ObjectiveTo clarify the graded quantitative diagnostic characteristics of lung qi deficiency syndrome in chronic obstructive pulmonary disease （COPD） based on latent class analysis combined with a hidden structure model. MethodsClinical data， including the four diagnostic methods of traditional Chinese medicine （TCM）， were collected from 745 COPD patients with lung qi deficiency syndrome. Latent class modeling was performed using R 4.1.2 software， and each patient was classified into one of three severity categories （mild， moderate， or severe） based on probabilistic parameterization， parameter estimation， and model fitting. A database was established for different severity levels of lung qi deficiency syndrome. Based on this， Lantern 5.0 software was used to construct hidden structure models for mild， moderate， and severe lung qi deficiency syndrome， and syndrome differentiation rules were developed through comprehensive clustering. ResultsA latent class model was constructed using 28 symptoms and signs with a frequency greater than 10%. Considering TCM theory and model simplicity， the optimal model was determined when the number of latent classes was three， categorizing lung qi deficiency syndrome into mild （298 cases）， moderate （164 cases）， and severe （283 cases）. Hidden structure models were separately developed for each severity level， and syndrome differentiation rules were established. A comparison of common symptoms in the syndrome differentiation rules for mild and moderate lung qi deficiency syndrome showed no statistically significant differences in diagnostic values and weights （P＞0.05）， leading to their combined analysis and the development of a unified syndrome differentiation rule. Value and weight of quantitative diagnosis of mild-to-moderate lung qi deficiency syndrome were as followed： shortness of breath （diagnostic value 9.3， diagnostic weight 86.92%）， dyspnea on exertion （8.2， 76.64%）， low voice and reluctance to speak （6.7， 62.62%）， poor appetite （4.0， 37.38%）， loose stools （4.0， 37.38%）， weak cough sound （2.9， 27.10%）， wheezing （2.3， 21.50%）， fatigue （1.8， 16.82%）， spontaneous sweating （1.7， 15.89%）， susceptibility to colds （1.6， 14.95%）， swollen tongue （1.4， 13.08%）， teeth marks on the tongue edge （1.2， 11.21%）， deep pulse （1.6， 14.95%）， with a diagnostic threshold of 10.3. Value and weight of quantitative diagnosis of severe lung qi deficiency syndrome were as followed： weak cough sound （15.1， 61.13%）， soreness and weakness of the waist and knees （12.6， 51.01%）， shortness of breath （11.1， 44.94%）， low voice and reluctance to speak （8.3， 33.60%）， frequent nocturia （6.1， 24.70%）， spontaneous sweating （3.7， 14.98%）， susceptibility to colds （3.5， 14.17%）， teeth marks on the tongue edge （7.8， 31.58%）， pale tongue body （1.9， 7.69%）， white tongue coating （5.5， 22.27%）， thin pulse （1.5， 6.07%）， with a diagnostic threshold of 23.7. ConclusionThe combination of latent class analysis and a hideen structure model effectively clarified the graded quantitative diagnostic characteristics of lung qi deficiency syndrome， providing a reference for the quantitative diagnosis of other fundamental syndromes in TCM.

BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

Objective:To analyze the efficacy and influencing factors of cyclosporine(CsA)alone in the treatment of children with acquired aplastic anemia(AA).Methods:The clinical data of children diagnosed with AA and treated with CsA alone from January 1,2016 to December 31,2020 in the Children's Hospital of Chongqing Medical University were collected,and the efficacy and influencing factors of CsA treatment were evaluated.Results:Among the 119 patients,there were 62 male and 57 female,with a median age of 7 years and 1 month.There were 45 cases of very severe AA(VSAA),47 cases of severe AA(SAA),and 27 cases of non-severe AA(NSAA).At 6 months after treatment,the efficacy of VSAA was lower than that of SAA and NSAA,and there was a statistical difference(P＜0.01).6 cases died early,16 cases relapsed,2 cases progressed to AML and ALL.The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA,while high PLT count was a protective factor(P=0.008,P=0.002).The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5 × 109/L,68.5％,respectively.Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST(P=0.020,OR=0.062),and high PLT count was a protective factor(P=0.044,OR=1.038).At 3 months of treatment,CsA response and NSAA were the risk factor for recurrence(P=0.001,0.031).Conclusion:The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone.A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA,and a high proportion of bone marrow lymphocyte was an unfavorable factor.CsA response at 3 months and NSAA were risk factors for recurrence.

Autophagy often occurs after cells are attacked by oxidative stress, where damaged structures are phagocytic and degraded into nutrients, thereby reducing oxidative damage, promoting the survival of cancer cells and reducing the therapeutic effect of photodynamic therapy (PDT). However, excessive activation of autophagy can promote cell apoptosis. In this paper, the photosensitizer pyropheophorbide-a (Ppa) was used to produce a large amount of reactive oxygen species (ROS) to achieve the effect of killing cancer cells. At the same time, icaritin (Ica), an autophagy inducer, was used to over-activate autophagy, which transformed the protection of cancer cells into the promotion of cancer cell apoptosis, so as to improve the effect of photodynamic therapy. In this study, the interaction force between Ica and Ppa was exploited to successfully construct a self-assembled nanomedicine IP with good stability and high drug load. The synthesis method is simple, through using the drug itself as a carrier, and the loading capacity (LA) of Ica and Ppa can be increased to 83.53% and 16.45% without introducing potential biosafety risks of nanocarriers. Compared with free Ppa, self-assembled nanomedicine IP showed superior performance in cellular uptake and reactive oxygen species production. In addition, the self-assembled nanomedicine IP can reverse the protective autophagy induced by PDT by activating the autophagy of tumor cells, and facilitate apoptosis and antitumor coordination, which significantly improves the antitumor activity of PDT.

Objective:To explore the effect of fully automatic image segmentation of adenoid and nasopharyngeal airway by deep learning model based on U-Net network. Methods:From March 2021 to March 2022, 240 children underwent cone beam computed tomography（CBCT） in the Department of Otolaryngology, Head and Neck Surgery, General Hospital of Shenzhen University. 52 of them were selected for manual labeling of nasopharynx airway and adenoid, and then were trained and verified by the deep learning model. After applying the model to the remaining data, compare the differences between conventional two-dimensional indicators and deep learning three-dimensional indicators in 240 datasets. Results:For the 52 cases of modeling and training data sets, there was no significant difference between the prediction results of deep learning and the manual labeling results of doctors（P>0.05）. The model evaluation index of nasopharyngeal airway volume: Mean Intersection over Union（MIOU） s （86.32±0.54）%; Dice Similarity Coefficient（DSC）: （92.91±0.23）%; Accuracy: （95.92±0.25）%; Precision: （91.93±0.14）%; and the model evaluation index of Adenoid volume: MIOU: （86.28±0.61）%; DSC: （92.88±0.17）%; Accuracy: （95.90±0.29）%; Precision: （92.30±0.23）%. There was a positive correlation between the two-dimensional index A/N and the three-dimensional index AV/（AV+NAV） in 240 children of different age groups（P<0.05）, and the correlation coefficient of 9-13 years old was 0.74. Conclusion:The deep learning model based on U-Net network has a good effect on the automatic image segmentation of adenoid and nasopharynx airway, and has high application value. The model has a certain generalization ability.
Child ; Humans ; Adolescent ; Adenoids/diagnostic imaging* ; Image Processing, Computer-Assisted/methods* ; Pharynx ; Cone-Beam Computed Tomography ; Nose

Objective:To evaluate the clinical effects of adjustable traction skin stretchers used in repair of wounds at the lower leg, foot and ankle.Methods:A retrospective study was performed to analyze the clinical data of 56 patients who had been treated for skin defects at the lower leg, foot and ankle from August 2016 to September 2022 at The First Affiliated Hospital of Zhengzhou University, Honghui Hospital, Affiliated to Xi'an Jiaotong University Medical College, The First Affiliated Hospital of Henan Polytechnic University, and Yunnan Zhongde Orthopedic Hospital. There were 35 males and 21 females, aged (39.9±18.7) years. There were 43 traumatic wounds, 3 burns, 6 inflammatory wounds, 3 relief incisions due to osteofascial compartment syndrome, and 1 scar. The areas of skin defect ranged from 2.5 cm × 2.0 cm to 20.0 cm × 10.0 cm. The duration of wounds was (8.6±7.8) d. All the wounds were repaired with adjustable traction skin stretchers. The row-hook type of skin stretchers was used in 28 cases, the single-rod type in 20 cases, the single-rod type combined with an external fixator in 5 cases, and a combination of the row-hook type and the single-rod type in 3 cases.The time for wound traction closure, color of wound skin margin, skin swelling around the wound, functional recovery of affected limb and complications were recorded.Results:The time from skin stretching to wound closure was (7.8±3.8) d in the 56 patients. The color of wound skin edge after stretching was normal in 16 cases, dark red in 38 cases, and dark in 2 cases; the skin swelling around the wound was degree 1 in 21 cases, degree 2 in 33 cases, and degree 3 in 2 cases. The 56 patients were followed up for (8.9±4.1) months. Primary wound closure was achieved in 48 patients, and secondary wound closure in 8 patients after repair with an autologous skin graft. Partial skin necrosis occurred due to tension blisters after skin stretching in 2 patients, one of whom was repaired with an autologous skin graft and the other of whom by dressing change. Deep bone infection recurred in 2 patients whose wounds healed after their bone defects were repaired using Ilizarov technique of bone transfer. In the 56 patients, the muscle strength of the lower extremity beyond the wound was recovered to normal, and the range of motion of the joints adjacent to the wound also recovered to normal.Conclusion:In repair of wounds at the lower leg, foot and ankle, adjustable traction skin stretchers can lead to fine clinical effects and limited complications, because the stretchers can control the tension of skin digitally and precisely.

Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.
Male ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Monoclonal Gammopathy of Undetermined Significance ; Retrospective Studies ; Risk Factors ; Immunoglobulin Light Chains ; Disease Progression

AIM:To analyze the correlation between optical coherence tomography(OCT)parameters and central retinal vein occlusion of macular edema secondary(CRVO-ME), and compare the clinical efficacy of ranibizumab combined with laser photocoagulation and ranibizumab alone in the treatment of CRVO-ME.METHODS:There were 43 case with 43 eyes of patients in CRVO-ME diagnosed in our hospital from January 2020 to December 2020 included in the present study and divided into two groups, namely A and B. Patients in group A were treated with ranibizumab combined with laser photocoagulation, while patients in group B were treated with ranibizumab alone. The structure of outer retina and “SAVE” scores were observed and estimated using OCT and fluorescein angiography(FFA)examination before and after the treatment at 1, 3, 6, 12mo, and then analyzed their correlation with best corrected visual acuity(BCVA, LogMAR). The BCVA, central macular thickness(CMT), intraocular pressure and average number of drug injections were also compared between the two groups before and after treatment.RESULTS:At 12mo after treatment, the BCVA in the OCT baseline external limiting membrane(ELM)intact group and baseline ellipsoid zone(EZ)intact group before and after treatment were significantly improved than those of the fracture group(0.47±0.16 vs 0.21±0.15, P=0.013; 0.44±0.20 vs 0.25±0.17, P=0.008). There was no statistically significant difference in BCVA changes between baseline RPE fracture group and RPE intact group(P>0.05). The number of patients with “S” and “A” at 1 score decreased significantly at 12mo after treatment in both groups, the BCVA of patients with “V” and “E” at 0 score before treatment was significantly improved than those patients at 1 score(all P<0.05). The BCVA and CMT of patients after treatment in groups A and B were both significant improved compared with before treatment(P<0.05). There were no significant differences in the BCVA and CMT in the number of drug injections between the two groups(P>0.05). In addition, there were no severe complications such as secondary glaucoma and endophthalmitis in both groups.CONCLUSION: Baseline status of ELM and EZ, presence or absence of vitreoretinal abnormalities(V), and focal leakage(E)could suggest the treatment efficacy of CRVO-ME. Ranibizumab in the treatment of CRVO-ME demonstrates prominent efficacy and great safety, and there was no better effect was observed when combined with laser photocoagulation.

AIM: To evaluate the clinical efficacy of adalimumab(ADA)with dose-reduced glucocorticoid for the treatment of Vogt-Koyanagi-Harada disease(VKH).METHODS: A total of 21 patients(37 eyes)with VKH who received ADA therapy in the Department of Ophthalmology of our hospital from August 2020 to December 2021 were included. The interval of ADA administration was progressively extended after intraocular inflammation controlled and lasted for 3mo, and it returned to the initial treatment interval once the inflammation recurred. After follow-up for 12mo, anterior chamber cell(ACC)grade, vitreous haze(VH)grade, retinal/choroidal lesions, serous retinal detachment(SRD), best corrected visual acuity(BCVA), central macular thickness(CMT)and doses of glucocorticoid and immunosuppressant were compared before and after the first ADA injection. Treatment failure events and adverse reactions were recorded.RESULTS: Compared with baseline, the proportion of eyes with ACC grade ≤1+ and VH grade ≤1+ increased(P<0.05), the proportion of eyes with retinal/choroidal lesions decreased significantly(P<0.01), BCVA and CMT were significantly improved(P<0.01), and the average dose of glucocorticoid reduced significantly(P<0.01)at 2wk, 1, 3 and 6mo after treatment. At the final follow-up, 82% of patients received glucocorticoid ≤5 mg, and all patients stopped using immunosuppressant. There were 13 treatment failure events during the follow-up period, and 12 patients(57%)extended the ADA treatment interval, with no serious adverse events related to ADA treatment observed.CONCLUSION: ADA is effective and safe for the treatment of VKH, reducing the need for glucocorticoid and immunosuppressant. In addition, extending the interval of ADA treatment is effective, which has a lower recurrence rate.

Previously, we discovered that cells contain a 5-hydroxytryptamine (5-HT) degradation system (5DS), which includes 5-HT_2A receptor (5-HT_2AR), 5-HT synthase, and monoamine oxidase A (MAO-A). Among these, 5-HT_2AR has the ability to regulate the expression of 5-HT synthase and MAO-A, and activation of 5DS causes upregulation of these proteins at the same time, resulting in the production of reactive oxygen species (ROS) in the mitochondria. In this study, we investigated the relationship between interstitial pneumonia (IP) and 5DS activation, as well as the therapeutic effect of inhibiting 5DS on IP. Animal models of bleomycin (BLM)-induced IP in mice and radiation (Rad)-induced IP in rats were established, and the models were treated with the 5-HT_2AR antagonist sarpogrelate hydrochloride (SH), 5-HT synthesis inhibitor carbidopa (CDP), and their combination (SH∶CDP = 2∶1). The animal experiments were carried out in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. In the two IP models, immunohistochemistry staining and Western blot analysis showed that the expression of 5-HT synthase was significantly upregulated in all cells of lung tissue, while the expression of 5-HT_2AR and MAO-A was most significantly upregulated in the macrophages. Treatment with SH or CDP significantly reduced pulmonary interstitial thickening, alveolar atrophy with collapse, massive macrophage infiltration and interstitial fibrosis in the two IP models, as measured by HE and Masson staining, and a combination of both almost eliminated the lung tissue lesions. Moreover, treatment with the combination of SH and CDP almost completely eliminated increased ROS and malondialdehyde levels, decreased superoxide dismutase activity, increased tumor necrosis factor-α and interleukin-1β levels, and upregulated nuclear factor-κB phosphorylation and α‍-smooth muscle actin, matrix metalloproteinase-2, and collagen expression. SH and CDP worked together to create a synergistic effect. The findings suggested that the activation of 5DS, as evidenced by increased 5-HT synthesis in all cells of lung tissue and increased 5-HT synthesis and degradation in macrophages, is probably related to the occurrence of IP and that inhibition of 5DS can effectively treat IP.