Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Objective:To analyse the clinical significance of selective single embryo transfer by time-lapse mo-nitoring(TLM)or conventional morphology assessment(CMA)in vitro fertilization/intracytoplasmic sperm in-jection and embryo transfer(IVF/ICSI-ET),and to initially explore the predictive value of Raman spectral analy-sis of embryo culture medium for clinical pregnancy rate.Methods:The study is a prospective randomized con-trolled clinical trial.We assigned 139 patients treated with IVF/ICSI-ET in Reproductive and Genetics Center of Suzhou Municipal Hospital from April 2019 to July 2020,which were randomly assigned to either the CMA or the TLM group.We performed selective single-embryo transfer(fresh cycle and FET)after selecting the optimal em-bryos with TLM or CMA respectively.If the patient's first embryo transfer was unsuccessful,a second one would be performed to compare the differences in the cumulative live birth rate of embryo transfer and other pregnancy outcomes between the two groups.Meanwhile,we collected 15 μl of embryo culture medium at day 3 after IVF/ISCI fertilization for Raman spectroscopy analysis.Results:There were no differences in cumulative live birth,cu-mulative clinical pregnancy,cumulative premature birth,cumulative early spontaneous abortion,cumulative ectopic pregnancy and LGA or SGA between TLM and CMA groups(P＞0.05).The Neonatal sex ratio in the TLM group was lower than that in the CMA group,but the difference was not significant(P＞0.05).Raman spectros-copy analysis of embryo culture medium predicted the clinical pregnancy rate with 67.21％accuracy.Conclu-sions:In young women with a good ovarian reserve,the advantage of using TLM to evaluate embryos is not obvi-ous,so we should remain vigilant that embryo selection based on morphokinetic parameters may affect the sex ratio.Raman spectroscopic analysis of embryo culture medium is not yet able to effectively predict the planting ability of embryos.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Objective:To compare the clinical characteristics and magnetic resonance imaging(MRI)features of isolated infarction of the splenium of the corpus callosum and reversible splenial lesion syndrome(RESLES).Methods:Clinical and imaging findings of 12 patients with a clinical diagnosis of isolated infarction of splenium of the corpus callosum and 13 patients with RESLES from Deportment of Neurology in Beijing Geriatric Hospital between December 2018 and November 2022 and follow-up results were retrospectively analyzed.Results:The patients with isolated infarction of SCC were older than the patients with RESLES(age of patients with isolated infarction of SCC: 67.6±9.2, age of patients with RESLES: 23.2±17.8).All patients with infarction had one to three risk factors for cerebrovascular diseases.Both two groups showed hyperintense lesions on T2WI, fluid-attenuated inversion recovery(FLAIR)and diffusion-weighted imaging(DWI), and hyperintense lesions on T1WI and a low apparent diffusion coefficient(ADC).Most SCC infarctions occurred unilaterally(one case with bilateral lesions and 12 cases with unilateral lesions), with irregular dot-like or patchy lesions.Nine patients in the infarction group completed the follow-up, during which the lesions did not disappear on the T1WI, T2WI, FLAIR and ADC sequence.One patient in this group had a recurrent stroke.In the RESLES group, all lesions were located on the midline of SCC, with round, oval or boomerang-shaped lesions.All patients in the RESLES group completed the follow-up, during which lesions either shrank or disappeared.Conclusions:Infarction and RESLES can both result in SCC lesions.The existence of risk factors and imaging features about the locations of lesions, the morphology, and lesion changes during follow-up are helpful in the differential diagnosis.

AIM To explore the effects and mechanism of Polygoni multiflori Radix Preparata(PMRP)ona rat model of post-stroke depression(PSD).METHODS The models of middle cerebral artery occlusion(MCAO)established by thread embolism method were then randomly divided into the model group,the positive drug(fluoxetine)group,and the low-dose and high-dose PMRP groups,with 10 rats in each group,in contrast to the 10 rats of the sham operation group.After 7 days of MCAO modeling,the rats underwent their 21-day PSD modeling except those of the sham operation group,during which the rats had their the neurological functions and behaviors assessed on the 1st,7th,14th and 21st day;and their cerebral infarction area and brain water content detected on the 21st day.HE staining,Nissl staining and immunohistochemical staining were used to observe the pathological morphology of cerebral ischemic penumbra.ELISA and Western blot were applied in the detections of the cerebral protein expressions of aquaporins(AQP3,AQP4,AQP5)and brain-derived neurotrophic factor(BDNF).RESULTS Compared with the model group,the high-dose PMRP group displayed improved neurological functions and behavioral scores(P＜0.05,P＜0.01),and reduced cerebral infarction area and brain water content(P＜0.05).Compared with the model group,each treatment group demonstrated clearer brain structure in ischemic penumbra,smaller intercellular space,increased neuron counts,decreased cerebral protein expressions of AQP3,AQP4 and AQP5(P＜0.05,P＜0.01),and increased BDNF protein expression(P＜0.05).CONCLUSION PMRP can reduce the depression of PSD rats by improving the microenvironment of neurons to promote their growth and survival,and eliminating the brain edema to enhance neurological functions via reduced protein expressions of AQP3,AQP4 and AQP5,and increased BDNF protein expression.

Objective To investigate the distribution patterns of traditional Chinese medicine(TCM)constitution in 959 patients with endometriosis(EMs).Methods From January 2019 to November 2019,959 EMs patients were selected from Guang'anmen Hospital of China Academy of Chinese Medical Sciences,Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical University,Beijing Hospital,Dongfang Hospital of Beijing University of Chinese Medicine,Beijing Friendship Hospital Affiliated to Capital Medical University,and Fuxing Hospital Affiliated to Capital Medical University.The general clinical information of the patients was recorded and then the TCM constitution was identified.After that,the correlation of TCM constitution distribution with concurrent constitution and the relationship of TCM constitution distribution with age and the complication of dysmenorrhea were analyzed.Results(1)The constitution types of EMs patients listed in descending order of the proportion were yang deficiency constitution(65.1％,624/959),qi stagnation constitution(58.4％,560/959),qi deficiency constitution(52.8％,506/959),blood stasis constitution(44.2％,424/959),phlegm-damp constitution(42.5％,408/959),damp-heat constitution(41.9％,402/959),yin deficiency constitution(39.6％,380/959),balanced constitution(26.8％,257/959),and inherited special constitution(16.6％,159/959).Among the patients,there were fewer patients with single constitution,accounting for 20.2％(194/959),and most of them had concurrent constitution types,accounting for 79.8％(765/959).(2)The association rule mining based on Apriori algorithm obtained 33 related rules.The concurrent constitution types of qi deficiency-yang deficiency,blood stasis-yang deficiency,and blood stasis-qi stagnation were the association rules with high confidence.(3)Compared with patients aged 35 years and below,the patients over 35 years old were predominated by high proportion of blood stasis constitution(P＜0.05).Compared with patients without dysmenorrhea,the patients with dysmenorrhea had the increased proportion of biased constitutions and the decreased proportion of balanced constitution(P＜0.05 or P＜0.01).Conclusion Yang deficiency constitution,qi stagnation constitution,qi deficiency constitution and blood stasis constitution are the high-risk constitution types of EMs patients.The concurrent constitution types are commonly seen in EMs patients,which are more common than single biased constitution.Management of EMs patients with the methods of warming yang,relieving stagnation,benefiting qi and activating blood will be helpful for correcting the biased constitutions in time and preventing disease progression,which will achieve the preventive treatment efficacy through TCM constitution correction.

Objective To observe the intervention effect and mechanism of Chinese herbal compound(Zhenyuan Granules)on overweight in mice caused by estrogen deficiency.Methods An ovariectomized female mouse model was established to observe the effects of intragastric 14 week administration of Zhenyuan Granules on body mass and fat accumulation in mice.The 3T3-L1 mouse preadipocyte model was constructed to observe the effect of Zhenyuan Granules intervention on adipogenic differentiation.The expressions of key genes/proteins regulating adipocyte formation and fat synthesis in mouse adipose tissue and 3T3-L1 cells was detected to explore the mechanism of lipid-lowering effect of Zhenyuan Granules in vivo and in vitro.Results Zhenyuan Granules significantly decreased the body mass gain(P＜0.01),perigonadal and inguinal fat indexes(P＜0.05),significantly inhibited the differentiation of 3T3-L1 preadipocytes into mature adipocytes(P＜0.01),significantly downregulated the expression levels of transcription factors peroxisome proliferators activated receptor γ(PPARγ)and sterol-regulatory element binding protein 1c(SREBP-1c)and enzymes acetyl-CoA carboxylase 1(ACC1)and fatty acid synthase(FAS)in adipose tissue and 3T3-L1 preadipocytes(P＜0.05),significantly enhanced the phosphorylation of AMP-activated protein kinase(AMPK)and ACC1(P＜0.05).Conclusion Zhenyuan Granules can inhibit the formation of adipocytes and improve the overweight of female mice caused by estrogen deficiency.The mechanism is related to the activation of AMPK signaling pathway.It is suggested that Bushen Jianpi Chinese herbal compound Zhenyuan Granules is helpful for body mass control in postmenopausal women.

Objective To investigate factors influencing the occurrence of early haematoma expansion(HE)in patients with spontaneous intracerebral hemorrhage(sICH),to develop a predictive model and evaluate its predictive efficacy.Methods A retrospective cohort of 238 patients with sICH,admitted to General Hospital of Western Theater Command between January 2017 and December 2022,was analyzed.Patients were categorized into two groups based on the criteria of HE exceeding 33%in relative volume or 6 ml in absolute volume:HE group(n=62)and non-haematoma expansion(NHE)group(n=176).Clinical characteristics,laboratory findings,Non-contrast Computed Tomography(NCCT)imaging,and Glasgow Coma Scale(GCS)scores were compared between the two groups.Multifactorial logistic regression analysis was employed to identify risk factors for HE and to model the probability of its occurrence.The R language rms package was utilized to construct a nomogram model for predicting HE in sICH patients,Additionally,the related clinical,NCCT,and GCS models were constructed.The predictive efficacy of each model for HE in sICH patients was evaluated using area under Receive Operative Characteristic(ROC)curve(AUC),and the clinical application value of each model was assessed using accuracy,sensitivity,specificity,and Jordon's index.The Delong test was applied to analyze differences in the predictive values of the models.Results Significant differences in satellite sign,vortex sign,and history of anticoagulant treatment were observed between two groups(P<0.05).Multifactorial logistic regression analysis revealed independent risk factors for HE in sICH patients,including the first CT examination time,homogeneity,history of anticoagulant medication,volume,maximal diameter,hypodensity sign,island sign,satellite sign,and vortex sign(P<0.05).The AUCs for the constructed clinical model,NCCT model,GCS model and nomogram model in predicting the occurrence of HE in sICH patients were 0.672,0.706,0.518 and 0.754,respectively.The nomogram model demonstrated higher accuracy,sensitivity,Jordon's index and AUC compared with those in the clinical and NCTT models.Conclusions The first CT examination time,homogeneity,history of anticoagulant treatment,volume,maximum diameter,hypodensity sign,island sign,satellite sign,and vortex sign are independent predictors of early HE in sICH patients.The nomogram model,constructed with the above parameters,demonstrated high predictive efficacy for HE and holds potential for clinical application.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

The current status of exoskeletons was introduced in enhancing individual soldier's battlefield rescue capabilities,promoting the integrated use of battlefield rescue equipment,protecting medical personnel on the battlefield and assisting injured soldiers in rehabilitation training.The challenges of exoskeletons faced in human-machine interaction,power supply endurance,heavy overall structure,restricted movement and high cost were analyzed when applied to medical service support,and some suggestions were proposed accordingly including enhancing technology research and development,integrated application,communication and cooperation and personnel training.References were provided for the application of exoskeletons in China's medical service support.[Chinese Medical Equipment Journal,2024,45(3):71-75]