Objective To explore the symptom prevalence in the patients with pulmonary nodules in Lingnan area and to investigate the influencing factors,thus to provide data support for the construction of differentiation and treatment system of symptoms-syndrome elements-syndromes-constitutions for patients with pulmonary nodules,and to promote the establishment of secondary prevention system of lung cancer with the in-depth participation of traditional Chinese medicine(TCM).Methods A cross-sectional study was adopted to investigate patients with pulmonary nodules who admitted in the First Affiliated Hospital of Guangzhou University of Chinese Medicine from August 2023 to January 2024.Data collection covered the basic information,clinical characteristics and symptoms of the patients.Likert four-level scale was used for the grading of the severity of the symptoms,multivariate linear regression was adopted to construct three regression models,and then the factors influencing the severity of symptoms of patients with pulmonary nodules were explored.Results(1)A total of 274 patients were enrolled in the analysis,including 160 females and 114 males,with a mean age of(54.44±12.00)years old and the symptom scores averaging(3.97±3.80)point.The included patients with pulmonary nodules were characterized by females outnumbering males,a higher proportion of middle-aged and elderly people,multiple pulmonary nodules being more common.(2)The analysis of the symptoms of the 274 patients showed that symptoms with an incidence over 30%were fatigue(116 cases,42.34%),cough(105 cases,38.32%),expectoration of white sputum(89 cases,32.48%),and irritability and distress(87 cases,31.75%).(3)Multivariate linear regression analysis after variable adjustment suggested that the overall symptomatic severity in the male was milder than that in the female[β=-1.67,95%CI(-2.67,-0.68),P<0.001],and symptom score was positively correlated with age[β=0.07,95%CI(0.03,0.10),P<0.001],history of exposure to secondhand smoke[β=1.27,95%CI(0.26,2.27),P=0.015],history of exposure to other hazardous substances[β=1.96,95%CI(0.39,3.53),P=0.015],and history of allergy[β=2.38,95%CI(1.22,3.54),P<0.001]significantly.Conclusion The overall symptoms of patients with pulmonary nodules in Lingnan area are mild,and the high prevalence of symptoms are fatigue,cough,expectoration of white sputum,and irritability and distress.The symptom severity is correlated with gender,age,history of exposure to secondhand smoke,history of exposure to other hazardous substances,and history of allergy.

OBJECTIVE: To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS). METHODS: A adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X). RESULTS: Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c.206+2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the proband's mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION The heterozygous splice site variant c.206+2T>G of the SMAD3 gene probably underlay the disease in this patient. Above discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.
Adult ; Humans ; Male ; Exome Sequencing ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Pedigree ; Smad3 Protein/genetics*

Objective:To observe the effects of transcranial direct current stimulation (tDCS) on functional connectivity (FC) in language-related brain regions of patients with picture-naming dysfunction after cerebral infarction by using resting state functional magnetic resonance imaging(rs-fMRI).Methods:Twenty-eight patients with post-infarction picture-naming dysfunction were divided into an acute stage group( n=16) and a recovery stage group( n=12) according to the course of the disease, and 18 middle-aged and elderly volunteers were recruited as the normal control group.The anodic tDCS was applied on the posterior perisylvian region(PPR) of the left sylvian of the patients, 5 days a week for 2 weeks.Before and after the 2 weeks′ treatment, the rs-fMRI and Psycholinguistic Assessment of Chinese Aphasia (PACA)-picture-naming subscale were performed, and FC changes in language-related brain areas were observed. Results:After treatment, the PACA scores of patients in both acute and recovery stage groups were significantly improved after treatment( P<0.05). Compared with normal subjects, FC in multiple brain regions and particularly the Wernicke area was reduced in both cerebral hemispheres among the patient group. It was more severe in the dominant hemisphere.After the tDCS treatment, FC in both frontotemporal lobes and in the Wernicke area was significantly enhanced in both the acute and recovery groups. Further comparison showed that in the acute group FC in both temporo-occipital lobes was significantly enhanced after treatment. In the recovery group, the enhanced FC in the left temporal lobe before the treatment was significantly reduced after treatment. Conclusion:The fMRI technique can evaluate changes in brain connectivity in aphasia patients with picture-naming dysfunction after cerebral infarction accurately and non-invasively.tDCS may improve picture-naming function of stroke patients by enhancing the FC in bilateral language-related brain areas(concentrated in frontotemporal lobes) and Wernicke area.

ObjectiveTo investigate the tumor inhibition effect and mechanism of Yifei Sanjie Pills （益肺散结丸， YSP） on lung cancer. MethodsLewis lung cancer tumor-derived mice were established and divided into four groups including model control group， cisplatin group， cisplatin + YSP low-dose group and cisplatin + YSP high-dose group， with 12 mice in each group. The corresponding interventions were given for 14 days. The tumor volume was measured on the 0th， 3rd， 7th， 10th and 14th days of administration to evaluate the tumor growth. The plasma and tumor tissue were collected on the 15th day. Plasma from the model group， the cisplatin group and the cisplatin+YSP high-dose group were selected， and plasma exosomes were extracted； the differences in miRNA expression among the groups were detected and analyzed by second-generation sequencing technology， and the potential mechanism of action of YSP was investigated by principal component analysis， biofunctional enrichment analysis and miRNA-target gene regulatory network analysis. Quantitative real-time PCR was used to detect the expression of miRNA-615-3p in tumor tissues， and the relationship between miRNA-615-3p and overall survival of lung cancer were analyzed using the Kaplan-Meier plotter （kmplot.com） database. ResultsCompared to that of the model control group， the tumor volume of the cisplatin group on day 10， and the cisplatin + YSP low- and high-dose groups on day 7， 10， and 14 were significantly reduced （P＜0.05 or P＜0.01）. Compared to that of the cisplatin group， the tumor volume of the cisplatin + YSP low- and high-dose groups on day 10 and 14 was significantly reduced （P＜0.05）. The principal component analysis of miRNA expression profiles showed significant differences in miRNA expression between different intervention groups. There were 21 differentially expressed miRNAs between the model control group and the cisplatin group， 50 differentially expressed miRNAs between the model control group and the cisplatin+ YSP high-dose group， and 6 differentially expressed miRNAs between the cisplatin group and the cisplatin+ YSP high-dose group. Biological function enrichment analysis showed that the differentially expressed miRNAs were mainly involved in the regulation of signaling pathways related to cell growth， proliferation， differentiation， autophagy and other biological activities. The miRNA-target gene regulatory network showed the top 20 genes that were targeted， among which there were proven miRNAs and genes related to lung cancer， and miRNAs that needed further investigation. The expression of miRNA-615-3p in tumor tissues decreased significantly in the cisplatin group and cisplatin+YSP high-dose group compared to that of the model group（P＜0.05 or P＜0.01）. The miRNA-615-3p was negatively correlated with the survival prognosis of lung cancer（P＜0.05）. ConclusionCisplatin combined with YSP can effectively inhibit the proliferation of Lewis lung cancer tumors， and the tumor-suppressive effect is related to the regulation of multiple miRNAs， especially the downregulation of miRNA-615-3p expression.

Objective:To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin′s lymphoma (R/R cHL).Methods:Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded.Results:In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment.Conclusion:Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin′s lymphoma in children.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective:To document any effect of transcranial direct current stimulation (tDCS) on the picture naming ability of stroke survivors with aphasia.Methods:Twenty-eight aphasic stoke survivors with picture naming dysfunction were divided into an acute group (with a course of disease of <1 month) and a convalescent group (with a course of disease of 2 to 6 months). Eighteen healthy subjects well-matched for age, gender and years of education formed the healthy control group. The patient group received tDCS once a day, 5 days a week for 2 weeks. Before and after the intervention, they were assessed using the Chinese psycholinguistic aphasia assessment (PACA) instrument. The activation of speech-related brain areas in everyone was quantified using resting state functional magnetic imaging (rs-fMRI).Results:After treatment the average PACA image naming scores of both the acute and convalescent groups had improved significantly. ALFF showed significant positive activation in the patient group′s right inferior temporal gyrus and negative activation in their left posterior central gyrus, while ReHo was significantly and positively activated in the right orbital superior frontal gyrus, the left medial superior frontal gyrus, the pericalar fissure cortex and the left parietal gyrus. It was, however, significantly negatively activated in the right posterior central gyrus. In the acute stage group, the ALFF was significantly and positively activated in the right superior frontal gyrus and right angular gyrus after the treatment, while the significant positive ReHo activation was in the right direct gyrus, the right angular gyrus, the right superior frontal gyrus and the right inferior temporal gyrus. In the convalescent group after the intervention the ALFF was significantly and positively activated in the left middle occipital gyrus and the right fusiform gyrus but negatively and significantly activated in the right insula, while ReHo was significantly and positively activated in the left superior temporal gyrus and the right angular gyrus.Conclusions:tDCS can improve the image naming of aphasic stroke survivors. The compensatory activation of language function is mainly in the right hemisphere in the acute stage, but in the convalescent stage the unimpaired brain area of the left cerebral hemisphere is also activated. The long-term recovery of language functioning may be the result of synergy between the hemispheres.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Objective To provide new ideas for promoting wound healing by digging and sorting out the medication rules in ancient classics and modern literatures. Methods The prescriptions for promoting wound healing recorded in literatures were collected to establish the database. The data mining technology was used for the analysis. Results 75 prescriptions and 203 traditional Chinese medicines were recorded in the ancient TCM literatures for promoting wound healing. The core medicines included frankincense, liquorice, angelica sinensis, angelica dahuricae, cortex phellodendri, myrrh, etc. They mainly belong to the class of clearing-heat drugs, promoting-circulation drugs, reinforcing drugs, relieving drugs, detoxification and tissue granulation drugs. Cluster analysis and association rule analysis were conducted for 16 core drugs. 4 cluster combinations ,15 groups of drug pairs and drug group association rules were obtained. Conclusion The prescription rules for wound healing mainly included clearing heat, promoting circulation, reinforcing, relieving, detoxification, and promoting tissue granulation. TCM wound treatment should be based on syndrome differentiation for fever, blood stasis, deficiency, anabrosis, exterior syndrome and poisoning.