ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Objective: To explore the association between time to first cigarette (TTFC) and expiratory airflow limitation, so as to provide a reference for the prevention and control of pulmonary function decline. Methods: Based on the baseline survey of the China Multi-Ethnic Cohort (CMEC), the demographic, lifestyle behavior, smoking behavior, and TTFC data of permanent residents aged 30 to 79 years in Chengdu City were collected from 2018 to 2019. The TTFC was divided into ≤5, 6-30, 31-60, and >60 minutes. Expiratory airflow limitation was determined when the proportion of the measured peak expiratory flow to the predicted value was less than 80%. The association between TTFC and expiratory airflow limitation was analyzed using a multivariable logistic regression model, and subgroup analyses were conducted according to smoking cessation, age of starting smoking, smoking duration, average daily smoking volume, and the habit of deep inhalation into the lungs. Results: A total of 6 766 residents were investigated, among whom 6 402 were males, accounting for 94.62%. The median age was 52 (interquartile range, 19) years. A total of 2 468 residents were detected with expiratory airflow limitation, with a detection rate of 36.48%. Multivariable logistic regression analysis showed that after adjusting for demographics, lifestyle behavior, smoking cessation, age of starting smoking, smoking duration, average daily smoking volume, and the habit of deep inhalation into the lungs, TTFC ≤5 minutes (OR=1.203, 95%CI: 1.035-1.397) and 6-30 minutes (OR=1.174, 95%CI: 1.002-1.374) were associated with an increased risk of expiratory airflow limitation. Subgroup analyses showed that there was no interaction between smoking behavior and TTFC on the risk of expiratory airflow limitation (all P>0.05). Conclusion A shorter TTFC is associated with an increased risk of expiratory airflow limitation among residents aged 30 to 79 years, and the association is not affected by snoking behaviors such as smoking cessation, age of starting smoking, smoking duration and average daily smoking volume.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To verify the prognostic value of perineural invasion and lymphovascular tumor embolus for patients with gastric cancer undergoing gastrectomy and postoperative chemotherapy, and establish a prognostic prediction nomogram model.Methods:According to 7∶3 radio, 781 gastric cancer patients were randomly divided into training cohort and internal validation cohort. One hundred fifty patients were utilized as the external validation cohort. Univariate and multivariate analysis were performed to evaluate the prognostic value of perineural invasion and lymphovascular tumor embolus, and construct the dynamic nomogram. The concordance index (C-index), net reclassification index and integrated discrimination improvement index, receiver operating characteristic curve, calibration curves and decision curve analysis were used to evaluate the nomogram.Results:Perineural invasion ( HR=1.486, 95% CI: 1.150-1.919, P<0.01) and lymphovascular tumor embolus ( HR=1.321, 95% CI: 1.030-1.693, P<0.05) were independent prognostic risk factors for patients with gastric cancer after gastrectomy and postoperative chemotherapy. C-index (training cohort: 0.734, internal validation cohort: 0.755, external validation cohort: 0.715), net reclassification index (training cohort: 0.228 for 3-year and 0.213 for 5-year OS prediction; internal validation cohort: 0.211 for 3-year and 0.279 for 5-year OS prediction; external validation cohort: 0.220 for 3-year and 0.440 for 5-year OS prediction) and integrated discrimination improvement index (training cohort: 0.051 for 3-year and 0.041 for 5-year OS prediction; internal validation cohort: 0.027 for 3-year and 0.036 for 5-year OS prediction; external validation cohort: 0.063 for 3-year and 0.153 for 5-year OS prediction) indicated that the nomogram performed better than the traditional TNM staging system ( P<0.05). Conclusions:Perineural invasion and lymphovascular tumor embolus are independent prognostic risk factors of gastric cancer patients after postoperative chemotherapy. The novel dynamic nomogram model based on perineural invasion and lymphovascular tumor embolus provides better assistance in evaluating prognosis of gastric cancer patients.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To verify the prognostic value of perineural invasion and lymphovascular tumor embolus for patients with gastric cancer undergoing gastrectomy and postoperative chemotherapy, and establish a prognostic prediction nomogram model.Methods:According to 7∶3 radio, 781 gastric cancer patients were randomly divided into training cohort and internal validation cohort. One hundred fifty patients were utilized as the external validation cohort. Univariate and multivariate analysis were performed to evaluate the prognostic value of perineural invasion and lymphovascular tumor embolus, and construct the dynamic nomogram. The concordance index (C-index), net reclassification index and integrated discrimination improvement index, receiver operating characteristic curve, calibration curves and decision curve analysis were used to evaluate the nomogram.Results:Perineural invasion ( HR=1.486, 95% CI: 1.150-1.919, P<0.01) and lymphovascular tumor embolus ( HR=1.321, 95% CI: 1.030-1.693, P<0.05) were independent prognostic risk factors for patients with gastric cancer after gastrectomy and postoperative chemotherapy. C-index (training cohort: 0.734, internal validation cohort: 0.755, external validation cohort: 0.715), net reclassification index (training cohort: 0.228 for 3-year and 0.213 for 5-year OS prediction; internal validation cohort: 0.211 for 3-year and 0.279 for 5-year OS prediction; external validation cohort: 0.220 for 3-year and 0.440 for 5-year OS prediction) and integrated discrimination improvement index (training cohort: 0.051 for 3-year and 0.041 for 5-year OS prediction; internal validation cohort: 0.027 for 3-year and 0.036 for 5-year OS prediction; external validation cohort: 0.063 for 3-year and 0.153 for 5-year OS prediction) indicated that the nomogram performed better than the traditional TNM staging system ( P<0.05). Conclusions:Perineural invasion and lymphovascular tumor embolus are independent prognostic risk factors of gastric cancer patients after postoperative chemotherapy. The novel dynamic nomogram model based on perineural invasion and lymphovascular tumor embolus provides better assistance in evaluating prognosis of gastric cancer patients.

OBJECTIVE To study the chemical composition and the function of solid excipients in relieving the "nourishing and spleen-impairing" effect of Zhangbang nine steaming nine sun-dying Rehmanniae Radix(RR) by using UPLC-Q-TOF-MS technique. METHODS UPLC-Q-TOF-MS was used to collect the data of Zhangbang nine steaming nine sun-dying RR, and UNIFI platform and self-built database were used for the rapid qualitative analysis and identification of the chemical components of Zhangbang nine steaming nine sun-dying RR. The effect of solid excipients on the function of RR "nourishing and spleen-impairing" was investigated by establishing a mouse model of low gastric motility and measuring its gastric residual rate and small intestine propulsion rate. RESULTS The UPLC-Q-TOF-MS and UNFI platforms identified 76 chemical components in nine steaming nine sun-dying RR, including 9 iridoid glycosides, 11 phenylethyl glycosides, 31 flavonoids, 6 saccharides and 19 other compounds; the results of gastric emptying and small intestinal propulsion experiments on mice showed that Zhangbang nine steaming nine sun-dying RR had gastric emptying and intestinal propulsion effects. CONCLUSION This method can be used for the rapid identification and analysis of nine steaming nine sun-dying RR, which has solid excipients Citri Reticulatae Pericarpium and Amomi Fructus to alleviate the "nourishing and spleen-impairing" function of RR. This study can provide a reference for quality control and elucidation of the material basis of the medicinal effects of specialty beverage of Zhangbang nine steaming nine sun-dying RR.

Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

Objective:To investigate the feasibility of predicting the risk of spontaneous preterm birth in singleton pregnancy women with low risk of preterm birth by transabdominal-transvaginal ultrasound cervical length sequential screening in the second trimester.Methods:This prospective longitudinal cohort study included singleton pregnant women at 11-13 +6 gestational weeks who were admitted to Nanjing Drum Tower Hospital from January 2023 to September 2023. Transabdominal and transvaginal cervical lengths were measured during the mid-trimester fetal ultrasound scan at 18-24 weeks, and pregnancy outcomes were obtained after delivery. A short cervix was defined as a transvaginal cervical length of ≤25 mm, and the outcomes were defined as spontaneous preterm birth occurs between 20 and 36 +6 weeks and extremely preterm birth before 32 weeks. The area under the receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of predicting spontaneous preterm birth by transabdominal and transvaginal cervix length, as well as the effectiveness of predicting short cervix by transabdominal cervical length. The relationship between transabdominal and transvaginal cervical length was evaluated using a scatter plot. Results:A total of 562 cases were included in this study, comprising 33 cases of spontaneous preterm birth (7 cases occurring before 32 weeks) and 529 cases of term birth. (1) Compared to the term birth group, transabdominal cervical length (median: 37.6 vs 33.2 mm; Z=-3.838, P<0.001) and transvaginal cervical length (median: 34.0 vs 29.9 mm, Z=-3.030, P=0.002) in the spontaneous preterm birth group were significantly shorter. (2) The areas under the ROC curve for predicting spontaneous preterm birth by transabdominal and transvaginal cervical length were 0.699 (95% CI: 0.588-0.809) and 0.657 (95% CI: 0.540-0.774), respectively. The sensitivity, specificity and positive predictive value of transvaginal cervical length Conclusions:In singleton pregnancy women with low risk of preterm birth, transabdominal-transvaginal cervical length sequential screening can reduce unnecessary transvaginal ultrasounds by approximately 41% without missing the diagnosis of pregnant women with a short cervix. This method also enhances the effectiveness of transvaginal cervical length to spontaneous preterm birth.

Objective:To investigate the consistency of domestic F-STROKE, NeuBrainCARE MRI automatic post-processing software and RAPID MRI automatic post-processing software in the output of infarction core area volume, time-to-maximum volume and ischemic penumbra volume in patients with acute ischemic stroke.Methods:The research was cross-sectional. The clinical and imaging data of patients with acute ischemic stroke from January 2016 to March 2021 were retrospectively collected, including 149 cases from Shanghai Fourth People′s Hospital Affiliated to Tongji University (Center 1), 120 cases from Langfang Changzheng Hospital of Hebei Province (Center 2), and 45 cases from Wuzhou Workers Hospital (Center 3). All patients underwent diffusion weighted imaging (DWI) and dynamic magnetic sensitivity contrast-perfusion weighted imaging (DSC-PWI). RAPID, F-STROKE and NeuBrainCARE automatic post-processing software were used to perform automatic post-processing analysis of MRI images of all patients with acute ischemic stroke. The infarct core (apparent diffusion coefficient<620×10 -6 mm 2/s) volume, time-to-maximum (T max>6 s) volume and the ischemic penumbra (PWI-DWI mismatch) volume were output. The Wilcoxon test was used to analyze the difference between F-STROKE, NeuBrainCARE, and RAPID software outputs of infarct core volume, time to maximum peak volume, and ischemic penumbra volume. Bland-Altman and intraclass correlation coefficient ( ICC) were used to analyze the consistency of the infarct core volume, time-to-maximum volume and ischemic penumbra volume output by F-STROKE, NeuBrainCARE and RAPID software. Results:There were statistically significant differences in the core infarct volume between F-STROKE and RAPID software, NeuBrainCARE and RAPID software ( Z=-10.17, -5.43, both P<0.001). There were significant differences in the time-to-maximum volume between F-STROKE and RAPID software, NeuBrainCARE and RAPID software ( Z=-3.17, -5.51, both P<0.05). There was no significant difference in the ischemic penumbra volume between F-STROKE software and RAPID software ( Z=-1.43, P=0.153), and there was significant difference in the ischemic penumbra volume between NeuBrainCARE software and RAPID software ( Z=-6.45, P<0.05). Bland-Altman analysis showed that the values within the limits of agreement accounted for more than 93.31% of all point values. ICC analysis showed high agreement between F-STROKE, NeuBrainCARE, and RAPID software outputs of infarct core volume, time to maximum peak volume, and ischemic penumbra volume ( ICC>0.6). Conclusion:Domestic F-STROKE software, NeuBrainCARE software and RAPID software have good consistency in evaluating the infarct core volume, time-to-maximum volume and ischemic penumbra volume in patients with acute ischemic stroke, which is worthy of clinical promotion.