AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

ObjectiveTo investigate the application value of a multimodal model integrating radiomics features， deep learning features， and clinical structured data in predicting severe acute pancreatitis （SAP）， and to provide more accurate tools for the early identification of SAP in clinical practice. MethodsThe patients with acute pancreatitis （AP） who attended The First Affiliated Hospital of Soochow University， Jintan Hospital Affiliated to Jiangsu University， and Suzhou Yongding Hospital from January 1， 2017 to December 31， 2023 were included. Related data were collected， including demographic information， previous medical history， etiology， laboratory test data， and systemic inflammatory response syndrome （SIRS） within 24 hours after admission， as well as imaging data within 72 hours after admission， while related scores were calculated， including Ranson score， modified CT severity index （MCTSI）， bedside index for severity in acute pancreatitis （BISAP）， and systemic inflammatory response syndrome， albumin， blood urea nitrogen and pleural effusion （SABP） score. The model was constructed in the following process： （1） three-dimensional CT images were used to extract and identify radiomics features， and a radiomics classification model was established based on the extreme gradient Boost （XGBoost） algorithm； （2） U-Net is used to perform semantic segmentation of three-dimensional CT images， and then the results of segmentation were imported into 3D ResNet50 to construct a deep learning classification model； （3） the predicted values of the above two models were integrated with clinical structured data to establish a multimodal model based on the XGBoost algorithm. The variable importance plot and local interpretability plot were used to perform visual interpretation of the model. The independent samples t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test or Fisher’s exact test was used for comparison of categorical data between groups. The receiver operating characteristic （ROC） curve was plotted for each model and existing scoring systems， and the area under the ROC curve （AUC） was calculated to assess their performance； the Delong test was used for comparison of AUC. ResultsA total of 609 patients who met the criteria were included， among whom 114 （18.7%） developed SAP. In this study， the data of 426 patients from The First Affiliated Hospital of Soochow University was used as the training set， and the data of 183 patients from Jintan Hospital Affiliated to Jiangsu University and Suzhou Yongding Hospital were used as the independent test set. The multimodal model had an AUC of 0.914 in the test set， which was significantly higher than the AUC of traditional scoring systems such as MCTSI （AUC=0.827）， Ranson score （AUC=0.675）， BISAP （AUC=0.791）， and SABP score （AUC=0.648）； in addition， the multimodal model showed a significant improvement in performance compared with the radiomics classification model （AUC=0.739） and the deep learning classification model （AUC=0.685） （the Delong test： Z=-3.23， -4.83， -3.48， -4.92， -4.31， and -4.59， all P <0.01）. The top 10 variables in terms of importance in the multimodal model were pleural effusion， predicted value of the deep learning model， predicted value of the radiomics model， triglycerides， calcium ions， SIRS， white blood cell count， age， platelets， and C-reactive protein， suggesting that the above variables had significant contributions to the performance of the model in predicting SAP. ConclusionBased on structured data， radiomic features， and deep learning features， this study constructs a multicenter prediction model for SAP based on the XGBoost algorithm， which has a better predictive performance than existing traditional scoring systems and unimodal models.

Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Objective:To describe the positive rates of high-risk human papillomavirus (HR-HPV) DNA and serum-neutralizing antibody in cervical intraepithelial neoplasia (CIN) tissues of rural women in Xiangyuan County, Shanxi Province, and evaluate the association of HR-HPV DNA and neutralizing antibody positive status with the occurrence of CIN.Methods:In a cohort of 1 897 women aged 35-45 years established by the Shanxi Province Cervical Cancer Screening StudyⅠ, DNA typing (SPF10 PCR-DEIA-LiPA25) was performed by using tissue samples of women with positive HR-HPV test results [Hybrid CaptureⅡ(HC2)] or abnormal cytological or pathological results. Serum HR-HPV neutralizing antibody detection was conducted with multicolor pseudovirion-based neutralization assay. Cochran-Armitage trend test was used to analyze the changing trend of the positive rate of HR-HPV DNA and neutralizing antibody with the progression of CIN. Multivariate logistic regression models were used to evaluate the influence and multiplicative interaction of HR-HPV DNA and neutralizing antibody positive status on the occurrence of CIN. The relative excess risk ( RERI), attributable proportion of interaction ( AP), and the synergy index ( SI) of the interaction were calculated to evaluate the additive interaction of HR-HPV DNA and neutralizing antibody on the occurrence of CIN. Results:The positive rate of any type of HR-HPV DNA (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) in 479 women who were HC2 positive or had abnormal cytological or pathological detection results was 37.16%. In normal, CIN1, CIN2, and CIN3+ groups, the HR-HPV DNA positive rates were 18.03%, 49.53%, 90.24% and 94.59%, respectively. The positive rate of any type of HR-HPV neutralizing antibody was 63.88%. In normal, CIN1, CIN2, and CIN3+ groups, the positive rates of HR-HPV neutralizing antibody were 63.95%, 57.94%, 70.73%, and 72.97%, respectively. The positive rate of any type of HR-HPV neutralizing antibody was 53.31% in 1 418 women who were HC2 negative and had normal cytopathology, and the most common types were HPV51 (27.36%) and HPV39 (24.96%). Multivariate logistic regression analysis showed that any type of HR-HPV DNA positive status ( OR=9.15, 95% CI: 5.99-14.20, P<0.001) was the independent factor for the occurrence of CIN, HR-HPV neutralizing antibody positive status was not associated with the occurrence of CIN ( OR=0.95, 95% CI: 0.61-1.48, P=0.815). The OR value of the multiplication of HR-HPV DNA and neutralizing antibody positive status of the occurrence of CIN was 1.63 (95% CI: 0.67-3.95), P=0.283. Quantitative analysis of interaction showed that RERI was 1.65 (95% CI:-3.56-6.86), SI was 1.28 (95% CI: 0.58-2.82), and AP was 0.19 (95% CI:-0.36-0.75). Conclusions:HR-HPV DNA positive status was a risk factor for the occurrence of CIN, but neutralizing antibody positive status was not associated with the occurrence of CIN. They had no significant multiplicative or additive interaction with the occurrence of CIN.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.