Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Mechanisms of cholesterol metabolism imbalance in a PA-induced non-alcoholic fatty liver disease cell model / 中国药科大学学报

@#Liver cholesterol metabolism disorder plays an important role in the development of non-alcoholic fatty liver disease (NAFLD).In order to reveal the molecular mechanism of cholesterol homeostasis imbalance induced by saturated fatty acids, HepG2 cells were stimulated with palmitic acid (PA).Lipids accumulation was analyzed by Oil Red O staining, intracellular triglyceride and cholesterol quantification.The level of genes and proteins related to cholesterol homeostasis was measured by RT-qPCR and western blotting.Additionally, intracellular bile acids and mitochondrial oxysterols were detected by LC-MS/MS.The results demonstrated that intracellular lipids such as TG and TC were significantly increased in the model with PA stimulation.Although no significant difference was detected in genes related to cholesterol synthesis and uptake, the protein expression of ABCG5 and LXRα were significantly down-regulated, indicating a decrease in cholesterol efflux.Meanwhile, the gene expression of STARD1 and CYP7B1, which are responsible for bile acid alternative synthesis, were markedly enhanced, along with a significant increase of cholesterol and 27-OHC in mitochondria and CDCA in cells.These results suggested that PA overload may disrupt cholesterol homeostasis by inhibiting cholesterol efflux and promoting bile acids synthesis.

N6-Methyladenosine Methyltransferase METTL3 Alleviates Diabetes-Induced Testicular Damage through Modulating TUG1/Clusterin Axis

Background@#The present study investigated the regulatory effects of N6-methyladenosine (m6A) methyltransferase like-3 (METTL3) in diabetes-induced testicular damage. @*Methods@#In vivo diabetic mice and high glucose (HG) treated GC-1 spg cells were established. The mRNA and protein expressions were determined by real-time quantitative polymerase chain reaction, Western blot, immunofluorescence and immunohistochemistry staining. Levels of testosterone, blood glucose, cell viability, and apoptosis were detected by enzyme-linked immunosorbent assay, MTT, and flow cytometry, respectively. Molecular interactions were verified by RNA immunoprecipitation and RNA pull-down assay. Histopathological staining was performed to evaluate testicular injury. @*Results@#METTL3 and long non-coding RNA taurine up-regulated 1 (lncRNA TUG1) were downregulated in testicular tissues of diabetic mice and HG-treated GC-1 spg cells. METTL3 overexpression could reduce the blood glucose level, oxidative stress and testicular damage but enhance testosterone secretion in diabetic mouse model and HG-stimulated GC-1 spg cells. Mechanically, METTL3-mediated m6A methylation enhanced the stability of TUG1, then stabilizing the clusterin mRNA via recruiting serine and arginine rich splicing factor 1. Moreover, inhibition of TUG1/clusterin signaling markedly reversed the protective impacts of METTL3 overexpression on HG-stimulated GC-1 spg cells. @*Conclusion@#This study demonstrated that METTL3 ameliorated diabetes-induced testicular damage by upregulating the TUG1/clusterin signaling. These data further elucidate the potential regulatory mechanisms of m6A modification on diabetes-induced testicular injury.

Progress in molecular signal pathway of dental fluorosis / 中华地方病学杂志

Dental fluorosis is a manifestation of chronic oral fluorosis caused by excessive fluoride intake in childhood. At present, the molecular mechanism of dental fluorosis is still unclear. Ameloblasts are the most sensitive cells to fluoride in tooth tissue. Fluoride affects the proliferation and secretion of ameloblasts through the role of key molecules in the molecular signal pathways, leading to the formation of dental fluorosis. This paper reviews the relationship between the molecular signal pathways [mitogen-activated protein kinase (MAPK), transforming growth factor-β (TGF-β)/Smad, Wnt, Foxo1/Runx2], stress pathways (endoplasmic reticulum stress and oxidative stress) and the occurrence of dental fluorosis in recent years, in order to deeply understand the pathogenesis of dental fluorosis at the molecular level, and provide new ideas for the prevention and treatment of dental fluorosis.

Establishment of prediction model for severe acute pancreatitis complicated with abdominal hypertension / 中华胰腺病杂志

Objective:To construct the prediction model of SAP complicated with intra-abdominal hypertension (IAH), and evaluate the prediction efficiency of the model.Methods:The clinical data of 322 SAP patients admitted to the emergency department of Cangzhou Hospital of Integrated Chinese and Western Medicine in Hebei Province from January 2017 to December 2021 were retrospectively analyzed. They were divided into IAH group ( n=153) and control group ( n=169) according to whether they had IAH complications or not. The clinical characteristics and laboratory test results of the two groups were compared. Multifactor logistic step-up regression was used to analyze the risk factors of SAP patients complicated with IAH. A nomogram model for predicting SAP complicated with IAH was established by using R software. The receiver operating characteristic curve (ROC) of the model was plotted, and the area under the curve (AUC) was calculated to evaluate its prediction efficiency. Calibration chart, Hosmer-Lemesshow test and decision curve analysis were used to evaluate the prediction accuracy and clinical application value of the model. The Bootstrap method was applied to verify the model internally. Results:In IAH group, cases with body mass index, CRP, procalcitonin (PCT), WBC, acute physiological and chronic health assessmentⅡ (APACHEⅡ) score, modified CT Severity Index score (MCTSI), incidence of complications (abdominal effusion, abdominal infection, gastrointestinal dysfunction, shock, multiple organ dysfunction syndrome), mechanical ventilation, the number of high-volume fluid reactivation (24 h≥4 L) were more than those in control group; serum albumin and serum calcium in IAH group were lower than those in control group, and the differences were statistically significant (all P value <0.05). Multivariate logistic regression analysis showed that serum albumin ( OR=0.815, 95% CI 0.710-0.937), CRP ( OR=1.005, 95% CI 1.002-1.008), MCTSI ( OR=2.043, 95% CI 1.695-2.463), complication of gastrointestinal dysfunction ( OR=4.179, 95% CI 2.170-8.049), and high-volume fluid resuscitation ( OR=4.265, 95% CI 2.269-8.015) were independent risk factors for IAH in SAP.The Nomogram prediction model was established using the five factors above as parameters, and the AUC value for predicting IAH complication was 0.886. The Hosmer-Lemesshow test showed a high consistency between the prediction results and the actual clinical observation results ( P=0.189). The results of decision curve analysis showed that the prediction probability of the model was between 10% and 85%, which could bring more benefits to patients. Conclusions:The early prediction model of SAP with concurrent IAH is successfully established, which can better predict the risk of SAP with concurrent IAH.

Application of a novel modified Blumgart anastomosis in laparoscopic pancreaticoduodenectomy / 中国医师进修杂志

Objective:To investigate the efficacy and safety of a novel modified Blumgart pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy (LPD).Methods:Between May 2021 and January 2022, 13 successive cases from Lihuili Hospital Affiliated to Ningbo University who underwent LPD were enrolled in this retrospective study. The study retrospectively analyzed the demographic characteristics, perioperative outcomes, and pathological results of these cases.Results:Twenty patients underwent LPD success-fully and one required conversion to open surgery. The operative time was (308.6 ± 61.7) min. The duration for PJ was (26.7 ± 4.3) min. The estimated blood loss was (188.1 ± 94.2) ml. The postoperative hospital stay was (14.2 ± 3.5) d. There was one case of biochemical leakage and no case of grade B or grade C pancreatic fistula.Conclusions:The new method is safe, simple and feasible. The novel method could reduce the incidence of pancreatic fistula and other complications after LPD.

Study the change of serum osteosclerotin and Dickkopf-3 expression in elderly patients with intertrochanteric fracture / 中国医师进修杂志

Objective:To investigate the changes of perioperative serum osteosclerosis protein (SOST) and Dickkopf-3 (Dkk-3) in elderly patients with femoral intertrochanteric fracture.Methods:Thirty elderly patients who underwent reduction and fixation of femoral intertrochanteric fracture in Baoding Second Hospital from May 2017 to December 2017 were prospectively selected as the observation group; 30 healthy subjects in the same period were selected as the healthy control group. Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of serum SOST and Dkk-3 at 1 d before operation and at 1, 3, 5 d after operation and compared with the same period of healthy physical examination(normal control group). Spearman rank correlation analysis was used to analyze the correlation between SOST and Dkk-3 and disease activity score (ASDAS) and spinal imaging evaluation score (mSASSS).Results:There was a positive correlation between Dkk-3 level and ASDAS score in the observation group ( r = 0.331, P = 0.012); the level of SOST was negatively correlated with the scores of ASDAS ( r = - 0.162, P = 0.017). The levels of serum SOST and Dkk-3 in the observation group were lower than those in the healthy control group: 1.29(1.00, 2.40) μg/L vs. 1.96(1.63, 2.65) μg/L, (6.11 ± 1.15) μg/L vs. (9.81 ± 1.76) μg/L, P<0.05. The levels of serum SOST and Dkk-3 in the observation group increased first and then decreased on the 1st, 3rd and 5th day after operation. The level of serum Dkk-3 increased to the highest level on the 3rd day after operation, and then decreased gradually, but it was still slightly higher than that before operation. The level of serum SOST in the observation group increased to the highest level 1st day after operation, and decreased at 3rd and 5th day after operation. The perioperative serum levels of SOST and Dkk-3 in the observation group were positively correlated, the correlation coefficient was the largest at 1 day after operation ( r = 0.571) and the lowest before operation ( r = 0.119). Conclusions:The perioperative serum levels of SOST and Dkk-3 in elderly patients with femoral intertrochanteric fracture increased first and then decreased. The change of serum SOST level is more sensitive and can be used as a sensitive index to reflect the change of osteogenic ability.

Effect of Plasmacytoid Dendritic Cell Dose in Grafts on CMV Infection after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation between plasmacytoid dendritic cell (pDC) dose in grafts and the occurrence of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 80 children who received allo-HSCT in Children's Hospital of Soochow University from August 20, 2020 to June 11, 2021 were retrospectively analyzed. Proportions of DC subsets and T-cell subsets in grafts were detected by flow cytometry in order to calculate infused cell dose of each cell. Weekly monitoring of CMV-DNA copies in peripheral blood for each child were performed after transplantation. The last follow-up date was December 31, 2021.@*RESULTS@#All the children gained hematopoietic reconstitution. CMV infection was observed in 51 children (63.8%±5.4%) within the first 100 days after transplantation, including 2 cases developing CMV disease. Univariate analysis indicated that infused doses of DC and pDC were significantly associated with CMV infection within 100 days after allo-HSCT (P <0.05). Multivariate analysis indicated that a high dose infusion of pDC was an independent protective factor for CMV infection within 100 days after allo-HSCT (P <0.05). By the end of follow-up, 7 children died of transplantation-related complications, including 2 deaths from CMV disease, 2 deaths from extensive chronic graft-versus-host disease, and 3 deaths from capillary leak syndrome. The overall survival rate was 91.2%.@*CONCLUSION@#The pDC in grafts may be associated with early infection of CMV after allo-HSCT, while a high infused pDC dose may serve as a protective factor for CMV infection after transplantation.

Analysis of ARX gene variant in a child with X-linked lissencephaly with abnormal genitalia / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic basis for a child with X-linked lissencephaly with abnormal genitalia (XLAG).@*METHODS@#A child with XLAG who had presented at the Third Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to high-throughput sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the result was analyzed by using bioinformatic software.@*RESULTS@#The child was found to have harbored a hemizygous c.945_948del variant in exon 2 of the ARX gene, which as a frameshifting variant has resulted in a truncated protein. His mother was found to be heterozygous for the variant, whilst his father was of wild type. The variant was unreported previously.@*CONCLUSION@#The hemizygous c.945_948del variant of the ARX gene probably underlay the XLAG in this patient. Above finding has provided a basis for the diagnosis and genetic counseling for this family.

Mechanism of Zhenwu Decoction in improving renal inflammatory injury in mice with DN of spleen-kidney Yang deficiency syndrome by regulating ROCK/IKK/NF-κB pathway / 中国中药杂志

To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1β, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease / 神经科学通报·英文版

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Research progress on the prognostic value of the ratio of lymphocytes to C-reactive protein in digestive system neoplasms / 国际肿瘤学杂志

Tumor-associated inflammation is closely related to the development of tumors. The ratio of lymphocytes to C-reactive protein (LCR) is a new marker reflecting the inflammatory state of the body, which plays an important role in predicting the prognosis of digestive system neoplasms. Compared with the detection of lymphocytes or C-reactive protein alone, this marker has higher sensitivity and accuracy, and can provide a new direction for clinical diagnosis and treatment of digestive system neoplasms.

Effects of the optimization and upgrading of auxiliary tools on transaxillary dual-plane breast augmentation / 中华医学美学美容杂志

Objective:To improve the multiple-link operation efficiency, effect and satisfaction of transaxillary dual-plane breast augmentation by optimizing and upgrading the configuration of auxiliary tools.Methods:From January 2019 to May 2021, breast augmentation was performed in 130 female patients (aged 32±8 years) in the Cosmetic and Plastic Center of the First Affiliated Hospital of Harbin Medical University. The study was conducted among 63 patients who were eligible for the criteria of high configuration surgery. 67 patients underwent standard configuration surgery. The average operation time, intraoperative blood loss, drainage volume (24 hours after operation), postoperative visual analog scale (VAS) pain score and satisfaction were statistically analyzed.Results:The data of high configuration method and standard configuration method were compared as follows: average operation time was (78.6±12.2) min / (93.1±12.1) min ( t=15.73, P<0.05); the average intraoperative blood loss was (3.1±1.0) ml / (14.4±3.5) ml ( t=13.83, P<0.05); the drainage volume (24 hours after operation) was (37.2±8.2) ml / (61.4±10.9) ml ( t=20.82, P<0.05); the pain score on the first day after surgery was (6.1±1.7) points / (7.5±1.6) points ( t=8.57, P<0.05). The overall satisfaction rate was 97.1±1.6 / 95.6±2.0 ( t=5.58, P>0.001), at 6 months after operation. No severe complications were found during the follow-up period, such as capsular contracture, hematoma, infection and double bubble deformity. Conclusions:The use of ultrasonic knife with delivery bag is an effective optimization and upgrade of the endoscopic assisted transaxillary dual plane breast augmentation. The advantages of this method are obvious, highly efficient, safe, effective and satisfactory. It is worthy of clinical application and promotion.

Disease-modifying therapy for multiply system atrophy / 中华老年医学杂志

Multiple system atrophy(MSA)is a rare and fatal neurodegenerative disease occurring in middle-aged and older people, mainly characterized by autonomic nervous system and motor dysfunction.At present, there is no effective method to prevent or reverse its progression, and its treatment is mostly symptom-based, with limited success.A large number of interventional trials have been conducted to explore new treatments for MSA, but there is no clearly effective disease-modifying therapy, probably as a result of poor understanding of the pathophysiological and physiological mechanisms underlying MSA, which may be influenced by multiple factors.The purpose of this paper is to review the existing intervention trials for disease modification therapy of MSA and to discuss the outlook for new therapeutic targets.

Statistical analysis of duration of each phase of Unity MR-linac in clinical application / 中华放射肿瘤学杂志

Objective:To analyze the duration of each phase of Unity MR-linac in clinical application, aiming to provide reference for clinical optimization of the process time.Methods:Clinical data of 55 patients treated with Unity MR-linac were retrospectively analyzed. All patients were divided into the adapt to position (ATP) and adapt to shape (ATS) groups according to the planning method. The duration of each phase in the treatment process, the name and the time of each sequence, the number of beams, segments and total monitor units (MUs) were recorded and compared between two groups. In addition, the set-up time was counted according to different treatment sites. The time of each sequence and set-up time were expressed as the median M (Q 1, Q 3), and the number of beams, segments and total MUs of each plan were described as the mean±SD. Results:42 patients underwent ATP with a total of 305 treatment sessions: setup time was 3(2, 5) min, MR scanning time was 5(4, 7) min, registration time was 3(3, 4) min, adaptive planning time was 8(4, 12) min, beam on time was 8(6, 11) min, and the total time was 30(25, 36) min. 13 patients received ATS with a total of 65 treatment sessions: setup time was 2(2, 3) min, MR scanning time was 7(5, 8) min, registration time was 4(3, 5) min, time of delineation of target and organs at risk was 12(9, 16) min, adaptive planning time was 11(10, 14) min, beam on time was 10(9, 11) min and the total time was 55(49, 61) min. The set-up time according to treatment sites was 4(2, 4) min in the head and neck, 2(2, 4) min in the chest, and 3(2, 5) min in the abdomen. The number of fields, segments and total MUs during ATP were 8.1±1.7, 49.9±31.2, 846.75±363.44 in the head and neck, 8.0±2.0, 60.7±13.3, 790.21±279.00 in the chest, and 9.7±2.0, 81.2±22.3, 2007.32±1053.81 in the abdomen, respectively. The number of fields, segments and total MUs during ATS in head and neck of one case were 13, 39, 993.07, and 9.5±1.5, 65.5±6.3, 2763.26±835.41 in the abdomen.Conclusions:MR-guided radiotherapy yields huge potential in clinical application. However, there is still much room for the improvement of shortening the process duration.

Clinical dosimetry commissioning of 1.5 T MR-linac / 中华放射肿瘤学杂志

Objective:To introduce the clinical dosimetry commissioning methods and results of the 1.5 T MR-linac.Methods:In May, 2019, an Elekta Unity 1.5 T MR-linac was installed in Cancer Hospital, Chinese Academy of Medical Sciences and dosimetry commissioning was performed with magnetic field compatible measuring instruments. Commissioning items include absolute dose calibration, data acquisition and planning system model verification.Results:Absolute dose calibration in magnetic field should be corrected by magnetic field correction factor. The standard output dose of Unity was 87 cGy. Gamma analysis (3%/2 mm) was performed on the beam collection data and the planning system calculation data. The average pass rate of dose verification of standard field test cases was 96.41%, and the TG119 test case was 98.24%. The IROC end to end test case was 97.5%(7%/4 mm).Conclusions:The planning system model and the beam collection data have good consistency. The dose verification results of the standard field and TG119 test cases meet the general tolerance limit requirements of the AAPM TG218 report, and the verification results of the IROC end-to-end test cases meet the IROC center standards.

The standard adapt-to-shape workflow for prostate cancer on MR-linac—Experience from National Cancer Institute/Cancer Hospital, Chinese Academy of Medical Sciences / 中华放射肿瘤学杂志

With aligned MR registration, the MR-Linac provides superior soft tissue resolution for prostate cancer. No fiducial markers or electromagnetic transponders insertion is needed to guarantee high-precision radiotherapy. The highly-recommended Adapt-To-Shape (ATS) workflow can resolve all the problems encountered during prostate cancer radiotherapy, including prostate volume changes and adjacent organs motion, both inter-fractionally and intra-fractionally. With all the above advantages, MR-Linac performs outstandingly than conventional linac in prostate cancer RT delivery, and probably helps us to reduce the CTV-PTV margin safely in the near future. Nevertheless, it is difficult to implement the ATS workflow in clinical practice. In this article, the standard ATS workflow for prostate cancer was summarized based on our own experience.

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.

Preliminary study of clinical application of magnetic resonance linear accelerator in liver malignancies / 中华放射肿瘤学杂志

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.

Research progress on the effects of various macro and trace elements on fluorosis / 中华地方病学杂志

Endemic fluorosis is a common biogeochemical disease. Although the etiology is clear, its molecular mechanism is not fully understood. So far, there is no specific method to effectively treat fluorosis, mainly to prevent. In recent years, a large number of studies have confirmed that a variety of macro elements such as calcium, magnesium, phosphorus, and trace elements such as selenium and boron play a positive regulatory role in the occurrence and development of fluorosis, and have different degrees of influence in the body's antagonism against fluorosis. High levels of trace elements such as arsenic, lead, aluminum and chromium are risk factors for fluorosis. In view of the importance of a variety of macro and trace elements in human nutrition and health, this article reviews the latest developments in multiple elements and fluorosis, especially skeletal fluorosis and dental fluorosis, in order to further understand the causes of fluoride-induced health damage, and provide theoretical reference for improving the prevention strategies of fluorosis in a targeted manner.