes in proteins like ADA2,MAP3K1,and GLS2 might be closely associated with the development of LC-PTB.Conclusions The proteomic profile comprehensively described the proteomic characteristics of LC-PTB and identified numerous differentially expressed proteins,which could provide further clues for research on biological mechanism of LC-PTB.

OBJECTIVE To study the relationship between frequency specific free-field tone burst cortical auditory evoked potentials(CAEP)and aided behavioral audiometry to provide rapid,reliable insights for predicting hearing intervention efficiency in hard to cooperate cochlear implant patients.METHODS The study comprised of 22 cochlear implant pediatric patients(22 ears)free-field tone burst CAEP P1 response thresholds,free-field behavioral thresholds determined within the group across frequencies 0.5,1,2 and 4 kHz were collected for correlation analysis.RESULTS The free-field tone burst CAEP P1 response thresholds and free-field behavioral audiometric thresholds in cochlear implant pediatric patients for testing frequencies 0.5,1,2,4 kHz were compared and r correlation coefficients found were 0.567,0.670,0.637 and 0.762 across the frequencies respectively(P<0.01).The mean difference between free-field CAEP P1 response threshold and free-field behavioral thresholds for cochlear implant patients differ by 5-8 dB with statistical significance.CONCLUSION Free-field tone burst CAEP can be used for cochlear implant programming validation in patients that fail to cooperate in behavioral testing,thus is applicable in cochlear implant programming clinical practice.

AIM:This study investigates the effect of fibroblast growth factor 21(FGF21)long-acting ana-logue PF-05231023 on promoting the"browning"of white adipose tissue(WAT)by inhibiting mitophagy in WAT and the molecular mechanisms involved.METHODS:Using a high-fat diet(HFD)to replicate an obesity model in mice,18 C57BL/6J mice were divided into three groups:normal control(NC)group,HFD group,and PF-05231023 intervention(PF+HFD)group,each consisting of 6 mice.After 12 weeks of feeding,the mice were anaesthetized,their eyeballs were removed to collect blood samples,and serum was separated to measure levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)、alanine aminotransferase(ALT),and aspartate aminotransferase(AST)in mouse serum.The inguinal WAT(iWAT),epididymal WAT(eWAT)and liver were collected.Part of the tis-sues were used for Western blot experiments to measure the protein levels of"browning"related markers uncoupling pro-tein-1(Ucp-1)and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),as well as mitophagy-related markers PTEN-induced kinase 1(Pink1),parkin,beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ).Another part of the tissues was fixed in paraformaldehyde for subsequent HE and immunohistochemical staining.3T3-L1 cells were induced to mature adipocytes using the classic"cocktail"method.The CCK-8 assay was used to assess the impact of different concentrations of PF-05231023 intervention on cell viability.After 48 h of PF-05231023 intervention,the 3T3-L1 cell clumps were collected for Western blot experiments to measure the expression levels of"browning"related markers Ucp-1 and PGC-1α,as well as mitochondrial autophagy-related markers Pink1,parkin,beclin-1,and LC3-Ⅱ proteins.Oil red O staining was performed to detect cell accumulation,and immunofluorescence staining was used to mea-sure Ucp-1 protein content.Subsequently,3T3-L1 cells were divided into the normal group,PF-05231023 intervention group,Pink1 agonist MTK458 intervention group,and MTK458+PF-05231023 intervention group.Cell clumps were col-lected for Western blot experiments to measure the markers as mentioned above.RESULTS:The key findings of our study indicate that the PF-05231023 intervention did not affect energy intake in mice but significantly reduced the weight,liver weight,and fat weight of mice induced by a high-fat diet(P<0.05).The intervention also decreased lipid accumula-tion(TC,TG、LDL-C)and liver damage(ALT,AST)and alleviated hepatocyte vacuolization and adipocyte size(P<0.05).Compared with the HFD group,the PF-05231023 intervention increased the levels of Ucp-1 and PGC-1α protein expression in iWAT and eWAT(P<0.01).Immunohistochemical staining showed higher Ucp-1 protein content in the PF-05231023 intervention group than in the HFD group.The PF-05231023 intervention dose-dependently increased Ucp-1 and PGC-1α protein expression levels in mature 3T3-L1 cells(P<0.01),reduced cellular lipid accumulation,and immu-nofluorescence staining showed increased Ucp-1 protein content in mature 3T3-L1 cells after PF-05231023 intervention.The PF-05231023 intervention inhibited mitochondrial autophagy-related indicators Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels in iWAT,eWAT,and induced mature 3T3-L1 cells(P<0.05).The MTK intervention increased Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels,increased Ucp-1 protein expression level,compared with the MTK intervention group,after MTK and PF-05231023 co-intervention,partially decreased Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels,and partially restored Ucp-1 protein expression level(P<0.01).CONCLUSION:(1)Intervention with PF-05231023 can improve obesity and related metabolic disorders induced by a high-fat diet in mice;(2)PF-05231023 intervention can inhibit white adipose tissue(WAT)and induce mature 3T3-L1 cell mitochondria autophagy,promoting"browning"by inhibiting mitochondrial autophagy;(3)Its mechanism may be related to the inhibi-tion of the Pink1-parkin signalling pathway.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.