Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review

SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).@*METHODS@#The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.@*RESULTS@#The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.@*CONCLUSION@#Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

Relationship between self-reported occupational noise exposure and expression levels of plasma inflammatory cytokines in adult asthmatic patients / 公共卫生与预防医学

Objectives To investigate the relationship between self-reported occupational noise exposure and levels of plasma inflammatory cytokines in asthmatic patients. Methods A total of 910 adult asthmatic patients were selected as the study subjects, and their occupational noise exposure history and other related information were collected. The peripheral blood samples were collected from the patients, and the expression levels of plasma soluble CD14 (sCD14), complement factor D (CFD), Eotaxin-11 (CCL11), and IL-9 were determined. The relationship between self-reported occupational noise exposure and the expression levels of the four inflammatory cytokines in patients’ plasma were analyzed using multiple linear regression models. The interactions between confounding factors and self-reported occupational noise exposure were further analyzed by interaction analysis. Results The plasma CCL11, sCD14 and CFD expressions in asthmatic patients with self-reported occupational noise exposure were significantly higher than those in patients without the exposure (P<0.05). After adjusting for confounding factors, compared with patients reporting no occupational noise exposure, the plasma CFD expression was increased by 0.17 (95% CI: 0.02, 0.31) natural logarithm units in patients with self-reported occupational noise exposure. During remission, the levels of plasma CCL11 and sCD14 in asthmatic patients with self-reported occupational noise exposure were increased by 0.27 (95% CI: 0.05, 0.49) and 0.22 (95% CI: 0.02, 0.41) natural logarithm units, respectively, when compared with patients without the exposure. Interaction analysis showed that self-reported occupational noise exposure had significant multiplicative interaction with smoking or pet ownership on plasma CCL11 or CFD expressions in asthmatic patients (all P<0.05). Conclusion Self-reported occupational noise exposure is significantly associated with increased expression levels of plasma CFD, CCL11, and sCD14 in adult asthmatic patients.

Study on relationship of target organ injury of mechanism and "structure-effect-dose" of Hedysari Radix during radiotherapy-chemotherapy induced / 中国药理学通报

Aim To explore the possible mechanism of "component-target-pathway" of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy, and to verify the " dose-effect" relationship of the main active components. Methods TCMSP, Uniprot, Swiss Target Prediction, GeneCards, Cytoscape, Omicshare and other platforms were used for network pharmacology analysis. Autodock, Pymol and Ligplot were used for molecular docking. The water extract of Radix Hedysari was used for animal experiment verification. The contents of eight main components were determined by HPLC. Results Four active components, eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy. Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1, naringenin and MAPK3, and ursolic acid and TP53. Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly, liver and kidney factors Cr, BUN, AST and ALT decreased significantly, inflammatory factor IL-10 increased significantly and TNF-a decreased significantly. The content of ononm was the highest (2 . 884 8 µg • g "

Network meta-analysis of triple therapy for the prevention and treatment of acute nausea and vomiting caused by emetogenic chemotherapy drugs with moderate and high risk / 中国药房

OBJECTIVE To evaluate the efficacy of the triple therapy of 5-HT3 receptor antagonists， neurokinin-1 receptor antagonists and dexamethasone （referred to as “triple therapy”） in the prevention and treatment of acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） about triple therapy or 5-HT3 receptor antagonist combined with dexamethasone （referred to as “dual therapy”） were collected during the inception to May 2023. After literature screening， data extraction and literature evaluation， network meta-analysis was performed by using Stata 16.0 software. RESULTS A total of 59 RCTs were included， involving 23 418 patients and 15 interventions. Results of network meta-analysis showed that fosaprepitant + palonosetron + dexamethasone （FPD） was most effective in terms of acute nausea and vomiting control rate， followed by fosaprepitant + granisetron + dexamethasone （FGD） and aprepitant + ramosetron + dexamethasone （AMD）. In terms of acute nausea control rate， FPD was the most effective， followed by aprepitant + palonosetron + dexamethasone （APD） and FGD. In terms of acute vomiting control rate， FPD was the most effective， followed by FGD and APD. CONCLUSIONS Fosaprepitant + palonosetron + dexamethasone is better than other triple therapy or dual therapy in preventing acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs.

Intervention effect of 12 week spinal health gymnastics on high and low shoulder exercise in adolescents / 中国学校卫生

Objective@#To explore the intervention effect of 12 week spinal health exercise on adolescents high and low shoulders, in order to provide empirical evidence for exploring simple and feasible measures to intervene.@*Methods@#In February 2023, 60 high and low shoulder students from a vocational high school in a certain county of Luzhou City were randomly selected as the research subjects by convenient sampling method. Paired sampling was used to randomly divide participants into an intervention group and a control group with 30 students each group. The intervention group received spinal health gymnastics intervention during 12 weeks of morning exercises and large break exercises for twice a day, with two groups each time; the control group maintained their previous morning exercises and large break exercises. A follow up study was conducted on the height difference between the left and right shoulder peaks of the intervention group and the control group students before intervention, after 12 weeks intervention, at 4 weeks post intervention. The t-test was used to analyze the changes in shoulder peak height difference between the intervention group and the control group.@*Results@#Before intervention, there was no statistically significant difference in the height of the left and right shoulder peaks between the intervention group [(2.50±1.19)cm] and the control group [(2.49±1.20)cm] adolescents ( t=0.05, P > 0.05). After 12 weeks of intervention, the difference in shoulder height between the left and right sides of adolescents in the intervention group decreased, compared to that before intervention [(1.43±1.15, 2.50±1.19)cm], while the control group increased compared to that before intervention [(2.58±1.19, 2.49±1.20) cm], and the differences were both statistically significant ( t= -78.17 , 20.15, P <0.05). At 4 weeks post intervention, there was no statistically significant difference in the height of the left and right shoulder peaks between the intervention group [(1.44±1.15)cm] and the control group [(2.59±1.18)cm] compared to 12 weeks after the intervention ( t=1.80, 1.05, P >0.05). The intervention group [(2.49±1.26, 2.52±1.16) (1.43±1.21, 1.44±1.13) (1.44±1.21, 1.45±1.14)cm] and the control group [(2.45±1.24, 2.52±1.20) (2.55±1.24, 2.61±1.18) (2.55±1.22, 2.62±1.18)cm] showed no statistically significant difference in the height of the left and right shoulder peaks between males and females before intervention, after 12 weeks of intervention, and after stopping intervention for 4 weeks ( t =-0.08, -0.03, -0.02; -0.15, -0.12, -0.15, P >0.05).@*Conclusions@#Spinal health gymnastics has a good effect on correcting high and low shoulders in adolescents. Spinal health gymnastics should be promoted on campus to promote adolescent posture health.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition) / 中草药·英文版

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Three-dimensional finite element study on the effects of maxillary anterior two-step retraction and en-masse retraction with clear aligners / 中华口腔医学杂志

Objective: To investigate the effects of two-step retraction and en-masse retraction on tooth movement pattern of anterior teeth and posterior anchorage with clear aligners using three-dimensional finite element analysis. Methods: A finite element model of maxillary first premolar extraction case undergoing clear aligner treatment was established based on maxillofacial cone-beam CT data of a 24-year-old adult male with individual normal occlusion, who visited Department of Oral Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine for impacted mandibular third molar in June, 2022. The initial tooth displacement of five anterior retraction protocols (two-step with canine retraction, two-step with incisor bodily retraction, two-step with incisor retraction-overtreatment, en-masse bodily retraction, and en-masse retraction-overtreatment) were evaluated. Results: Two step with canine retraction caused distal tipping of the canine and labial tipping of the incisors (0.18° for central incisor and 0.13° for lateral incisor). Two step with incisor retraction caused mesial tipping of the canine. In two step with bodily retraction protocol, uncontrolled lingual tipping was found in central incisor (0.29°) and lateral incisor (0.32°). In two-step with incisor retraction-overtreatment protocol, the movement pattern of the incisors didn't change, but the inclinations reduced to 0.21° and 0.18°. En-masse retraction caused distal tipping of the canine. In en-masse bodily retraction protocol, uncontrolled lingual tipping was also found in central incisor (0.19°) and lateral incisor (0.27°). In en-masse retraction-overtreatment protocol, the central incisor showed controlled lingual tipping (0.02°) and the lateral incisor showed palatal root movement (0.03° labial inclination). Posterior teeth exhibited mesial tipping in all five protocols. Conclusion: En-masse retraction with incisor overtreatment was beneficial to incisor torque control in clear aligner treatment.

Determination of cobalt and tungsten in human urine by inductively coupled plasma mass spectrometry / 中华劳动卫生职业病杂志

Objective: To establish a inductively coupled plasma mass spectrometry method for the determination of trace cobalt and tungsten in human urine. Methods: The authors used 1% nitric acid solution as diluent in October-December 2021, the sample dilution factor and internal standard element were optimized by single factor rotation experiment, and the difference between the working curve and the standard curve was compared. Results: The method uses working curve to determine cobalt and tungsten in urine, the linear range of this method was 0.0~10.0 μg/L, the correlation coefficient was 0.999 9, the detection limits respectively were 0.005 μg/L (cobalt) and 0.09 μg/L (tungsten), the recoveries of samples respectively were 87.0%~100.2% (cobalt) and 89.4%~104.8% (tungsten), the relative standard deviations respectively were 0.4%~4.4% (cobalt) and 0.6%~3.8% (tungsten) . Conclusion: A simple and rapid method for determination of cobalt and tungsten in urine has been established. This method has the advantages of simple operation, high sensitivity, low detection limit and good stability. It is suitable for determination of cobalt and tungsten in urine of all kinds of people.

Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy / 中华肿瘤杂志

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Prediction of new atrial fibrillation after off-pump coronary artery bypass grafting based on preoperative heart rate variability: A retrospective study / 中国胸心血管外科临床杂志

@#Objective    To study the relationship between preoperative heart rate variability (HRV) and postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass grafting (OPCAB). Methods    A retrospective analysis was performed on the clinical data of 290 patients who were admitted to the Department of Cardiovascular Surgery, General Hospital of Northern Theater Command from May to September 2020 and received OPCAB. There were 217 males and 73 females aged 36-80 years. According to the incidence of POAF, the patients were divided into two groups: a non-atrial fibrillation group (208 patients) and an atrial fibrillation group (82 patients). The time domain and frequency domain factors of mean HRV 7 days before operation were calculated: standard deviation of all normal-to-normal intervals (SDNN), root mean square of successive differences, percentage difference between adjacent normal-to-normal intervals that were greater than 50 ms, low frequency power (LF), high frequency power (HF), LF/HF. Results    The HRV value of patients without POAF was significantly lower than that of patients with POAF (P<0.05). The median SDNN of the two groups were 78.90 ms and 91.55 ms, respectively. Age (OR=3.630, 95%CI 2.015-6.542, P<0.001), left atrial diameter (OR=1.074, 95%CI 1.000-1.155, P=0.046), and SDNN (OR=1.017, 95%CI 1.002-1.032, P=0.024) were independently associated with the risk of POPAF after OPCAB. Conclusion     SDNN may be an independent predictor of POAF after OPCAB.

Long-term effectiveness of uncemented allograft-prosthesis composite for reconstruction of bone defects after proximal femur tumor resection / 中国修复重建外科杂志

OBJECTIVE@#To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection.@*METHODS@#Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded.@*RESULTS@#All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients.@*CONCLUSION@#Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.

A Dataset on the Dynamic Monitoring of Health and Family Planning of China's Internal Migrants: A Multi-Wave Large-Scale, National Cross-Sectional Survey from 2009 to 2018 / 中国医学科学杂志(英文版)

This data article presents data from the China Migrants Dynamic Survey (CMDS), a multi-wave, large-scale national cross-sectional survey of China's internal migrants from 2009 to 2018. The CMDS is an annual questionnaire survey conducted by the former National Health and Family Planning Commission (NHFPC) of the People's Republic of China. The respondents included in this survey are internal migrants over 15 years old. The sample was drawn from the China Migrant Population Information System, using multi-stage stratified sampling method and the probability proportional-to-size (PPS) cluster sampling strategy. Between 2009 and 2018, there were 1,527,650 internal migrants from 23 provinces, 5 autonomous regions and 4 municipalities participated in the surveys. The survey tools were a series of self-designed questionnaires with high inheritance and consistency designed and implemented by the NHFPC. The questionnaires mainly contain basic information of the respondents and their family members, migration status, healthcare or health behaviors, public health service utilization, social insurance, social integration, and family planning. The dataset is currently the most widely used survey data on China's internal migrants, offering information on migration patterns, healthcare and health behaviors, use of public health services, access to social security, social integration, and family planning, which are valuable for health planning, health decision-making, and health equity research.

Research progress in microevolutionary process of excellent traits and quality of Dao-di herbs / 中国中药杂志

Dao-di herbs are the treasure of Chinese materia medica and one of the characteristic research objects of traditional Chinese medicine(TCM). Probing into the microevolution of Dao-di herbs can help to reveal their biological essence and quality formation mechanisms. The progress in molecular biology and omics provides the possibility to elucidate the phylogenetic and quality forming characteristics of Dao-di herbs at the molecular level. In particular, genomics serves as a powerful tool to decipher the genetic origins of Dao-di herbs, and molecular markers have been widely used in the research on the genetic diversity and population structure of Dao-di herbs. Focusing on the excellent traits and quality of Dao-di herbs, this paper reviews the studies about the microevolution process of quality formation mechanisms of Dao-di herbs with the application of molecular markers and omics, aiming to underpin the protection and utilization of TCM resources.

Research and development practice of traditional Chinese medicine based on network target theory and technology / 中国中药杂志

Network targets theory and technology have transcended the limitations of the "single gene, single target" model, aiming to decipher the mechanisms of traditional Chinese medicine(TCM) based on biological network from the perspective of informatics and system. As the core of TCM network pharmacology, with the development of computer science and high-throughput experimental techniques, the network target theory and technology are beginning to exhibit a trend of organic integration with artificial intelligence technology and high-throughput multi-modal multi-omics experimental techniques. Taking the network target analysis of TCM like Yinqiao Qingre Tablets as a typical case, network target theory and technology have achieved the systematic construction, in-depth analysis, and high-throughput multi-modal multi-omics validation of multi-level biological networks spanning from traditional Chinese and Western phenotypes to tissues, cells, molecules, and traditional Chinese and Western medicines. This development helps to address critical issues in the analysis of mechanisms of TCM, including the discovery of key targets, identification of functional components, discovery of synergistic effects among compound ingredients, and elucidation of the regulatory mechanisms of formulae. It provides powerful theoretical and technological support for advancing clinical precision diagnosis and treatment, precise positioning of TCM, and precise research and development of TCM. Thus, a new paradigm of TCM research gradually emerges, combining big data and artificial intelligence(AI) with the integration of human experience and scientific evidence.

Advances in research and application of Trichoderma for inducing resistance against root rot diseases in root and rhizome of Chinese medicinal materials / 中国中药杂志

Root rot is a microbial disease that is difficult to control and can result in serious losses in the planting of most Chinese medicinal materials. As high as 87.6% of roots or rhizomes of Chinese medicinal materials are susceptible to root rot, which seriously affects the cultivation development of Chinese medicinal materials. Trichoderma fungi, possessing biological control functions, can induce plants to improve their resistance to microbial diseases, promote plant growth, and effectively reduce the losses caused by various microbial diseases on cultivation. At present, Trichoderma is rarely used in the cultivation of Chinese medicinal materials, so it has great application potential for the prevention and control of root rot diseases in farmed Chinese medicinal materials. Based on the above situation, after comparison and discussion, it is believed that compared with chemical control and physical control, biological control of root rot diseases of Chinese medicinal materials is more efficient and meets the development needs of Chinese medicinal materials ecological planting in China. This paper reviewed the progress in the research and application of Trichoderma in the control of root rot diseases in the root and rhizome of farmed Chinese medicinal materials in the past 10 years and found that most of the current research on the biological control of root rot diseases in Chinese medicinal materials was mostly limited to the verification of the inhibitory effect of Trichoderma strains on the growth of the pathogenic microbes. Studies on the induction effect of Trichoderma on Chinese medicinal materials are not in depth. Studies on the responding mechanisms of most Chinese medicinal materials to Trichoderma are highly absent. Moreover, there are few reports on field experiments, which indicates that there is a long way to go before Trichoderma is widely applied in the farming practice of Chinese medicinal materials. To sum up, this paper aimed to link the present and the future and advocated further relevant research and more experiments on the application of Trichoderma in the farming of Chinese medicinal materials.

Universal chimeric Fcγ receptor T cells with appropriate affinity for IgG1 antibody exhibit optimal antitumor efficacy

Developing universal CARs with improved flexible targeting and controllable activities is urgently needed. While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells, the weak affinity between them is one of the limiting factors for efficacy. Herein, we systematically investigated the impact of Fcγ receptor (FcγR) affinity on CAR-T cells properties by constructing universal CARs using Fcγ receptors with different affinities for IgG1 antibodies, namely CD16a, CD32a, and CD64. We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies. In xenografted mice, 64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model. However, in the CD20 high expression Raji model, 64CAR caused excessive activation of CAR-T cells, which resulted in cytokine release syndrome (CRS) and the decline of antitumor activity, and 32CAR with a moderate affinity brought the best efficacy. Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.

Seven new 3,4-dihydro-furanocoumarin derivatives from Angelica dahurica / 中草药·英文版

OBJECTIVE@#To study the chemical constituents of the roots of Angelica dahurica, a well-known Chinese herbal medicine named Baizhi in Chinese.@*METHODS@#Compounds were separated by various chromatographies, and the structures of new compounds were elucidated based on the analysis of their spectroscopic and spectrometric data (1D, 2D NMR, HRESI MS, IR, and UV). The absolute configurations of new compounds were determined by the calculated electronic circular dichroism and chemical derivatization. The inhibitory activities of all isolates against nitric oxide (NO) production were evaluated using lipopolysaccharide-activated RAW 264.7 macrophage cells.@*RESULTS@#Seven new 3,4-dihydro-furanocoumarin derivatives ( 1a/ 1b, 2a/ 2b, 3a/ 3b, 4) together with a known furanocoumarin ( 5) were isolated from the roots of A. dahurica. The new compounds included three pairs of enantiomers, (4S, 2''R)-angelicadin A ( 1a)/(4R, 2''S)-angelicadin A ( 1b), (4S, 2''S)-angelicadin A ( 2a)/(4R, 2''R)-angelicadin A ( 2b), and (4S, 2''S)-secoangelicadin A ( 3a)/(4R, 2''R)-secoangelicadin A ( 3b), together with (4R, 2''R)-secoangelicadin A methyl ester ( 4). The known xanthotoxol ( 5) inhibited the NO production with the half-maximal inhibitory concentration (IC50) value of (32.8 ± 0.8) µmol/L, but all the new compounds showed no inhibitory activities at the concentration of 100 µmol/L.@*CONCLUSION@#This is the first report of the discovery of 3,4-dihydro-furanocoumarins from A. dahurica. The results are not only meaningful for the understanding of the chemical constituents of A. dahurica, but also enrich the reservoir of natural products.

Feasibility and clinical benefits of the double-ProGlide technique for hemostasis after cryoballoon atrial fibrillation ablation with uninterrupted oral anticoagulants / 老年心脏病学杂志（英文版）

OBJECTIVE@#To access the efficacy and safety of the double-ProGlide technique for the femoral vein access-site closure in cryoballoon ablation with uninterrupted oral anticoagulants (OAC), and its impact on the electrophysiology laboratory time as well as hospital stay after the procedure in this observational study.@*METHODS@#Patients with atrial fibrillation undergoing cryoballoon ablation with uninterrupted OAC at Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China from May 2019 to May 2021 were enrolled in this study. From October 2020, double-ProGlide technique was consistently used for hemostasis (ProGlide group), and before that conventional manual compression was utilized (manual compression group). The occurrence of vascular and groin complications was accessed during the hospital stay and until the three-month follow-up.@*RESULTS@#A total of 140 participants (69.30% of male, mean age: 59.21 ± 10.29 years) were evaluated, 70 participants being in each group. Immediate hemostasis was achieved in all the patients with ProGlide closure. No major vascular complications were found in the ProGlide group while two major vascular complications were occurred in the manual compression group. The incidence of any groin complication was obviously higher in subjects with manual compression than patients with ProGlide devices (15.71% vs. 2.86%, P = 0.009). In addition, compared with the manual compression group, the ProGlide group was associated with significantly shorter total time in the electrophysiology laboratory [112.0 (93.3-128.8) min vs. 123.5 (107.3-158.3) min, P = 0.006], time from sheath removal until venous site hemostasis [3.8 (3.4-4.2) min vs. 8.0 (7.6-8.5) min, P < 0.001], bed rest time [8.0 (7.6-8.0) h vs. 14.1 (12.0-17.6) h, P < 0.001] and hospital stay after the procedure [13.8 (12.5-17.8) h vs. 38.0 (21.5-41.0) h, P < 0.001].@*CONCLUSIONS@#Utilization of the double-ProGlide technique for hemostasis after cryoballoon ablation with uninterrupted OAC is feasible and safe, which has the clinical benefit in reducing the total electrophysiology laboratory time and the hospital stay length after the procedure.

Study on environmental residues detection and cleaning method of 15 cytotoxic antineoplastic drugs in PIVAS of our hospital / 中国药房

OBJECTIVE To provide a method to reduce environmental residues for pharmacy intravenous admixture service （PIVAS）， and ensure the occupational health of medical staff. METHODS The residues of 15 cytotoxic antineoplastic drugs such as gemcitabine were detected by UPLC-Q-Orbitrap-HRMS. The cleaning process was optimized with the residual quantity as the index. Nitrogen blowing method was used for alcohol volatilization experiment. CCK-8 assay was used to detect the effect of chlorine-containing disinfectant on the toxicity of cytotoxic antitumor drugs. RESULTS The linear range of 15 cytotoxic antineoplastic drugs such as gemcitabine were 0.5-1 000 ng/mL. RSDs of intra-day and intra-day precision were no higher than 20.00%. Six drugs including gemcitabine， isocyclophosphamide and cyclophosphamide were detected in the PIVAS environment of our hospital， and the residue of cyclophosphamide was relatively high. The optimal cleaning procedure was cleaning once with water + cleaning once with 1 000 mg/L chlorine-containing disinfectant + cleaning once with 75% alcohol， wiping with dry gauze method. The results of alcohol volatilization test showed that there was no significant difference in drug residues between control group and 75% alcohol group （P＞0.05）. The results of CCK-8 test showed that compared with control group， the survival rates of the cells treated with 15 cytotoxic antineoplastic drugs were decreased significantly （P＜0.01）； the survival rates of the cells treated with 15 cytotoxic antineoplastic drugs+chlorine-containing disinfectant were significantly higher than those treated with 15 cytotoxic antineoplastic drugs （P＜0.01）. CONCLUSIONS A method for the simultaneous determination for residues of 15 cytotoxic antineoplastic drugs such as gemcitabine in PIVAS is successfully established； the optimal cleaning procedure can significantly reduce the residues of drugs， the use of chlorine- containing disinfectant can significantly reduce the toxicity of drug， and the residual drugs will not cause secondary contamination of the operating area with alcohol volatilization.