AIM:To analyze the clinical phenotypes and genotypes of children with incontinentia pigmenti(IP)and enhance clinicians' understanding of the condition.METHODS: A family with IP diagnosed in February 2020 at the ophthalmology department of People's Hospital of Ningxia Hui Autonomous Region was enrolled. The proband and family members underwent comprehensive systemic and ocular examinations. Peripheral venous blood was collected for DNA extraction, followed by whole-exome sequencing and MLPA assay to identify pathogenic variants. Corresponding treatments were administered based on the severity of fundus lesions, and ocular clinical features and therapeutic outcomes were monitored during follow-up.RESULTS: The child in this study was a female, aged 8 years, with typical skin changes and scarring alopecia and dental abnormalities at the time of initial consultation. The results of genetic testing suggested that the child carried a heterozygous deletion of exons 4-10 of the IKBKG gene chrX:153440010-153446570del. The child had asymmetric lesions in both eyes, with severe lesions in the left eye, atrophy of the eyeballs, and ocular B-ultrasound suggesting structural disturbances in the eye, and neovascularization was seen in the peripheral retina of the right eye, and the patient was given laser photocoagulation treatment for the right eye, and no progression of retinopathy was detected during follow-up.CONCLUSION:Children with IP have different ocular clinical phenotypes, and retinal vasculopathy is the main change. Early screening and timely and standardized treatment are crucial for children diagnosed with IP.

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

Objective To integrate tumor proliferation and immune-related biomarkers to construct a nomogram prediction model for predicting the prognosis of ovarian cancer patients.Methods We collected clinical information from patients diagnosed with epithelial ovarian cancer(EOC)between 2009 and 2013.Immunohistochemical staining was performed to detect the expression levels of KI67,epidermal growth factor receptor(EGFR)and programmed death-ligand 1(PD-Ll)in tumor tissues.We employed Lasso-Cox regression to identify variables and construct the nomogram model.We used time-dependent receiver operating characteristic(ROC)curves,concordance index,calibration curves,and decision curve analysis(DC A)curves to assess the model's discrimination,calibration,and net clinical benefit ability,respectively.Additionally,we conducted Kaplan-Meier survival analysis to assess the prognostic value of the model's risk score.Results We included a total of 131 EOC patients who were randomly assigned to the training set(n=79)and validation set(n=52)in a 6∶4 ratio.Lasso-Cox regression identified seven variables for constructing the nomogram prediction model.The AUCs for 1-,4-,and 6-year overall survival in the training set were 0.911,0.943,and 0.968,respectively,with a consistency index of 0.86[95％confidence interval(CI):0.81-0.91].In the validation set,the AUCs for 1-,4-,and 6-year overall survival were 0.830,0.797,and 0.828,respectively,with a consistency index of 0.71(95％CI:0.64-0.78).The calibration curves in both training and validation sets demonstrated strong agreement between model-predicted survival and actual outcomes(all P＞0.05).DCA curves indicated that the modeled net clinical benefit outperformed TNM staging.Patients with high-risk scores in the model exhibit poorer overall survival(P＜0.01)and progression-free survival(P＜0.01).Conclusion The successful development and validation of a nomogram prediction model based on tumor proliferation and immune-related biomarkers offer an efficient and straightforward clinical tool.This tool holds promise for enabling personalized treatment strategies for patients with ovarian cancer.

Objective To analyze the postmarketing safety characteristics of three immunomodulatory drugs(IMiDs)(thalidomide,lenalidomide and pomalidomide)in order to provide reference for clinical rational drug use.Methods The Open Vigil 2.0 tool was used to collect adverse drug event(ADE)reporting data from the U.S.Food and Drug Administration's(FDA)Adverse Event Reporting System(FAERS)between the first quarter of 2013 and the second quarter of 2022 for three IMiDs as primary suspect drugs.High frequency ADE was analyzed by mapping according to Medical Dictionary for Regulatory Activities(MedDRA terminology)25.0.The effective signals of adverse drug reactions(ADR)were screened according to the reporting odds ratio(ROR)and proportional reporting ratio(PRR)methods,and the high-intensity signals were analyzed.Results Among the top 20 ADEs,peripheral neuropathy,decreased blood count,thrombosis,skin squamous cell carcinoma and other ADEs occurred in all three drugs,but the distribution of the involved tissues and organs was different.Among the top 20 ADR signals,nearly half of the ADR signals of the 3 drugs were also in the high-frequency ADE range,among which 3 drugs showed increased human chorionic gonadotrophin,thalidomide and lenalidomide showed false positives in pregnancy tests,rectal adenocarcinoma and colorectal adenocarcinoma,and pomalidomide and lenalidomide showed decreased complete blood counts.Conclusion The overall ADE distribution of the three diamines is consistent,but there are some differences in the specific ADR signal characteristics.In clinical application,more attention should be paid to hemocytopenia,peripheral neuropathy,thrombus and second primary malignant tumors.

Objective To elucidate utilization patterns,cost and safety of Bruton's tyrosine kinase inhibitors(BTKi)in the real world.Methods A retrospective cohort was designed and constructed using real-world BTKi data from a single lymphoma center.Descriptive analysis was performed to describe the demographic and clinical characteristics of the population.Medicine utilization and cost were quantified by defined daily doses(DDDs)and defined daily dose cost(DDDc),respectively.A generalized estimating equation(GEE)was used to explore the potential influencing factors of platelet aggregation rate(PAR).Results The study cohort included 193 patients[median age,65 years;77(39.90％)women],most of whom received ibrutinib(n=109,56.48％),and 77.20％patients combined BTKi with chemotherapy or targeted therapy.The implementation of national negotiation policy had a large impact on medicine utilization and cost.The DDDs difference between the two BTKis was reduced from 18.55 to 1.41 times.The DDDc for ibrutinib decreased from 1 619.99 Yuan to 567.00 Yuan,and that for zanubrutinib from 706.25 Yuan to 340.00 Yuan was already lower than ibrutinib.Interruptions were more readily observed in patients treated with ibrutinib,and hematological toxicity was the main adverse drug event(ADE)leading to treatment interruption.Besides,the GEE model showed that combining BTKi with antiplatelet medication significantly decreases the PAR[β=-34.35％,95％confidence interval(CI):-41.60％--27.11％,P＜0.001].Compared to zanubrutinib,ibrutinib also notably reduces the PAR(β=-12.38％,95％CI:-24.50％--0.27％,P＜0.05).Conclusion After the implementation of national negotiation policy,there is no significant difference in the clinical preference for two BTKis.Compared with ibrutinib,zanubrutinib showed an advantage in terms of economic profile,treatment interruptions caused by ADE,and the effect on PAR.

As the country with the largest number of new cancer cases and deaths,China faces a serious situation with a large cancer population base,low relative survival rate,and low adherence to cancer screening.Neighboring Japan,which has the longest life expectancy in the world,has a much higher relative survival rate than China,despite having a similarly high cancer rate,due to its well-established system of cancer prevention and control.Being an Asian country,the major prevalent cancers in China and Japan are similar in spectrum and can be referred to more.This article introduces the construction of Japan's cancer life-cycle prevention and control system of"cancer prevention","cancer care",and"coexistence with cancer"starting from the three major goals of Japan's cancer prevention and control program,and focuses on the improvement of cancer screening in Japan and the improvement of cancer survival in China.It also highlights the means and methods used to increase the cancer screening rate in Japan,with a view to providing suggestions for cancer prevention and control in China.

ObjectiveTo evaluate the effectiveness of Gandou decoction （GDD） by analyzing theclinical efficacy of GDD combined with speech training on the treatment of dysarthria with endoretention of damp-heat in Wilson's disease （WD）， so as to provide more clinical data and theoretical support for the selection of appropriate treatment schemes for WD patients with dysarthria with endoretention of damp-heat. MethodA total of 60 eligible WD patients with dysarthria with endoretention of damp-heat were selected and divided into a control group and a treatment group according to the random grouping method， with 30 cases in each group. The control group was treated with speech training + sodium dimercaptopropanesulfonate （DMPS）， and the treatment group was combined with GDD on the basis of the control group， with eight days as a course of treatment for 32 days. The total clinical effectiveness rate （Goldstein clinical classification）， dysarthria grading assessment from China Rehabilitation Research Center， TCM syndrome scores， 24-hour urine copper content， and modified Frenchay dysarthria rating scale scores of the two groups were compared before and after treatment. ResultAfter treatment， the total effective rate of the observation group was 90.0% （27/30）， and that of the control group was 70.0% （21/30）. The total effective rate of the observation group was significantly higher than that of the control group （Z=-1.986，P<0.05）. After treatment， the modified Frenchay dysarthria score， dysarthria grading assessment from China Rehabilitation Research Center， and 24-h urine copper in the two groups were significantly increased （P<0.05， P<0.01）， and the TCM syndrome score was significantly decreased （P<0.01）. Compared with the control group after treatment， except for the respiratory and jaw score， the modified Frenchay dysarthria score of the observation group was significantly increased （P<0.05， P<0.01）. The dysarthria grading from China Rehabilitation Research Center and 24-h urine copper content were significantly increased （P<0.01）， and the observation group had better efficacy. During the study period， there were no serious adverse reactions such as fever， rash， oral and eyelid mucosal swelling， exfoliative dermatitis， vomiting， diarrhea， or allergic shock during copper excretion treatment of DPMS and oral administration of GDD. ConclusionGDD combined with speech training can improve the symptoms and efficacy of WD patients with dysarthria with endoretention of damp-heat and enhance the patients' living standard to a certain extent， which can be widely used in clinics.

Rapid epidemiological screening for tuberculosis (TB) usually uses tuberculin pure protein derivative (PPD) skin test, which has limitations such as low specificity and high side effects. ESAT-6 and CFP-10 are secreted proteins of Mycobacterium tuberculosis, but the related genes are missing from Bacillus Calmette-Guerin (BCG). In this study, the fusion protein ESAT6-CFP10 (EC) was expressed and purified, and prepared into chitosan nanoparticles (EC-NPs), which were loaded into the microneedle patch and carried out the preliminary test of tuberculosis skin test. The drug loading capacity of MNP-EC-NPs (microneedle patch, MNP) can reach 0.03 μg per needle and 1.92 μg per patch. The shelf life of MNP-EC-NPs can reach 6 months at room temperature, and it can effectively penetrate the epidermis. Volunteer skin test results showed that MNP-EC-NPs can effectively distinguish between BCG vaccinators, and can effectively show positive reaction in the skin of tuberculosis patients without significant side effects. The experiment was approved by the Ethics Committee of Wuhan Pulmonary Hospital [2022 (2)]. In this study, a TB skin test method was established, using ESAT6-CFP10 fusion protein instead of PPD, and using soluble microneedle dosage form, which improved the specificity of TB skin test diagnosis and provided a new technical scheme for TB epidemic screening.

Jinqi Jiangtang Capsule (JQJTC) is clinically used for the prevention and treatment of type 2 diabetes, but the contents of its main chemical components are not yet clear. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for the determination of 15 components in JQJTC, including new chlorogenic acid, chlorogenic acid, cryptochlorogenic acid, formononetin, ononin, calycosin, calycosin-7-glucoside, astragaloside IV, berberine, epiberberine, berberrubine, coptisine, jatrorrhizine, palmatine and magnoflorine. The method was used to determine the contents of 15 components in the capsule and then to investigate the influence of excipients on the contents of the components in JQJTC. The separation was performed on a ACQUITY UPLC BEH C₁₈ column (100 mm × 2.1 mm, 1.7 μm) with a mobile phase consisting of 0.1% acetic acid and 5 mmol·L^-1 ammonium acetate (A) and acetonitrile (B) with gradient elution at a flow rate of 0.3 mL·min^-1 and a column temperature at 40 ℃. Electron spray ionization was used for mass spectrometry in positive ion mode. The established method meets the requirements of methodology of content determination in Chinese pharmacopoeia. The contents of 15 components in JQJTC varied from high to low. The top 5 contents were berberine, chlorogenic acid, magnoflorine, coptisine, and cryptochlorogenic acid, accounting for 87.31% of the total content. The contents of 10 components, including the alkaloids of coptidis rhizoma (berberine, epiberberine, berberrubine, coptisine, jatrorrhizine, palmatine and magnoflorine) and the organic acids of honeysuckle (new chlorogenic acid, chlorogenic acid, and cryptochlorogenic acid) in the whole formula extract without excipients was significantly lower than that in the capsule. These components accounted for 99.20% of the determined component contents. In this experiment, an accurate, sensitive and efficient UHPLC-MS/MS method for the determination of multi-components in JQJTC was established, which stably and reliably detected the contents of 15 components in the capsule and could provide the basis for more comprehensive quality analysis. It was also found that excipients had an increasing effect on the contents of detected alkaloid and organic acid components, which may be beneficial to the effectiveness of the capsules.

OBJECTIVE To introduce the clinical value assessment model for innovative drugs in Canada’s health insurance access， providing a reference for improving the clinical value assessment system for innovative drugs in China. METHODS The clinical value assessment system for innovative drugs in Canada’s health insurance access was organized from four aspects： the assessment body， the assessment process， the assessment dimensions， and the application of assessment results. A deep analysis was also conducted with the clinical value assessment of health insurance access for blinatumomab as an example. Then the suggestions were proposed for the improvement of relevant work in China. RESULTS & CONCLUSIONS Canada has established an independent clinical value assessment agency， the Canadian Agency for Drug and Technologies in Health （CADTH）， which is responsible for the health technology assessment of innovative drugs. The health insurance access to clinical value assessment system for innovative drugs is built with patient needs as the guide， and the review process includes stages such as opinion review and expert assessment. Different evaluation dimensions are set for oncology and non-oncology drugs， and the assessment is based on sufficient evidence and a transparent process. The assessment results include four types： reimbursement， conditional reimbursement， time-limited reimbursement， and non-reimbursement， balancing efficacy and accessibility. It is suggested that China should strengthen the clinical value assessment system for innovative drugs in health insurance access from four aspects： establishing a specialized institution for the clinical value assessment of innovative drugs， increasing the clarity of policy expectations， including patient benefit assessment indicators， and adding special reimbursement pathways for drugs.