Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Objective To investigate the effect and mechanism of dexmedetomidine(Dex)in alleviating sevoflurane(Sev)-induced cognitive dysfunction in neonatal rats via the Janus kinase 2/signal transducer and activators of transcription 3(JAK2/STAT3)signaling pathway.Methods A total of 50 neonatal Sprague-Dawley(SD)rats were randomly divided into control group,model group,Dex group,AG490 group,and Colivelin group,with 10 rats in each group.Except for control group,the rats in the other four groups were used to construct a model of cognitive dysfunction in neonatal rats by inhaling Sev.Before modeling,Dex group was intraperitoneally injected with 20 μg/kg Dex;AG490 group was intraperitoneally injected with 20 μg/kg Dex and 1 mg/kg AG490;Colivelin group was intraperitoneally injected with 20 μg/kg Dex,1 mg/kg AG490,and 1 mg/kg Colivelin;control group and model group were intraperitoneally injected with an equal doses of physiological saline.The novel object recognition test and step-down test were used to detect the cognitive,learning,and memory functions of neonatal rats.TUNEL method was used to detect the cell apoptosis rate in the hippocampus.Rhodamine 123 staining was used to detect the mitochondrial membrane potential in the hippocampus.ELISA method was used to detect the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in the hippocampus.DHE probe method was used to detect the intracellular reactive oxygen species(ROS)content.qRT-PCR was used to detect the mRNA expression levels of phosphorylated JAK2(p-JAK2),phosphorylated STAT3(p-STAT3),Synapsin-I,brain-derived neurotrophic factor(BDNF),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax).Western Blotting was used to detect the protein expression levels of p-JAK2,p-STAT3,JAK2,and STAT3 in the hippocampus.Results Compared with control group,model group showed cognitive and memory impairment,significantly increased apoptosis rate,increased levels of ROS and MDA,decreased SOD level,decreased mRNA expression levels of p-JAK2,p-STAT3,Synapsin-I,BDNF,and Bcl-2,increased Bax mRNA expression level,decreased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and decreased mitochondrial membrane potential in the hippocampus(P<0.05).Compared with model group,Dex,AG490,and Colivelin groups showed significantly improved cognitive and memory impairment,significantly decreased apoptosis rate,decreased levels of ROS and MDA,increased SOD level,increased mRNA expression levels of p-JAK2,p-STAT3,Synapsin-I,BDNF,and Bcl-2,decreased Bax mRNA level,increased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and increased mitochondrial membrane potential in the hippocampus(P<0.05).Compared with Dex group,AG490 and Colivelin groups exhibited cognitive and memory impairment,significantly increased apoptosis rate,increased levels of ROS and MDA,decreased SOD level,decreased mRNA expression levels of p-JAK2 and p-STAT3,Synapsin-I,BDNF,and Bcl-2,increased Bax mRNA expression level,decreased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and decreased mitochondrial membrane potential in the hippocampus(P<0.05).Compared with AG490 group,Colivelin group showed significantly improved cognitive and memory impairment,significantly decreased apoptosis rate,decreased levels of ROS and MDA,increased SOD level,decreased mRNA expression levels of p-JAK2 and p-STAT3,Synapsin-I,BDNF,and Bcl-2,increased Bax mRNA expression level,decreased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and increased mitochondrial membrane potential in the hippocampus,with statistically significant differences(P<0.05).Conclusion Dex can inhibit the oxidative stress in the hippocampus of brain tissue in Sev-induced neonatal rats and improve their cognitive,learning,and memory impairment,which may be related to the activation of JAK2/STAT3 signaling pathway.

Objective To carry out cervical cancer VMAT radiotherapy planning respectively with the single-criteria optimization(SCO)and multi-criteria optimization(MCO)modes of Raystation 4.7 planning system,and to provide references for selecting optimization mode clinically by comparing and analyzing the dosimetric parameters such as target dose distribution,exposure dose to organ at risk(OAR),monitor unit and beam-on time.Methods Ten cervical cancer patients who attended some hospital from February to December 2022 were retrospectively selected,and some VMAT plans were designed for them with the SCO mode of Raystation 4.7 planning system and then enrolled into a SCO group;other VMAT plans were redesigned with the MCO mode under the premise the setup conditions such as machine model and shot field angle were unchanged,and divided into a MCO group.The two groups were compared in terms of maximum dose(D2%),minimum dose(D98%),homogeneity index(HI)and conformity index(CI)of the planning target volume(PTV),beam-on time,monitor unit and exposure doses to OARs including bladder V50 Gy,V40 Gy and V30 Gy,rectum V50 Gy,V40 Gy and V30 Gy,small intestine V50 Gy,V40 Gy and V30 Gy and left and right femur V50 Gy,V40 Gy and V30 Gy.SPSS 22.0 software was used for statistical analysis.Results Both the two groups met clinical requirements.There were no significant differences between the two groups in D98%,CI,small intestine V50 Gy and left and right femur V40 Gy(P>0.05).The MCO group had the values of HI,D2%,V50 Gy,V40 Gy and V30 Gy,rectum V50 Gy,V40 Gy and V30 Gy,small intestine V40 Gy and V30 Gy and left and right femur V30 Gy lower than those of the SCO group,with the differences being statistically significant(P<0.05).The SCO group had less monitor units and shorter beam-on time when compared with the MCO group,with the differences being statistically siginificant(P<0.05).Conclusion When compared with the SCO mode-based VMAT plans,the MCO mode-based VMAT plans significantly decrease the exposure doses and volume to rectum,bladder and small intestine and raise the PTV homogeneity,while lower the treatment efficiency to some extent by increased monitor units and prolonged beam-on time.[Chinese Medical Equipment Journal,2025,46(9):39-44]

Purpose To investigate the incidence and risk of malignancy(ROM)of the Bethesda class Ⅰ/Ⅲ di-agnosis of thyroid nodules due to insufficient number of follicular cells,and to analyze the correlation between their in-sufficient cell volume and the characteristics of the nodules themselves from the perspective of ultrasound and histology.Methods Clinical data were collected from fine needle aspiration cytology(FNAC)of the thyroid gland.Review and statistical analysis was performed on cases with the Bethesda class Ⅰ/Ⅲ diagnosis due to insufficient cell volume.The incidence and the ROM of Bethesda class Ⅰ/Ⅲ diagnosis were calculated.BRAF V600E(+)or postoperative patho-logical indicating papillary thyroid carcinoma(PTC)was used as the criterion for malignancy.Then,we matched the Bethesda class Ⅱ/Ⅵ cases with sufficient cell volume as the control group.The ultrasound characteristics and histo-logical images of the two groups were compared and analyzed in order to reveal the correlation between the insufficient amount of penetrating cells and the objective characteristics of the nodule itself.Results There were 39 solid thyroid nodules with the Bethesda class Ⅰ diagnosis,with an incidence of 3.3％and a ROM of 38.5％,and 160 nodules with the Bethesda class Ⅲ diagnosis,with an incidence of 13.5％and a ROM of 59.4％.The incidence and ROM of nod-ules with C-TIRADS ≥4b(22.4％,67.6％)were higher than those of C-TIRADS ≤4a(12.7％,39.8％),and the differences were statistically significant(P＜0.001).Compared to the Bethesda class Ⅱ/Ⅵ nodules with sufficient cell volume,occurrence of the Bethesda class Ⅰ/Ⅲ nodules were significantly correlated with small nodules(maximal diameter＜5 mm),vertical growth(aspect ratio ≥ 1)and poor blood supply(no or little blood flow signals)(r=0.131,-0.230,0.237,P=0.008,＜0.001,＜0.001).They were also significantly correlated with the pathologic histologic structure of diffuse significant fibrosis of the interstitium and low parenchyma/interstitium composition ratio(about 1:1)(r=-0.269,-0.396,P=0.019,＜0.001).Conclusion Thyroid Bethesda class Ⅰ/Ⅲ nodules have a high ROM,and BRAF V600E detection is recommended as a tool of tiered management.Bethesda class Ⅰ/Ⅲ diagnosis of insufficient cell volume is more likely when the nodules are too small,grow vertically and lack blood sup-ply,presumably associated with extensive interstitial fibrosis and sparse parenchymal cells.

Objective To evaluate the efficacy and safety of transcatheter aortic valve implantation(TAVI)for the treatment of primary aortic valve regurgitation(NAVR)and to compare the difference in the choice of prosthetic valve size and the difference in complications with aortic stenosis(AS).Methods According to the definition of Valve Academic Research Consortium(VARC-3),143 patients with NAVR/AS treated with TAVI and patients with NAVR treated with surgical aortic valve replacement(SAVR)at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from March 2019 to September 2024 were selected,and clinical data on baseline,perioperative,and primary endpoint events were were retrospectively collected and compared.Results Forty-three patients with NAVR were treated with TAVI,with a device success rate of 86.0％and a surgical success rate of 95.3％.Subgroup comparisons:(1)NAVR-TAVI group than NAVR-SAVR group:patients in the TAVI group had a significantly shorter operative time than those in the SAVR group(P＜0.001);complete left bundle branch block was more likely to occur after TAVI(P=0.042),and complete right bundle branch block was more likely to occur after SAVR(P=0.044).SAVR postoperatively The incidence of congestive heart failure was higher(P=0.013),and the mortality rate was significantly higher in the SAVR group than in the TAVI group(P=0.019).(2)NAVR-TAVI group than AS-TAVI group:the differences in access selection,THV size[28(22,34)mm vs.24(22,32)mm,P=0.044]and proportion of THV overdiameter[14％(7％,20％)vs.7％(3％,11％),P＜0.001]were statistically significant.patients in AS and NAVR groups had 1 case of permanent pacing after TAVI treatment.In the AS and NAVR groups,there was 1 case of permanent pacemaker implantation after TAVI.2 patients in the AS group were converted to surgical treatment,and 6 patients died.Conclusions The use of"off-label"(transfemoral)and"on-label"(transapical)TAVI devices(both from domestic sources)is safer than SAVR for the treatment of NAVR,especially in elderly and high-risk patients.Compared with patients with AS treated with TAVI,larger diameter annulas are usually selected for NAVR,with higher rates of valve migration,but overall safety and efficacy are comparable to AS.

Objective To develop and validate a fast Monte Carlo(MC)-based patient-specific quality assurance(PSQA)tool using the treatment log files that is suitable to be used in the online adaptive radiotherapy for pencil beam scanning proton therapy(PBSPT-ART).Methods The proposed tool first used the delivery log file of a PBSPT plan to reversely reconstruct the PBSPT(rPBSPT)plan,and then used an in-house developed graphic processing unit(GPU)-accelerated virtual particle MC(VPMC)dose engine to calculate the dose distribution of the rPBSPT plan.The rPBSPT dose calculated by VPMC was then compared to the rPBSPT dose calculated by another independent MC dose engine(MCsquare),using 3D gamma analysis to verify the accuracy of VPMC calculation.As a demonstration of the feasibility of developed log file-based PSQA,the VPMC calculated dose of the rPBSPT plan was compared to the pre-delivery second check dose of the corresponding PBSPT plan calculated by MCsquare,using 3D gamma analysis.3D gamma analysis employes a criterion of 2 mm/2%/10%.Twenty patients with different disease sites were representatively selected to validate the efficiency and accuracy of the tool.Results The average calculation time of a rPBSPT plan by VPMC was(5.88±4.00)s in the accuracy verification.Compared to MCsquare,the passing rate of the 3D gamma analysis was 99.47%±0.72%.In the proposed PSQA tool demonstration,the passing rate of comparing the VPMC calculated rPBSPT dose to MCsquare calculated second check dose of the corresponding PBSPT plan was 98.91%±0.92%.Conclusion The accuracy and efficiency of the tool can meet the requirements of PSQA in the online PBSPT-ART workflow.

Objective To develop and validate a fast Monte Carlo(MC)-based patient-specific quality assurance(PSQA)tool using the treatment log files that is suitable to be used in the online adaptive radiotherapy for pencil beam scanning proton therapy(PBSPT-ART).Methods The proposed tool first used the delivery log file of a PBSPT plan to reversely reconstruct the PBSPT(rPBSPT)plan,and then used an in-house developed graphic processing unit(GPU)-accelerated virtual particle MC(VPMC)dose engine to calculate the dose distribution of the rPBSPT plan.The rPBSPT dose calculated by VPMC was then compared to the rPBSPT dose calculated by another independent MC dose engine(MCsquare),using 3D gamma analysis to verify the accuracy of VPMC calculation.As a demonstration of the feasibility of developed log file-based PSQA,the VPMC calculated dose of the rPBSPT plan was compared to the pre-delivery second check dose of the corresponding PBSPT plan calculated by MCsquare,using 3D gamma analysis.3D gamma analysis employes a criterion of 2 mm/2%/10%.Twenty patients with different disease sites were representatively selected to validate the efficiency and accuracy of the tool.Results The average calculation time of a rPBSPT plan by VPMC was(5.88±4.00)s in the accuracy verification.Compared to MCsquare,the passing rate of the 3D gamma analysis was 99.47%±0.72%.In the proposed PSQA tool demonstration,the passing rate of comparing the VPMC calculated rPBSPT dose to MCsquare calculated second check dose of the corresponding PBSPT plan was 98.91%±0.92%.Conclusion The accuracy and efficiency of the tool can meet the requirements of PSQA in the online PBSPT-ART workflow.

Objective To evaluate the efficacy and safety of transcatheter aortic valve implantation(TAVI)for the treatment of primary aortic valve regurgitation(NAVR)and to compare the difference in the choice of prosthetic valve size and the difference in complications with aortic stenosis(AS).Methods According to the definition of Valve Academic Research Consortium(VARC-3),143 patients with NAVR/AS treated with TAVI and patients with NAVR treated with surgical aortic valve replacement(SAVR)at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from March 2019 to September 2024 were selected,and clinical data on baseline,perioperative,and primary endpoint events were were retrospectively collected and compared.Results Forty-three patients with NAVR were treated with TAVI,with a device success rate of 86.0％and a surgical success rate of 95.3％.Subgroup comparisons:(1)NAVR-TAVI group than NAVR-SAVR group:patients in the TAVI group had a significantly shorter operative time than those in the SAVR group(P＜0.001);complete left bundle branch block was more likely to occur after TAVI(P=0.042),and complete right bundle branch block was more likely to occur after SAVR(P=0.044).SAVR postoperatively The incidence of congestive heart failure was higher(P=0.013),and the mortality rate was significantly higher in the SAVR group than in the TAVI group(P=0.019).(2)NAVR-TAVI group than AS-TAVI group:the differences in access selection,THV size[28(22,34)mm vs.24(22,32)mm,P=0.044]and proportion of THV overdiameter[14％(7％,20％)vs.7％(3％,11％),P＜0.001]were statistically significant.patients in AS and NAVR groups had 1 case of permanent pacing after TAVI treatment.In the AS and NAVR groups,there was 1 case of permanent pacemaker implantation after TAVI.2 patients in the AS group were converted to surgical treatment,and 6 patients died.Conclusions The use of"off-label"(transfemoral)and"on-label"(transapical)TAVI devices(both from domestic sources)is safer than SAVR for the treatment of NAVR,especially in elderly and high-risk patients.Compared with patients with AS treated with TAVI,larger diameter annulas are usually selected for NAVR,with higher rates of valve migration,but overall safety and efficacy are comparable to AS.