Research progress on signal pathways related to prevention and treatment of hypertension target organ damage by traditional Chinese medicine / 中国药房

Hypertension is a common cardiovascular disease. At present， the prevalence and mortality of hypertension in China continue to rise， the morbidity and mortality of complications remain high. The continuous increase of blood pressure can cause damage to multiple target organs such as heart， brain， kidney and blood vessels. This article reviews the research progress of signal pathways related to the prevention and treatment of hypertension target organ damage by traditional Chinese medicine， and summarizes six signal pathways related to RhoA/ROCK， renin-angiotensin-aldosterone system， endothelin-1/nitric oxide， transforming growth factor-β1/Smads， phosphatidylinositide 3-kinases/protein kinase B， and Toll-like receptor 4/nuclear transcription factor-κB， in order to provide theoretical evidence for further research on clinical diagnosis and treatment of hypertension and its target organ damage.

Clinical Characteristics and Diagnostic Methods of Pulmonary Mucormycosis / 中山大学学报(医学科学版)

ObjectiveTo summarize the clinical features and prognosis of pulmonary mucormycosis （PM） in southern China， and to explore the diagnostic value of metagenomic next generation sequencing （mNGS） in PM. MethodsThe clinical manifestations， diagnosis， treatment and prognosis of patients diagnosed with PM in The First Affiliated Hospital of Sun Yat-sen University from January 1， 2019 to January 31， 2022 who had undergone mNGS detection in lung tissue or alveolar lavage fluid were collected retrospectively. A total of 14 patients with PM were included， including 4 patients with confirmed diagnosis and 10 patients with clinical diagnosis. ResultsAll patients had underlying medical conditions， with hematological malignancies and diabetes being the most common. The most common symptoms were fever （n = 10）， cough （n = 9） and shortness of breath （n = 9）. Consolidation was the most common sign of chest CT， followed by mass， mostly with cavity. On laboratory tests， decreased CD4+T lymphocytes， elevated CD8+T lymphocytes， and decreased CD4+/CD8+ ratio， and presentation with pleural effusion indicate poor prognosis. The positive rate of mNGS diagnosis was 78.5%， which was significantly higher than that of histopathology （50%）， fungus rapid fluorescence staining （61.5%） and fungal culture （23.1%） of bronchoalveolar lavage fluid. ConclusionsPulmonary mucormycosis is more likely to occur in patients with underlying diseases or who are immunocompromised. The clinical manifestations lack specificity. The low CD4/CD8 ratio and presentation of pleural effusion on CT imaging indicate poor prognosis of patients. mNGS is a rapid， convenient and sensitive method for the diagnosis of PM， which has advantages in the diagnosis of pulmonary mucormycosis.

Establishment and application value of a radiomics prediction model for lymph node metas-tasis of gallbladder carcinoma based on dual-phase enhanced CT / 中华消化外科杂志

Objective:To investigate the establishment and application value of a radio-mics prediction model for lymph node metastasis of gallbladder carcinoma based on dual-phase enhanced computed tomography (CT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 194 patients with gallbladder carcinoma who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2012 to December 2020 were collected. There were 70 males and 124 females, aged (64±10)years. All patients underwent curative-intent resection of gallbladder carcinoma. A total of 194 patients were randomly divided into 156 cases in training set and 38 cases in test set according to the ratio of 8:2 based on random number method in R software. The training set was used to establish a diagnostic model, and the test set was used to validate the diagnostic model. After the patients undergoing CT examination, image analysis was performed, radiomics features were extracted, and a radiomics model was established. Based on clinicopathological data, a nomogram prediction model was established. Observation indicators: (1) lymph node dissection and histopathological examination results; (2) establishment and characteristic analysis of a radiomics prediction model; (3) analysis of influencing factors for lymph node metastasis of gallbladder carcinoma; (4) establishment of a nomogram prediction model for lymph node metastasis; (5) comparison of the predictive ability between the radiomics prediction model and nomogram prediction model for lymph node metastasis. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers, and comparison between groups was performed by the chi-square test. Univariate analysis was conducted by the chi-square test, and multivariate analysis was performed by the Logistic regression model forward method. The receiver operating characteristic curve was drawn, and the area under curve, decision curve, confusion matrix were used to evaluate the predictive ability of prediction models. Results:(1) Lymph node dissection and histopathological examination results. Of the 194 patients, 182 cases underwent lymph node dissection, with the number of lymph node dissected as 8(range, 1?34) per person and the number of positive lymph node as 0(range, 0?11) per person. Postoperative histopathological examination results of 194 patients: 122 patients were in stage N0, with the number of lymph node dissected as 7(range, 0?27) per person, 48 patients were in stage N1, with the number of lymph node dissected as 8(range, 2?34) per person and the number of positive lymph node as 1(range, 1?3) per person, 24 patients were in stage N2, with the number of lymph node dissected as 11(range, 2?20) per person and the number of positive lymph node as 5(range, 4?11) per person. (2) Establishment and characteristic analysis of a radiomics prediction model. There were 107 radiomics features extracted from 194 patients, including 18 first-order features, 14 shape features and 75 texture features. According to the intra-group correlation coefficient and absolute median difference of each radiomics feature, mutual information, Select K-Best, least absolute shrinkage and selection operator regression were conducted to further reduce dimensionality. By further combining 5 different machine learning algorithms including random forest, gradient boosting secession tree, support vector machine (SVM), K-Nearest Neighbors and Logistic regression, the result showed that the Select K-Best_SVM model had the best predictive performance after analysis, with the area under receiver operating characteristic curve as 0.76 in the test set. (3) Analysis of influencing factors for lymph node metastasis of gallbladder carcinoma. Results of univariate analysis showed that systemic inflammation response index, carcinoembryonic antigen (CEA), CA19-9, CA125, radiological T staging and radiological lymph node status were related factors for lymph node metastasis of patients with gallbladder cancer ( χ2=4.20, 11.39, 5.68, 11.79, 10.83, 18.58, P<0.05). Results of multivariate analysis showed that carcinoembryonic antigen, CA125, radiological T staging (stage T3 versus stage T1?2, stage T4 versus stage T1?2), radiological lymph node status were independent influencing factors for lymph node metastasis of patients with gallbladder carcinoma [ hazard ratio=2.79, 4.41, 5.62, 5.84, 3.99, 95% confidence interval ( CI) as 1.20?6.47, 1.81?10.74, 1.50?21.01, 1.02?33.31, 1.87?8.55, P<0.05]. (4) Establishment of a nomogram prediction model for lymph node metastasis. A nomogram prediction model was established based on the 4 independent influencing factors for lymph node metastasis of gallbladder carcinoma, including CEA, CA125, radiological T staging and radiological lymph node status. The concordance index of the nomogram model was 0.77 (95% CI as 0.75?0.79) in the training set and 0.73 (95% CI as 0.68?0.72) in the test set, respectively. (5) Comparison of the predictive ability between the radiomics predic-tion model and nomogram prediction model for lymph node metastasis. The receiver operating characteristic curve showed that the areas under the curve of Select K-Best_SVM radiomics model were 0.75 (95% CI as 0.74?0.76) in the training set and 0.76 (95% CI as 0.75?0.78) in the test set, respectively. The areas under the curve of nomogram prediction model were 0.77 (95% CI as 0.76?0.78) in the training set and 0.70 (95% CI as 0.68?0.72) in the test set, respectively. The decision curve analysis showed that Select K-Best_SVM radiomics model and nomogram prediction model had a similar ability to predict lymph node metastasis. The confusion matrix showed that Select K-Best_SVM radiomics model had the sensitivity as 64.29% and 75.00%, the specificity as 73.00% and 59.09% in the training set and test set, respectively. The nomogram had the sensitivity as 51.79% and 50.00%, the specificity as 80.00% and 72.27% in the training set and test set, respectively. Conclusion:A dual-phase enhanced CT imaging radiomics prediction model for lymph node metastasis of gallbladder carcinoma is successfully established, and its predictive ability is good and consistent with that of nomogram.

Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis / 医学前沿

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34+ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34+ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.

KIF17 Modulates Epileptic Seizures and Membrane Expression of the NMDA Receptor Subunit NR2B / 神经科学通报·英文版

Epilepsy is a common and severe brain disease affecting >65 million people worldwide. Recent studies have shown that kinesin superfamily motor protein 17 (KIF17) is expressed in neurons and is involved in regulating the dendrite-targeted transport of N-methyl-D-aspartate receptor subtype 2B (NR2B). However, the effect of KIF17 on epileptic seizures remains to be explored. We found that KIF17 was mainly expressed in neurons and that its expression was increased in epileptic brain tissue. In the kainic acid (KA)-induced epilepsy mouse model, KIF17 overexpression increased the severity of epileptic activity, whereas KIF17 knockdown had the opposite effect. In electrophysiological tests, KIF17 regulated excitatory synaptic transmission, potentially due to KIF17-mediated NR2B membrane expression. In addition, this report provides the first demonstration that KIF17 is modified by SUMOylation (SUMO, small ubiquitin-like modifier), which plays a vital role in the stabilization and maintenance of KIF17 in epilepsy.

Cloning and function analysis of chalcone isomerase gene and chalcone synthase gene in Lonicera macranthoides / 中国中药杂志

In order to explore the functions of genes of key rate-limiting enzymes chalcone isomerase(CHI) and chalcone synthase(CHS) in the biosynthesis of flavonoids in Lonicera macranthoides, this study screened and cloned the cDNA sequences of CHI and CHS genes from the transcriptome data of conventional variety and 'Xianglei' of L. macranthoides. Online bioinformatics analysis software was used to analyze the characteristics of the encoded proteins, and quantitative reverse-transcription polymerase chain reaction(qRT-PCR) to detect the expression of CHI and CHS in different parts of the varieties at different flowering stages. The content of luteo-loside was determined by high performance liquid chromatography(HPLC) and the correlation with the expression of the two genes was analyzed. The results showed that the CHI and CHS of the two varieties contained a 627 bp and 1170 bp open reading frame(ORF), respectively, and the CHI protein and CHS protein were stable, hydrophilic, and non-secretory. qRT-PCR results demonstrated that CHI and CHS of the two varieties were differentially expressed in stems and leaves at different flowering stages, particularly the key stages. Based on HPLC data, luteoloside content was in negative correlation with the relative expression of the genes. Thus, CHI and CHS might regulate the accumulation of flavonoids in L. macranthoides, and the specific functions should be further studied. This study cloned CHI and CHS in L. macranthoides and analyzed their expression for the first time, which laid a basis for investigating the molecular mechanism of the differences in flavonoids such as luteoloside in L. macranthoides and variety breeding.

Drug-coated balloon for in-stent restenosis in femoropopliteal segment: 1-year clinical outcomes from a multicenter study in China / 中华普通外科杂志

Objective:To evaluate the safety and efficacy at 1-year follow-up of the use of drug-coated balloon (DCB) for the treatment of femoropopliteal in-stent restenosis (ISR).Methods:This study enrolled 252 patients undergoing Orchid DCB angioplasty for peripheral arterial disease in the femoral-popliteal segment. The clinical data were retrospectively analyzed.Results:Forty-nine patients were eligible, including 29 (59.2%) chronic total occlusions belonging to TransAtlantic Inter-Society Consensus-Ⅱ(TASC Ⅱ) D, 7 (14.3%) thrombosis, and 14 (28.6%) moderate to severe calcifications. The mean lesion length was (215.9±97.1) mm. 69.4% were of occlusive lesions (Tosaka Ⅲ category). Only 1 provisional stent was implanted. 98% patients had severe claudication or even worse. Of these cases, 34 (73.9%) showed improvements in Rutherford category, while 11 (23.9%) did not change and 1 (2.2%) case deteriorated. The average value of ABI was 0.478±0.264 before surgery and 0.907±0.207 at the end of follow-up. The improvement in Rutherford category ( P<0.01) and ABI ( P<0.005) were both significant. The primary patency (PP) was 80.4%, and the freedom from clinically driven TLR was 84.8% at 1 year. During the follow-up period, there was no all-cause death and major limb amputation. Conclusion:This multicenter study demonstrated the effectiveness of DCB as a treatment for complicated and extensive ISR lesions within 12 months.

Influence of function movement on the outcome of ankylosing spondylitis under the treat-to-target stratery / 中华风湿病学杂志

Objective:To investigate the effect of baseline function movement assessment of ankylosing spondylitis (AS) on treatment outcomes.Methods:The clinical data of 90 patients with AS who met the medical insurance treatment for major disease in Chengdu were collected including clinical symptoms, functional movement screen (FMS) and ankylosing spondylitis disease activity score (ASDAS) after 24 weeks adalimumab treatment. They were divided into the non-treat-to-target group and the non-treat-to target group based on the ASDAS score, t-test or χ2 test was used to compare the differences between the two groups. Logistic regression model was used to analyze the influence of baseline FMS on the outcome of patients reaching the treatment target. Results:① The two groups were different in the FMS [(15.8±2.3) vs (12. 6±2.5), t=6.17, P<0.001], squat [(2.2±0.6) vs (1.7±0.5), t=3.57, P=0.001], hurdle spanning [(2.2±0.7) vs (1.8±0.6), t=2.11, P=0.038], straight lunge [(2.3±0.7) vs (1.7±0.5), t=4.23, P<0.001], shoulder flexibility [(2.5±0.6) vs (2.2±0.8), t=2.21, P=0.037], active straight leg raise [(2.1±0.6) vs (1.8±0.6), t=2.35, P=0.021], spinal stabilization pushups [(2.4±0.7) vs (1.8±0.8), t=3.76, P<0.001], body rotation stability [(2.2±0.7) vs (1.6±0.8), t=3.42, P=0.001] at baseline. ② The two groups were different in ASDAS score [(0.96±0.28) vs (2.19±0.52), t=14.69, P=0.000], FMS [(17.4±1.9) vs (12.7±2.8), t=9.77, P<0.001], deep squat [(2.6±0.5) vs (1.5±0.5), t=9.09, P<0.001], hurdle step [(2.2±0.6) vs (1.8±0.8), t=2.80, P=0.006], straight lunge [(2.6±0.6) vs (1.8±0.9), t=4.85, P<0.001], shoulder flexibility [(2.8±0.4) vs (2.5±0.5), t=2.10, P=0.038], active straight leg raise [(2.2±0.6) vs (1.9±0.8), t=2.46, P=0.016], spinal stability push-ups [(2.8±0.4) vs (1.6±0.7), t=10.36, P<0.001], and body rotation stability [(2.3±0.7) vs (1.6±0.8), t=4.76, P<0.001] at the end of the observation. ③ The cut-off value of the FMS for predicting whether AS patients meet the standard at baseline was 14.25 points (Sensitivity 0.733, specificity 0.800). ④ Logistic regression results showed that in the baseline, FMS series of action tests, squat [ OR (95% CI)=0.155 (0.035, 0.677), P=0.013], straight lunge [ OR (95% CI)=0.375 (0.148, 0.953), P=0.039], spinal stability push-ups [ OR(95% CI)=0.136(0.043, 0.436), P=0.001], and body rotation stability [ OR(95% CI)=0.308 (0.121, 0.780), P=0.013] were the influencing factors of the AS patient's treatment outcome ( P<0.05). Conclusion:The AS patients in the non-treat-to-target group have better FMS tests at baseline and at the end of the study than the non-treat-to-target group. Squats, straight lunges, remember stable push-ups, and body rotation stability are the influencing factors for the treatment outcomes of AS patients at baseline.

Application of molecular imaging in chimeric antigen receptor T cell therapy / 中华核医学与分子影像杂志

Chimeric antigen receptor T cell (CAR-T) therapy, a novel immunotherapy, shows great potential in the treatment of hematological tumors to conventional therapies. Great progress has been made over the past few decades in the treatment of relapsed/refractory acute/chronic lymphocytic leukemia. However, due to the lack of real-time monitoring methods, it is impossible to predict and assess the therapeutic effect during the treatment of blood tumors, and we cannot learn more about the complications and risks. Many challenges exist in the clinical transformation of CAR-T therapy. As a non-invasive method, molecular imaging shows promise on real-time visualization of the biological behavior of CAR-T in vivo. Tracking CAR-T by directly labeling or indirectly evaluation by reporter gene methods has achieved breakthroughs. This article reviews the current situation of monitoring systems of CAR-T therapy and future expectations for each of the methods presented.

Preparation of N- 18F-fluoroethyl-tofacitinib and its application in the imaging of rheumatoid arthritis / 中华核医学与分子影像杂志

Objective:To synthesize N- 18F-fluoroethyl-tofacitinib, and explore its feasibility in the diagnosis of rheumatoid arthritis (RA). Methods:The " two-step method" was used to modify tofacitinib with 18F-fluoroethyl, and the labeling rate and radiochemical purity of the probe were measured by high performance liquid chromatography (HPLC), and the stabilities of the probe in vivo and in vitro were investigated. BALB/c mice (normal group; n=3) and collagen-induced arthritis (CIA) model mice (CIA group; n=3) were injected with N- 18F-fluoroethyl-tofacitinib and CIA model mice injected with tofacitirrib and N- 18F-fluoroethyl-tofacitinib were as blocking group ( n=3). All mice underwent microPET imaging and the percentage injection dose per gram of tissue (%ID/g) and the uptake ratio of inflamed joints to muscle (T/M) were calculated. One-way analysis of variance and the least significant difference (LSD) t test were used to analyze the data. Results:The synthesis time of N- 18F-fluoroethyl-tofacitinib was about 120 min, with the yield approximately 1%, the specific activity >13.6 GBq/μmol, and the radiochemical purity >99%. After the probe incubated with PBS, plasma or in vivo for 2 h, the radiochemical purity was still more than 95%. MicroPET imaging showed that 30 min after injection, the uptake of N- 18F-fluoroethyl-tofacitinib in the inflamed joints of CIA group was higher than that of normal group and blocking group ((10.22±1.64), (2.71±0.26) and (2.81±0.33) %ID/g; F=58.26, t values: 7.83, 7.67, P values: 0.001, 0.002). The T/M of CIA group was also higher than that of normal group and blocking group (24.73±5.77, 2.75±1.36 and 2.89±0.54; F=40.64, t values: 6.42, 6.53, P values: 0.003, 0.003). Conclusions:N- 18F-fluoroethyl-tofacitinib is successfully prepared and it is stable in vitro with good imaging performance in vivo. It may be used in clinic for the diagnosis of RA.

Study on the effect of functional movement on the recurrence of patients with ankylosing spondylitis after treat-to-target therapy / 中华风湿病学杂志

Objective:To investigate the effect of functional movement assessment on the recurrence of patients with ankylosing spondylitis (AS) after treat-to-target therapy.Methods:The clinical data of 61 patients with AS in Chengdu were collected including clinical symptoms and AS disease activity (ASDAS). After 24 weeks adalimumab treatment, motor function score of AS patients(ASDAS<1.3) was assessed by functional movement screen (FMS), then adalimumab was discontinued and the rest of the concurrent drugs were continued until the disease relapse or up to 1 year. The data of the two groups were compared using t-test analysis and Cox proportionate hazard model. Results:① The recurrence rate of patients with AS after treat-to-target therapy within 1 year follow-up was 57.4%; ② The recurrence group was younger [(27±7) vs (31±6), t=5.96, P=0.02], the ASADAS value was at the high end when adalimumab was withdrawal [(1.29±0.07) vs (0.87±0.16), t=177.31, P<0.01], and the FMS value was lower after treat-to-target [(12.9±2.7) vs (16.2±1.9), t=29.23, P<0.01], The time to reaching the treatment target was longer [(2.9±1.2) month vs (1.7±0.6) month, t=19.89, P<0.01] than the stable group; ③ The cut-off value of the FMS test of AS patients after treat-to-target therapy was 14.25 (sensitivity was 84.6%, specificity was 80%) . The time to treat-to-target was a risk factor for recurrence ( RR=2.285, P<0.05), and the FMS value after treat-to-target was a protective factor ( RR=0.625, P<0.05). Conclusion:After discontinuing the adalimumab, about half of the patients relapse. The time reaching the treatment target and the FMS value after treat-to-target therapy are the risk factors for disease recurrence.

Prevalence and associated factors for malnutrition among human immunodeficiency virus-exposed uninfected children from 2013 to 2019 in Hunan Province / 中华传染病杂志

Objective:To analyze the prevalence of malnutrition among human immunodeficiency virus-exposed uninfected (HEU) children and to identify the associated factors in Hunan Province.Methods:All children born to human immunodeficiency virus (HIV)-infected mothers retrieved from Information System of Prevention of Mother-to-Child Transmission of human immunodeficiency virus Management (IPMTCT) in Hunan Province between July 2013 and June 2019 were included. Information including maternal demographic characteristic, maternal comorbidities/complications, anti-retroviral therapy during pregnancy, anti-retroviral prophylaxis for children, birth weight, and disease during follow-up was collected. The length and weight of children at one, three, six, nine, 12 and 18 months of follow-up time points were detected, and the prevalences of stunting, underweight, wasting and malnutrition among HEU children were evaluated. The generalized estimating equation was used to fit the logistic regression model to analyze the associated factors for malnutrition.Results:A total of 656 HEU children were finally included. The prevalences of stunting, underweight, wasting, and malnutrition among HEU children were highest at one month of age, which were 11.9%(78/656), 9.1%(60/656), 7.0%(45/656) and 21.0%(138/656), respectively. Maternal comorbidities/complications (adjusted odds ratio (a OR)=2.30, 95% confidence interval ( CI) 1.48 to 3.58), mono/dual anti-retroviral therapy during pregnancy (a OR=2.38, 95% CI 1.54 to 3.68), birth weight <2 500 g (a OR=2.66, 95% CI 1.69 to 4.21) and disease during follow-up (a OR=1.73, 95% CI 1.10 to 2.70) were the risk factors for malnutrition among HEU children (all P<0.050). Both taking zidovudine (a OR=0.60, 95% CI 0.38 to 0.94) and nevirapine (a OR=0.31, 95% CI 0.18 to 0.52) for anti-retroviral prophylaxis were the protective factors for malnutrition among HEU children (both P<0.050). Conclusions:The prevalence of malnutrition among HEU children is high. The prevalence of malnutrition is affected by maternal comorbidities/complications, anti-retroviral therapy during pregnancy, and birth weight, diseases during follow-up and anti-retroviral prophylaxis for children.

A case of very early onset inflammatory bowel disease / 中国综合临床

The clinical data of a child with very early onset inflammatory bowel disease (VEO-IBD) treated in the digestive department of Guangzhou Women's and children's Medical Center in October 2018 were analyzed retrospectively. The patient was hospitalized because of "shortness of breath and abdominal distension" after birth. The gastrointestinal manifestations were diarrhea, mucus bloody stool, feeding intolerance and weight loss; the extraintestinal manifestations were liver function damage and joint damage. Endoscopic examination considered VEO-IBD. The patients were treated with infliximab and enteral nutrition. When the clinical symptoms were relieved and the gastrointestinal mucosa healed, the enteral nutrition regimen was adjusted. At present, she returned to daily diet, and the weight and height reached the level of normal children. VEO-IBD patients can be combined with a variety of extraintestinal manifestations, clinicians need to identify the coexistence of these diseases, effective follow-up.

Predictive value of clinical radiomics model based on nnU-Net for prognosis of gallbladder carcinoma / 中华消化外科杂志

Objective:To investigate the predictive value of clinical radiomics model based on nnU-Net for the prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 168 patients who underwent curative-intent radical resection of GBC in the First Affiliated Hospital of Xi'an Jiaotong University from January 2012 to December 2020 were collected. There were 61 males and 107 females, aged (64±11)years. All the 168 patients who underwent preoperative enhanced computed tomography (CT) examina-tion were randomly divided into 126 cases in training set and 42 cases in test set according to the ratio of 3:1 based on random number table. For the portal venous phase images, 2 radiologists manually delineated the region of interest (ROI), and constructed a nnU-net model to automatically segment the images. The 5-fold cross-validation and Dice similarity coefficient were used to evaluate the generalization ability and predictive performance of the nnU-net model. The Python software (version 3.7.10) and Pyradiomics toolkit (version 3.0.1) were used to extract the radiomics features, the R software (version 4.1.1) was used to screen the radiomics features, and the variance method, Pearson correlation analysis, one-way COX analysis and random survival forest model were used to screen important radiomics features and calculate the Radiomics score (Radscore). X-tile software (version 3.6.1) was used to determine the best cut-off value of Radscore, and COX proportional hazard regression model was used to analyze the independent factors affecting the prognosis of patients. The training set data were imported into R software (version 4.1.1) to construct a clinical radiomics nomogram model of survival prediction for GBC. Based on the Radscore and the independent clinical factors affecting the prognosis of patients, the Radscore risk model and the clinical model for predicting the survival of GBC were constructed respectively. The C-index, calibration plot and decision curve analysis were used to evaluate the predictive ability of different survival prediction models for GBC. Observation indicators: (1) segmentation results of portal venous phase images in CT examination of GBC; (2) radiomic feature screening and Radscore calculation; (3) prognostic factors analysis of patients after curative-intent radical resection of GBC; (4) construction and evaluation of different survival prediction models for GBC. Measurement data with normal distribution were represented by Mean± SD. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed using the COX proportional hazard regression model. The postoperative overall survival rate was calculated by the life table method. Results:(1) Segmentation results of portal venous phase images in CT examination of GBC: the Dice similarity coefficient of the ROI based on the manual segmentation and nnU-Net segmentation models was 0.92±0.08 in the training set and 0.74±0.15 in the test set, respectively. (2) Radiomic feature screening and Radscore calculation: 1 502 radiomics features were finally extracted from 168 patients. A total of 13 radiomic features (3 shape features and 10 high-order features) were screened by the variance method, Pearson correlation analysis, one-way COX analysis and random survival forest model. Results of random survival forest model analysis and X-tile software analysis showed that the best cut-off values of the Radscore were 6.68 and 25.01. A total of 126 patients in the training set were divided into 41 cases of low-risk (≤6.68), 72 cases of intermediate-risk (>6.68 and <25.01), and 13 cases of high-risk (≥25.01). (3) Prognostic factors analysis of patients after curative-intent radical resection of GBC: the 1-, 2-, and 3-year overall survival rates of 168 patients were 75.8%, 54.9% and 45.7%, respectively. The results of univariate analysis showed that preopera-tive jaundice, serum CA19-9 level, Radscore risk (medium risk and high risk), extent of surgical resection, pathological T staging, pathological N staging, tumor differentiation degree (moderate differentiation and low differentiation) were related factors affecting prognosis of patients in the training set ( hazard ratio=3.28, 3.00, 3.78, 6.34, 4.48, 6.43, 3.35, 7.44, 15.11, 95% confidence interval as 1.91?5.63, 1.76?5.13, 1.76?8.09, 2.49?16.17, 2.30?8.70, 1.57?26.36, 1.96?5.73, 1.02?54.55, 2.04?112.05, P<0.05). Results of multivariate analysis showed that preoperative jaundice, serum CA19-9 level, Radscore risk as high risk and pathological N staging were independent influencing factors for prognosis of patients in the training set ( hazard ratio=2.22, 2.02, 2.89, 2.07, 95% confidence interval as 1.20?4.11, 1.11?3.68, 1.04?8.01, 1.15?3.73, P<0.05). (4) Construction and evaluation of different survival prediction models for GBC. Clinical radiomics model, Radscore risk model and clinical model were established based on the independent influencing factors for prognosis, the C-index of which was 0.775, 0.651 and 0.747 in the training set, and 0.759, 0.633, 0.739 in the test set, respectively. The calibration plots showed that the Radscore risk model, clinical model and clinical radiomics model had good predictive ability for prognosis of patients. The decision curve analysis showed that the prognostic predictive ability of the clinical radiomics model was better than that of the Radscore risk and clinical models. Conclusion:The clinical radiomics model based on the nnU-Net has a good predictive performance for prognosis of GBC.

Gastrointestinal characteristics of glycogen storage disease type Ⅰ in children / 中华实用儿科临床杂志

Objective:To investigate the gastrointestinal characteristics of children with glycogen storage disease (GSD) type Ⅰ.Methods:From June to December 2020, clinical data of children aged 0-18 years with GSD type Ⅰ diagnosed by genetic testing from all provinces and cities in China, including Beijing, Shanghai, Guangdong, Guangxi, Hunan, Sichuan, Yunnan, Guizhou, Henan, Hebei, Zhejiang, Jiangsu, Shaanxi, Anhui and Heilongjiang, were collected.A cross-sectional questionnaire survey was used for data analysis.Results:A total of 52 questionnaires were obtained, and 43 eligible patients aged 1-18 years were recruited, involving 30 males (69.8%) and 13 females (30.2%). Among them, 9 patients were GSD type Ⅰa and 34 patients were type Ⅰb.Seven patients (16.3%) had siblings who were also diagnosed as GSD type Ⅰb.The gastrointestinal manifestations included recurrent diarrhea in 26 patients (60.5%), perianal lesions (erythema, ulcer, abscess) in 25 patients (58.1%), abdominal pain/distension in 24 patients (55.8%), nausea/vomiting in 22 patients (51.1%), mucus/bloody stool in 14 patients (32.6%). Thirty-three patients (76.7%) had recurrent stomatitis and oral ulcer, and 38 patients (88.0%) had at least two gastrointestinal symptoms.White blood cell (WBC) count was <4.0×10 9/L in 24 patients (55.8%), and absolute neutrophils count was <1.5×10 9/L in 19 patients (44.2%), which was <0.5×10 9/L in 10 patients (23.3%). WBC count and absolute neutrophils count both decreased in children with GSD type Ⅰb.Platelets were >300×10 9/L in 30 patients (69.8%). Eighteen patients with GSD type Ⅰb underwent gastroscopy and colonoscopy, and 16 patients were diagnosed with GSD-related inflammatory bowel disease.Thirty-nine patients (90.7%) were fed with raw corn starch, 3 patients (6.9%) with maltodextrin and 19 patients (44.2%) with special enteral formula.Twenty patients with type Ⅰb GSD needed repeated antibiotic treatment due to neutropenia and neutrophil dysfunction.Fifteen patients were treated with granulocyte colony-stimulating factor (G-CSF). Among them, 11 patients were diagnosed as GSD-related bowel disease. Conclusions:Children with GSD type Ⅰ commonly have gastrointestinal symptoms, especially those with GSD type Ⅰb.The incidence of GSD-related inflammatory bowel disease is high in those children.G-CSF treatment cannot prevent the development of GSD-associated inflammatory bowel disease and its pathogenesis needs further research.Diet therapy is the first-line treatment of GSD type Ⅰ.Multidisciplinary management is helpful to reduce the complications and improve the quality of life in children with GSD type Ⅰ.

The effect of Pit-Crew cardiopulmonary resuscitation on the quality of chest compression / 中华急诊医学杂志

Objective:To observe the effect of team resuscitation with Pit-Crew cardiopulmonary resuscitation (CPR) mode on improving the quality of chest compression.Methods:A control method was conducted in this study. Sixty-four medical staffs in ICU and Emergency departments were divided into the role division group and non-role division group according to the ratio of doctors to nurses, with 8 teams in each group and 4 staffs in each team. A team leader was appointed in each team of the role division group to organize and coordinate the whole CPR process, and the non-role division group was not appointed. Each team performed chest compression for 8 min according to the recommendations of the 2020 AHA CPR Guideline under the monitoring of the CPR quality tracking system using a resuscitation manikin. CPR time, chest compression fraction (CCF), times of pressing interruption, times of pressing exceeding standard interruption (>10 s), pressing frequency, chest full recoil rate and other parameters were observed and recorded. The computer system recorded the above parameters, Student's t test and Mann-Whitney U test were used to compare the differences of indexes between the two groups. Results:After the training, the role division group achieved higher CCF [(69.13±1.55)% vs. (59.13 ± 6.08)%, P<0.05], and the total time was significantly shorter and times of overshoot interruptions was significantly less in the role division group compared with the non-role division group [(79.88±28.76) s vs. (135.25±32.99) s; 4 (3, 5) times vs. 2 (1, 2) times respectively; P<0.01]. There were no statistical differences in the total time of CPR and interruption numbers ( P>0.05). In addition, there were also no statistically significant differences in the pressing total numbers, correct times, pressing frequency, pressing depth, and the full rebound times of compression, as well as the substandard indicators of compression such as pressing too fast, too slow, too deep and insufficient rebound times of compression (all P>0.05). Conclusions:Pit-Crew CPR mode with designated team leader contributes to the implementation of high quality CPR, and the monitoring of CPR quality parameters and the applying of real-time feedback system can effectively improve the quality of chest compression.

Fixation of anterior pelvic ring fracture with long reconstruction plate combined with MIPPO technique / 中国骨伤

OBJECTIVE@#To evaluate the efficacy of long reconstruction plate combined with minimally invasive percutaneous plate osteosynthesis(MIPPO) technique in the treatment of unstable pelvic anterior ring fractures.@*METHODS@#From January 2013 to February 2019, 16 patients with unstable pelvic fracture were treated, including 12 males and 4 females, aged from 20 to 60 years(mean 46.5 years). According to Tile classification, there were 4 cases of type B1, 6 cases of type B2, 4 cases of type C1 and 2 cases of type C2. The fracture of all patients was closed, and the time from injury to operation was 7 to 10 days with an average of 6.2 days. The operation time, intraoperative blood loss, fracture reduction quality, fracture healing time, complications and limb function during the final follow-up were evaluated in 16 patients.@*RESULTS@#All 16 patients were followed up for 12 to 23 months (mean 19.1 months). The operation time was 60 to 180 min (mean 107.8 min). The intraoperative blood loss was 120 to 600 ml (mean 368.1 ml). The fracture healing time was 12 to 20 weeks (mean 16.3 weeks). According to Matta criteria, the fracture reduction was excellent in 6 cases, good in 8 cases and fair in 2 cases. One patient suffered from lateral femoral cutaneous nerve injury during the operation, and the lateral thigh sensation decreased after operation, which recovered after 6 months. One patient had pain stimulated by internal fixation at the iliac fossa. The symptoms were improved after the internal fixation was removed. The fractures of 16 patients were healed satisfactorily and there was no internal fixation loosening. Majeed score at the final follow-up was 67 to 95, excellent in 10 cases, good in 4 cases and fair in 2 cases.@*CONCLUSION@#Closed reduction and fixation of pelvic anterior ring fracture with long reconstruction plate combined with MIPPO technique through anterior approach has the advantages of less injury, less bleeding time during operation, saving operation time, high intraoperative safety, high fracture healing rate, early functional exercise after operation, and effective treatment of pelvic anterior ring fracture.

Plant Pharmacophylogeny: Review and Future Directions / 中国结合医学杂志

Medicinal plants have provided numerous medicinal active ingredients for thousands of years and these ingredients have been used in Chinese medicine (CM) and traditional pharmacologies worldwide. Recently, the exploitation and utilisation of medicinal plant resources has increased significantly. The results of the studies have led to the identification of many active components, such as steroidal alkaloids, saponins, terpenoids, and glycosides, in various medicinal plants with different evolutionary levels. Moreover, research on the chemical classification, molecular phylogeny, and pharmacological activity of medicinal plants is increasing in popularity. Pharmacophylogeny is an interdisciplinary topic that studies the correlation between plant phylogeny, chemical composition, and curative effects (pharmacological activity and the traditional curative effect) of medicinal plants. In addition, it provides the basic tools to enable research and development of CM resources. This literature review, based on the genetic relationship between phytogroup and species, highlights the formation process, research content, applications, and future directions of pharmacophylogeny.

Identification of serological biomarkers for diagnosis of rheumatoid arthritis using a protein array-based approach / 南方医科大学学报

OBJECTIVE@#To study the cytokine patterns in patients with rheumatoid arthritis (RA) and healthy individuals and identify candidate serum biomarkers for clinical diagnosis of RA.@*METHODS@#This study was conducted among 59 patients diagnosed with RA in our hospital from 2015 to 2019 with 46 age- and gender-matched healthy subjects who received regular physical examinations in our hospital as the control group. Serological autoimmune profiles of 5 RA patients and 5 healthy control subjects were obtained from human cytokine microarrays. We selected 4 differentially expressed cytokines (LIMPII, ROBO3, Periostin and IGFBP-4) and 2 soluble cytokine receptors of interest (2B4 and Tie-2) and examined their serum levels using enzyme-linked immunosorbent assay in 54 RA patients and 41 healthy control subjects. Spearman correlation test was performed to assess the correlation of serum cytokine and soluble receptor expression levels with the clinical features including rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score (DAS28) and health assessment questionnaire (HAQ). Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic capability of these cytokines.@*RESULTS@#We identified 6 dysregulated cytokines and soluble receptors (2B4, LIMPII, Tie-2, ROBO3, periostin and IGFBP-4) in RA patients (P < 0.01). The serum levels of LIMPII, ROBO3 and periostin were significantly correlated with the disease activity indicators including RF (P < 0.001), CRP (P < 0.001), DAS28 (P < 0.001) and HAQ (P < 0.001) in RA patients. Among the 6 candidate cytokines, 2B4 showed the largest area under the curve (AUC) of 0.861 for RA diagnosis (P < 0.001), followed then by LIMPII, ROBO3, periostin, Tie-2 and IGFBP-4.@*CONCLUSION@#Serum levels of LIMPII, ROBO3 and periostin can be indicative of the disease activity of RA, and serum 2B4, LIMPII, periostin, ROBO3, IGFBP-4 and Tie-2 levels may serve as biomarkers for the diagnosis of RA.

Paratesticular liposarcoma: the clinicopathological features of nineteen cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and differential diagnoses of paratesticular liposarcoma. Methods: The cases were collected from 2012-2020, from the archives of the Department of Pathology, Peking University Third Hospital, with diagnosis confirmed by histology, immunostaining and FISH tests. Results: Totally 19 patients were enrolled (including 11 in-hospital patients and 8 consultant cases). The patients aged 37-84 years (mean 57 years). The preoperative clinical diagnoses were spermatic cord/inguinal masses (nine patients), scrotal masses (seven patients), and inguinal hernia (three patients). Six lesions recurred after local resection, including one case extending from pelvic liposarcoma. Histologically, there were 10 cases of well-differentiated liposarcoma (WDLPS) and nine cases of dedifferentiated liposarcoma (DDLPS). WDLPSs mostly showed the combined features of lipoma-like, inflammatory and sclerosing subtypes (six patients); the other four WDLPSs had pure lipoma-like subtype features. DDLPSs were low-grade (three patients) or high-grade (six patients), with the morphology resembling myxofibrosarcoma, inflammatory myofibroblastoma, spindle cell sarcoma, pleomorphic undifferentiated sarcoma and pleomorphic liposarcoma. Intense inflammatory cells infiltration was commonly observed in five WDLPSs and two DDLPSs. Ossification was observed in three tumors. Immunohistochemically, the tumors were positive for MDM2 (8/10) and CDK4 (10/10), which were expressed in lipo-differentiating cells, spindle cells in WDLPS, and in dediffferentiated components. S-100 was only expressed by lipocytes (10/10). CD34 expression was positive and diffuse in the stromal cells of WDLPSs and focal or diffuse in dedifferentiated areas (10/10). FISH tests with an MDM2 gene probe were positive (12/12). Conclusions: Paratesticular liposarcoma may be overlooked by both clinicians and pathologists. WDLPS and DDLPS predominate, showing various histologic divergences. The presence of amplification of the 12q14-q15 region (containing the MDM2 and CDK4 genes) is helpful for making the correct diagnosis.