Nutritional Status of Children Aged 3 to 7 Years in Zhag′yab， Tibet / 中山大学学报(医学科学版)

ObjectiveTo understand the physical development level of 3-7 years old children in Zhag′yab， and to provide reference for local health decision-making. MethodsA cross-sectional study was conducted between June 2021 and July 2021， with a sample of 1 247 Tibetan children aged 3-7 years from kindergartens in 13 districts of Zhag′yab. Their height and weight were measured and the hemoglobin was detected by a unified method. Standard statistical method was adopted （Z-score method）. Z-scores of length /height-for-age （HAZ）， Z-scores of weight-for-age （WAZ）， Z-scores of body mass index （BMI）-for-age （BAZ） and Z-scores of weight-for-height （WHZ） were calculated by WHO Anthro v3.2.2 and WHO Anthro Plus. The nutritional status of children was evaluated according to WHO diagnostic criteria for malnutrition and anemia. ResultsThe average WAZ and HAZ of children aged 3 to 7 in Zhag′yab were lower than the WHO standards，except for the WAZ of 4-year old， the differences were statistically significant （P<0.05）. The overall detection rate of malnutrition was 25.7%， stunting， underweight， wasting， overweight， obesity and anemia were 11.6%， 11.8%， 10.8%， 3.3%， 1.8% and 29.3%， respectively. The detection rates of all indicators in boys were higher than those in girls， and the differences were not statistically significant （P>0.05）. The overweight rate and obesity rate of rural children were lower than those of urban children， and the other detection rates were higher than those of urban children. The differences of underweight rate， obesity rate and anemia rate were statistically significant between urban and rural children （P<0.05）. Among the detection rates of all indicators in different age groups， there were statistically significant differences in the overweight rate and the anemia rate （P<0.05）. The overweight rate of children aged 4 and the anemia rate of children aged 5 were the highest. ConclusionsThe physical development of children aged 3 to 7 in Zhag′yab is poor， and the prevalence of malnutrition and anemia is high. Underweight and anemia are more serious in rural children， and the overweight and obesity problem of urban children is emerging. More attention should be paid to promote their nutritional status. The prevention and intervention of children’s malnutrition should be strengthened in Zhag′yab.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Epidemiological characteristics of norovirus acute gastroenteritis outbreaks and influencing factors in China, 2007-2021 / 中华流行病学杂志

Objective: To analyze the epidemiological characteristics of norovirus-caused acute gastroenteritis outbreaks in China, identify the factors influencing the scale of outbreaks, and provide scientific evidences for early control of norovirus infection outbreaks. Methods: The descriptive epidemiological analysis approach was applied to analyze the incidence of national norovirus infection outbreaks by using the data from the Public Health Emergency Event Surveillance System in China from January 1, 2007 to December 31, 2021. The unconditional logistic regression model was applied to analyze the risk factors that affected the outbreaks' scale. Results: A total of 1 725 norovirus infection outbreaks were recorded in China from 2007 to 2021, with an upward trend in the number of the reported outbreaks. The southern provinces had their annual outbreak peaks from October to March; the northern provinces had two outbreak peaks from October to December and from March to June annually. The outbreaks occurred mainly in southeastern coastal provinces with a trend of gradual spread to central, northeastern and western provinces. The outbreaks mainly occurred in schools and childcare setting (1 539 cases, 89.22%), followed by enterprises and institutions (67 cases, 3.88%) and community households (55 cases, 3.19%). Human to human transmission was the main infection route (73.16%), and norovirus GⅡ genotype was the predominate pathogen causing the outbreaks (899 cases, 81.58%). The time interval between the onset of the primary case and the outbreak reporting M (Q1, Q3) was 3 (2, 6) days and the case number of the outbreak M (Q1, Q3) was 38 (28, 62). The timeliness of outbreak reporting was improved in recent years and the scale of the outbreaks showed a decreasing trend over the years, the differences in reporting timeliness and outbreak scale among different settings were significant (P<0.001). The factors that affected outbreaks' scale included the outbreak setting, transmission route, outbreak reporting timeliness and type of living areas (P<0.05). Conclusions: From 2007 to 2021, the number of the norovirus-caused acute gastroenteritis outbreaks increased in China and the more areas were affected. However, the outbreak scale showed a decreasing trend and the outbreak reporting timeliness was improved. It is important to further improve the surveillance sensitivity and reporting timeliness for the effective control of the outbreak scale.

Epidemiological characteristics of typhoid fever and paratyphoid fever in China, 2004-2020 / 中华流行病学杂志

Objective: To analyze the incidence trend and epidemiological characteristics of typhoid fever and paratyphoid fever in China from 2004 to 2020, understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures. Methods: The descriptive epidemiological method and spatial analysis method were applied to analyze the epidemiological characteristics of typhoid fever and paratyphoid fever in China during this period by using the surveillance data collected from the National Notifiable Infectious Disease Reporting System of Chinese Center for Disease Control and Prevention. Results: A total of 202 991 cases of typhoid fever were reported in China from 2004 to 2020. More cases occurred in men than in women (sex ratio: 1.18∶1). Most cases were reported in adults aged 20-59 years (53.60%). The incidence rate of typhoid fever decreased from 2.54/100 000 in 2004 to 0.38/100 000 in 2020. The highest incidence rate was reported in young children aged <3 years after 2011, ranging from 1.13/100 000 to 2.78/100 000, and during this period the proportion of cases in this age group increased from 3.48% to 15.59%. The proportion of the cases in the elderly aged ≥60 years increased from 6.46% in 2004 to 19.34% in 2020. The hotspot areas existed in Yunnan, Guizhou, Guangxi and Sichuan Provinces and expanded to Guangdong, Hunan, Jiangxi, and Fujian Provinces. A total of 86 226 paratyphoid fever cases were reported from 2004 to 2020, the male to female ratio of the cases was 1.21∶1. Most cases were reported in adults aged 20-59 years (59.80%). The incidence rate of paratyphoid fever decreased from 1.26/100 000 in 2004 to 0.12/100 000 in 2020. The highest incidence rate of paratyphoid fever was in young children aged <3 years after 2007, ranging from 0.57/100 000 to 1.19/100 000, and during this period the proportion of the cases in this age group increased from 1.48% to 30.92%. The proportion of the cases in the elderly aged ≥60 years increased from 4.52% in 2004 to 22.28% in 2020. The hotspot areas expanded to the east, including Guangdong, Hunan and Jiangxi Provinces, from Yunnan, Guizhou, Sichuan, and Guangxi Provinces. Conclusions: The results showed a low level of incidence of typhoid fever and paratyphoid fever in China with a trend of decreasing per year. The hotspots were mainly in the of Yunnan, Guizhou, Guangxi and Sichuan Provinces, with an expanding trend to eastern China. It is necessary to strengthen the typhoid fever and paratyphoid fever prevention and control in southwestern China, among young children aged <3 years and the elderly aged ≥60 years.

Current research status and application prospect of numerical simulation in traditional Chinese medicine drying / 中国中药杂志

With the rapid development of computer technology, numerical simulation has gradually become an important method to study drying process and improve drying equipment. Using computer to simulate the drying process of traditional Chinese medicine(TCM) is characterized by intuitiveness, scientificity, and low cost, which serves as an auxiliary means for technical innovation in TCM drying. This paper summarizes the theories of different drying methods and the research status of numerical simulation in drying, introduces the modeling methods and software of numerical simulation, and expounds the significance of numerical simulation modeling in shortening the research and development cycle, improving drying equipment, and optimizing drying parameters. However, the current numerical simulation method for drying process has problems, such as low accuracy, lack of quantitative indicators for the control of simulation results on the process, and insufficient in-depth research on the mechanism of drug quality changes. Furthermore, this paper put forward the application prospect of numerical simulation in TCM drying, providing reference for the further study of numerical simulation in this field.

Effects of porcine urinary bladder matrix on motility and polarization of bone marrow-derived macrophages in mice / 中华烧伤杂志

Objective: To explore the effects of porcine urinary bladder matrix (UBM) on the motility and polarization of bone marrow-derived macrophages in mice, so as to provide evidence for the rational selection of stent in clinical wound repair. Methods: The method of experimental research was used. The microstructure of porcine UBM and absorbable dressing was observed under scanning electron microscope. Polyacrylamide gel electrophoresis was used to observe the protein distribution of the two stent extracts. The primary macrophages were induced from bone marrow-derived cells isolated from six 6-8-week-old male C57BL/6J mice (mouse age, sex, and strain, the same below) and identified. Three batches of macrophages were divided into porcine UBM extract group and absorbable dressing extract group. The cells in each group were cultured with Dulbecco's modified Eagle medium/F12 medium containing the corresponding extracts. The cell migration rate was detected and calculated on 1, 3, and 7 d after scratching by scratch test. The number of migrated cells at 12 and 24 h of culture was detected by Transwell experiment. The percentages of CD206 and CD86 positive cells at 24 h of culture was detected by flow cytometer. The numbers of sample in the above cell experiments were all 3. An incision was prepared on the left and right back of twelve mice, respectively. The left incision of each mouse was included in porcine UBM group and the right incision was included in absorbable dressing group, and the corresponding stents were implanted into the incisions respectively. On post operation day (POD) 7 and 14, the number of inflammatory cells infiltrated in the stent was detected by hematoxylin-eosin staining; the number of F4/80, transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and matrix metalloprotein-9 (MMP-9) positive cells and type Ⅰ collagen deposition in stents were observed by immunohistochemistry; the percentages of F4/80, CD86, and CD206 positive cells were observed by immunofluorescence staining. The numbers of sample in the above animal experiments were all 6. Data were statistically analyzed with analysis of variance for factorial design, analysis of variance for repeated measurement, and independent sample t test. Results: Porcine UBM has a dense basement membrane structure on one side and porous propria containing a fibrous structures on the other. Both sides of the absorbable dressing had three-dimensional porous structure. In the molecular weight range of (50-70)×103, multiple non-type Ⅰ collagen bands appeared in the lanes of porcine UBM extract, while no obvious bands appeared in the lanes of absorbable dressing extract. It had been identified that mouse bone marrow-derived cells had been successfully induced into macrophages. The cell migration rates in porcine UBM extract group were significantly higher than those in absorbable dressing extract group on 1, 3, and 7 d after scratching (with t values of 15.31, 19.76, and 20.58, respectively, P<0.05). The numbers of migrated cells in porcine UBM extract group were significantly more than those in absorbable dressing extract group at 12 and 24 h of culture (with t values of 12.20 and 33.26, respectively, P<0.05). At 24 h of culture, the percentage of CD86 positive cells in porcine UBM extract group ((1.27±0.19)%) was significantly lower than (7.34±0.14)% in absorbable dressing extract group (t=17.03, P<0.05);the percentage of CD206 positive cells in porcine UBM extract group was (73.4±0.7)%, significantly higher than (32.2±0.5)% in absorbable dressing extract group (t=119.10, P<0.05). On POD 7 and 14, the numbers of inflammatory cells infiltrated in the stents in porcine UBM group was significantly more than those in absorbable dressing group (with t values of 6.58 and 10.70, respectively, P<0.05). On POD 7 and 14, the numbers of F4/80, TGF-β1, VEGF, and MMP-9 positive cells in the stents in porcine UBM group were significantly more than those in absorbable dressing group (with t values of 46.11, 40.69, 13.90, 14.15, 19.79, 32.93, 12.16, and 13.21, respectively, P<0.05); type Ⅰ collagen deposition in the stents in porcine UBM group was more pronounced than that in absorbable dressing group; the percentages of CD206 positive cells in the stents in porcine UBM group were significantly higher than those in absorbable dressing group (with t values of 5.05 and 4.13, respectively, P<0.05), while the percentages of CD86 positive cells were significantly lower than those in absorbable dressing group (with t values of 20.90 and 19.64, respectively, P<0.05), and more M2-type macrophages were seen in the stents in porcine UBM group and more M1-type macrophages were seen in the stents in absorbable dressing group. Conclusions: Porcine UBM can enhance macrophage motility, induce M2 polarization and paracrine function, create a microenvironment containing growth factors such as TGF-β1 and MMP-9 tissue remodeling molecules, and promote tissue regeneration and extracellular matrix remodeling in mice.

The Latest Research Progress of Selinexor in the Treatment of Non-Hodgkin Lymphoma --Review / 中国实验血液学杂志

Non-Hodgkin lymphoma (NHL) is a common lymphoid hematological malignancy, the treatment and prognosis of NHL have always been the focus of clinical attention. Chemotherapy is the main first-line treatment, but there is still no effective treatment for patients with poor response to chemotherapy, recurrence or progression within a short period of time after treatment, and new and effective drugs need to be developed clinically. As the only clinically validated oral selective inhibitor of nuclear export (SINE), Selinexor has been approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma and multiple myeloma, clinical attempts are being made to apply it to the treatment of other hematological malignancies.This article reviews the anti-tumor mechanism of Selinexor and the latest research progress in its application in NHL, and provides ideas for a more diverse, standardized and effective applications of Selinexor in NHL.

Identification and verification of α-11 giardin-interacting protein / 中国血吸虫病防治杂志

Objective To identify and verify the interacting protein of α-11 giardin, so as provide the experimental evidence for studies on the α-11 giardin function. Methods The yeast two-hybrid cDNA library of the Giardia lambia C2 strain and the bait plasmid of α-11 giardin were constructed. All proteins interacting with α-11 giardin were screened using the yeast two-hybrid system. α-11 giardin and all screened potential interacting protein genes were constructed into pBiFc-Vc-155 and pBiFc-Vn-173 plasmids, and co-transfected into the breast cancer cell line MDA-MB-231. The interactions between α-11 giardin and interacting proteins were verified using bimolecular fluorescence complementation (BiFC). Results The yeast two-hybrid G. lambia cDNA library which was quantified at 2.715 × 107 colony-forming units (CFU) and the bait plasmid containing α-11 giardin gene without an autoactivation activity were constructed. Following two-round positive screening with the yeast two-hybrid system, two potential proteins interacting with α-11 giardin were screened, including eukaryotic translation initiation factor 5A (EIF5A), calmodulin-dependent protein kinase (CAMKL) and nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH), hypothetical protein 1 (GL50803_95880), hypothetical protein 2 (GL50803_87261) and a protein from Giardia canis virus. The α-11 giardin and EIF5A genes were transfected into the pBiFc-Vc-155 and pBiFc-Vn-173 plasmids using BiFC, and the recombinant plasmids pBiFc-Vc-155-α-11 and pBiFc-Vn-173-EIF5A were co-tranfected into MDA-MB-231 cells, which displayed green fluorescence under a microscope, indicating the interaction between α-11 giardin and EIF5A protein in cells. Conclusion The yeast two-hybrid cDNA library of the G. lambia C2 strain has been successfully constructed, and six potential protein interacting with α-11 giardin have been identified, including EIF5A that interacts with α-11 giardin in cells.

Rapid identification of chemical constituents in Xuezhikang Capsule by UPLC-Q-TOF/MSE combined with the establishment of UNIFI MS database / 药学学报

An UPLC-Q-TOF/MSE technology coupled with UNIFI database was used to develop a rapid, high coverage, accurate and efficient chemical composition qualitative method for Xuezhikang Capsule. A UNIFI database was established utilizing compound name, formula, structure, following automatic matching with high-resolution mass numbers, isotope distributions, mass deviations, fragment ion matching, and chromatographic retention features in UNIFI database to achieve the qualitative results of natural products in Xuezhikang Capsules. Combined with manual confirmation, 82 chemical components were identified in Xuezhikang Capsules, and the MS2 fragmentation pathway of typical organic acids, flavonoids, monacrines, and monascus were analyzed to ensure accuracy of the LC-MS workflow. This study clarified the chemical substance basis of Xuezhikang Capsules by LC-MS technology, providing experimental data support for the identification of key quality attributes, quality control and consistency evaluation in the manufacturing process of Xuezhikang Capsules.

Effects of carbonization processing on quality control, chemical compositions, and pharmacological mechanism of Ganjiang (Zingiberis Rhizoma) / 数字中医药（英文）

@#Ganjiang (Zingiberis Rhizoma, ZR) and Jiangtan (Carbonized Zingiberis Rhizoma, CZR) have long been used in traditional Chinese medicine (TCM) with a rich history in the treatment of various ailments. While ZR and CZR obviously stem from the same botanical source, their attributes, chemical compositions, pharmacological behaviors, and clinical applications are different owing to variations in the extent of drying and processing they undergo. In this paper, data pertaining to ZR and CZR were retrieved from databases including China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, and Google Scholar. These sources were scrutinized to elucidate the distinctions between ZR and CZR arising from carbonization processing in terms of their ethnopharmacology, quality control, chemical compositions, biological activities, pharmacological mechanisms, and clinical uses. In this study, a total of 56 chemical constituents were identified and isolated from ZR and CZR, which primarily encompassed volatile oils, gingerols, and diphenylheptane compounds. CZR's pharmacological effects include hemostatic, anti-oxidant, analgesic, antibacterial, anti-cancer, and other biological activities. ZR has pungent and warm properties. It is a Yang-supplementing herbal medicine for ailments exacerbated by cold or damp climatic influences. CZR is a product of ZR after undergoing high temperature, with diminished intensity of its pungent and warm attributes. This change leads to a more gradual treatment efficacy, renowned hemostatic effects and its ability to gently invigorate the spleen and effectively alleviate diarrhea. Currently, research on the pharmacological mechanism of CZR is mainly focused on the effects of CZR on coagulation and fibrinolysis. Although the healing effect of CZR has long been known, and some correlation has been found between the changing composition and the changing color of the decoctions, people still lack relatively clear processing mechanisms to reflect the characteristics and specific quality standards of the ingredients of CZR's hemostatic effect. This review provides a systematic summary on quality control, chemical composition, ethnopharmacology, and pharmacology of CZR, offering novel perspectives for advancing the exploration of additional carbonized herbal medicine and fostering their application in clinical settings

Scientific supervision and subject-oriented development of China clinical research / 中国胸心血管外科临床杂志

@#At the end of 2022, the National Medical Products Administration (NMPA), in conjunction with the National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College raised for the first time the important issue of clinical research globally: whether the source of the death time of clinical trials based on the simple follow-up records is credible, and proposed a consensus document on the source of the death time of clinical trials. The results were published in The Lancet Regional Health-Western Pacific, which attracted wide attention and recognition from the international industry. This is the first time that the China consensus on quality standards for clinical research has been ahead of the U.S. Food and Drug Administration and other international colleagues. The NMPA has been leading China in promoting the scientific development of clinical research, so as to constantly establish and improve the scientific regulatory system and ecological system, and promote China's full integration into the global pharmaceutical research and development system. China clinical research institutions and the whole industry are also gradually from standardized development to scientific development, high-quality development process. In this study, we summarized the scientific and subject-oriented development of China clinical research industry in recent years, and continuously strengthened the international competitiveness of China pharmaceutical industry. It is suggested that scientific thinking model should be used to deal with the normative problems in clinical research and promote the development of medical model to scientific model.

Treatment Response Evaluation by Computed Tomography Pulmonary Vasculature Analysis in Patients With Chronic Thromboembolic Pulmonary Hypertension

Objective@#To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. @*Materials and Methods@#A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both noncontrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm 2 (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). @*Results@#The number, area, and density of the subpleural small vessels increased after treatment by 35.7% (P < 0.001), 13.3% (P = 0.028), and 39.3% (P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio (P = 0.042). The BV5/TBV ratio was negatively correlated with PVR (r = -0.26; P = 0.035) and positively correlated with CI (r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP (r = -0.56; P = 0.001), PVR (r = -0.64; P < 0.001), and CI (r = 0.28; P = 0.049).Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I–IV (P = 0.004) and positively associated with 6MWD (P = 0.013). @*Conclusion@#Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.

Somatostatin-Positive Neurons in the Rostral Zona Incerta Modulate Innate Fear-Induced Defensive Response in Mice / 神经科学通报·英文版

Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIrSST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.

Application of project-based learning in clinical teaching of radiation physics for radiotherapy residents / 中华放射肿瘤学杂志

Objective:To observe the effect of project-based learning (PBL) in the clinical teaching of radiation physics.Methods:Thirty-two residents specializing in radiotherapy were included in the study. In the experimental group ( n=16), PBL was adopted, while traditional clinical teaching method was employed in the control group ( n=16). After the rotation, the assessment was conducted, as well as a questionnaire survey was performed, including five aspects: overall satisfaction, understanding of radiation physics knowledge, learning motivation, learning burden, and learning efficiency. Results:The assessment score in the experimental group was 86.31±5.41, which was higher than 75.28±5.91 in the control group, and the difference was statistically significant. Residents in the experimental group were satisfied with the effect of PBL.Conclusion:Compared with the traditional teaching method, PBL can improve the learning motivation, efficiency, and performance of radiotherapy residents, which is highly recognized by the residents.

Progress on clinical drug trials of esophageal squamous cell carcinoma in China from 2012 to 2021 / 中国胸心血管外科临床杂志

@#Objective     To summarize the progress and trend on clinical drug trials of esophageal squamous cell carcinoma in China. Methods     Based on the clinical drug trial registration and information disclosure platform and the drug data query system of the National Medical Products Administration, the characteristics of clinical trials, investigational drugs and listed drugs of esophageal squamous cell carcinoma in China from 2012 to 2021 were analyzed. Results     From 2012 to 2021, a total of 49 clinical drug trials of esophageal squamous cell carcinoma were registered in China, accounting for 1.6% of all clinical trials of anticancer drugs. Among them, there were 39 (79.6%) trials initiated by domestic pharmaceutical enterprises, 6 (12.2%) for adjuvant and neoadjuvant treatment, and 9 (18.4%) for local treatment. There were differences in the treatment line distribution between global and domestic enterprise-initiated trials (P=0.032). The above trials covered 29 investigational drugs, including 23 (79.3%) targeted drugs, most of which targeted programmed death-1, programmed death-ligand 1 and epidermal growth factor receptor. From 2012 to 2021, there were 2 drugs for esophageal squamous cell carcinoma listed in China, both of which were approved for the first-line and second-line treatment. Conclusion     Great achievements have been made in the clinical development of esophageal squamous cell carcinoma drugs in China. It is suggested that domestic enterprises increase the investment of esophageal squamous cell carcinoma, pay attention to adjuvant and local treatment, explore novel targets and drug categories, and focus on the details of pivotal trials.

Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase Ⅱ trial / 中华肿瘤杂志

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021 / 中华肿瘤杂志

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

Long-term outcomes of watch&wait (W&W) after neoadjuvant treatment in patients with rectal cancer / 中华放射肿瘤学杂志

Objective:To compare the outcomes of watch&wait (W&W) strategy in patients with locally advanced rectal cancer who achieved complete clinical response (cCR) after neoadjuvant therapy, with those who obtained pathological complete response (pCR) after total mesorectal excision (TME).Methods:This is a retrospective cohort analysis study. Patients histologically proven with locally advanced rectal adenocarcinoma (stage Ⅱ-Ⅲ) who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing neoadjuvant therapy and follow-up ≥1 year (W&W group), and patients who did not have cCR but pCR after TME (pCR group). The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (NR-DFS), and organ preservation rate. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM).Results:A total of 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (12.1-79.9 months). No difference was observed in the 3-year OS (97.1% vs. 96.7%) and 5-year OS (93.8% vs. 90.9%, P=0.696) between the W&W and pCR groups. Patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs. 43.5%, P<0.001), better 3-year DFS (83.6% vs. 97.0%) and 5-year DFS (83.6% vs. 91.2%, P=0.047) compared with those achieving pCR. The 3-year NR-DFS (95.9% vs. 97.0%) and 5-year NR-DFS (92.8% vs. 97.0%, P=0.407) did not significantly differ between the W&W and pCR groups. Local regeneration occurred in six cases, and 87.7% of patients had successful rectum preservation in the W&W group. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs. 26.5%, P<0.001) was noted in the W&W group. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19.0 vs. 9.8 weeks, P<0.001). Conclusions:The oncological outcomes of W&W strategy in patients with locally advanced rectal cancer are safe and effective, significantly improving the quality of life. Longer interval for cCR evaluation may improve rectal organ preservation rate.

Local recurrence pattern of pT 1-2N 1 breast cancer after modified radical mastectomy—a pooled-analysis of 5442 patients from 12 centers / 中华放射肿瘤学杂志

Objective:To analyze locoregional recurrence (LRR) pattern of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, with and without adjuvant radiotherapy (RT). Methods:A total of 5442 eligible patients with breast cancer from 12 Chinese centers were included. The LRR sites and the effect of RT at different sites on recurrence in patients with and without RT were analyzed. The Kaplan-Meier method was used to calculate the cumulative LRR rate, and the difference was compared by the log-rank test.Results:With a median follow-up time of 63.8 months for the entire cohort, 395 patients developed LRR. The chest wall and supraclavicular fossa were the most common LRR sites, regardless of RT or molecular subtypes. The 5-year chest wall recurrence rates for patients with and without chest wall irradiation were 2.5% and 3.8%( P=0.003); the 5-year supraclavicular lymph nodal recurrence rates for patients with and without supraclavicular fossa irradiation were 1.3% and 4.1%( P<0.001); the 5-year axillary recurrence-free rates for patients with and without axillary irradiation were 0.8% and 1.5%( HR=0.31, 95% CI: 0.04-2.23, P=0.219); and the 5-year internal mammary nodal recurrence-free rates for patients with and without internal mammary nodal irradiation were 0.8% and 1.5%( HR=0.45, 95% CI: 0.11-1.90, P=0.268). Conclusions:The chest wall and supraclavicular fossa are the most common LRR sites of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, which is not affected by adjuvant RT or molecular subtypes. The chest wall and supraclavicular fossa irradiation significantly reduce the risk of recurrence in the corresponding area. However, axillary and internal mammary nodal irradiation has no impact on the risk of recurrence in the corresponding area.

Preliminary application of MR-Linac in breast cancer radiotherapy in a single academic center / 中华放射肿瘤学杂志

Objective:To describe a prospective study of pre-operative tumor-bed boost performed at the 1.5 T MR-Linac in combination with adjuvant whole breast irradiation, and a first case, with an accentuation on clinical feasibility and safety.Methods:A phase II, single arm study recruiting early stage patients follows a paradigm that first boosts the tumor bed and then undergoes breast conservative surgery in 2 weeks, and last irradiates the whole breast in 6 weeks. The primary endpoint is ≥ grade 2 acute breast toxicity. A 43 years old patient affected by a breast carcinoma, not special type of the right-sided lateral quadrant, staged cT 2N 0M 0, was planned and treated. The dose, 8 Gy for one time, was calculated by Monaco on CT simulation images. Both the air electron stream effect (ESE) and the electron return effect (ERE) at the presence of 1.5 T magnetic field were evaluated. During the pre-treatment evaluation, we carried out adaptation-to-position adjustment. Results:The normal organ dosimetry is within toleration. The Dmax to the skin, the chin and the right upper arm was 8.44 Gy, 28.5 cGy and 17.8 cGy, respectively. There was no increased toxicity from ERE and ESE, and the treatment was well tolerated without > grade 1 acute toxicity. The patient received breast conservative surgery on day 7 without delayed wound healing.Conclusions:This is the first case successfully treated within a clinical trial by pre-operative tumor-bed boost under 1.5 T MR-Linac in our institution. More participants are needed to validate and optimize the paradigm.