Definitive treatment of lung cancer with radiotherapy is challenging, as respiratory motion and anatomical changes can increase the risk of severe off-target effects during radiotherapy. Online adaptive radiotherapy (ART) is an evolving approach that enables timely modification of a treatment plan during the interfraction of radiotherapy, in response to physiologic or anatomic variations, aiming to improve the dose distribution for precise targeting and delivery in lung cancer patients. The effectiveness of online ART depends on the seamless integration of multiple components: sufficient quality of linear accelerator-integrated imaging guidance, deformable image registration, automatic recontouring, and efficient quality assurance and workflow. This review summarizes the present status of online ART for lung cancer, including key technologies, as well as the challenges and areas of active research in this field.
Humans ; Lung Neoplasms/radiotherapy* ; Radiotherapy Planning, Computer-Assisted/methods*

OBJECTIVE To study the repair effect of ephedrine on lipopolysaccharide （LPS）-induced microglia function injury and its mechanism. METHODS Human microglia cells （HMC3） were used as research objects to investigate the effects of different concentrations of ephedrine （75， 150， 300， 600 μg/mL） on the viability and apoptosis of HMC3 cells. HMC3 cells were divided into control group （without drug intervention）， LPS group （1 μg/mL）， ephedrine group （1 μg/mL LPS+300 μg/mL ephedrine）， BAY11-7082 group [1 μg/mL LPS+5 μmol/L nuclear factor-κB （NF-κB） pathway inhibitor BAY11-7082]， inhibitor group （1 μg/mL LPS+300 μg/mL ephedrine+5 μmol/L BAY11-7082） and activator group （1 μg/mL LPS+300 μg/mL ephedrine+1 μmol/L NF-κB pathway activator Prostratin）. After 24 hours of drug treatment， cell migration， the levels of soluble interleukin-6（sIL-6）， interleukin-10（IL-10）， superoxide dismutase（SOD）and malondialdehyde（MDA）， and the expressions of NF-κB pathway-related proteins were all detected. RESULTS The viability of HMC3 cells could be increased significantly by 300 μg/mL ephedrine， while the apoptotic rate was decreased significantly （P＜0.05）. Compared with the control group， the number of migrating cells was increased significantly in the LPS group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were increased significantly， while the levels of IL-10 and SOD were decreased significantly （P＜0.05）. Compared with the LPS group， the above indexes were reversed significantly in the ephedrine group and BAY11-7082 group （P＜0.05）. Compared with the ephedrine group， the number of migrating cells was decreased significantly in the inhibitor group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were decreased significantly， while the levels of IL-10 and SOD were increased significantly （P＜0.05）. The above indexes were reversed significantly in the activator group （P＜0.05）can repair cell injury by inhibiting LPS induced apoptosis， migration， inflammation and oxidant stress of HMC3 cells， the mechanism of which may be associated with inhibiting the activity of the NF-κB signaling pathway.

Objective:To introduce a surgical technique of " short distances and multi-segment" buried-guiding suture method and its effects in the surgery of early descent of prosthesis after augmentation mammaplasty.Methods:From August 2019 to January 2022, 15 cases of early descent of prosthesis after augmentation mammaplasty due to axillary approach breast augmentation for micromastia were admitted to the Plastic Surgery Department of Sichuan Provincial People′s Hospital, aged 23-35 years (27.3±3.6) and duration of dislocation from 16 to 35 days (23.8±5.8). There were 12 patients showed unilateral prosthesis drops and 3 patients showed bilateral prosthesis drops. " Short distances and multi-segment" buried-guiding suture method was used to solve the problem, i. e., 2-0 non-absorbable sutures were used to eliminate the lower pole of prosthetic cavity with " short distances and multi-segment" sutures. The distance from the nipple to the midline of the sternum, the distance from the sternotomy to the nipple, the distance from the nipple to the inframammary fold and the distance from the midclavicular point to the inframammary fold were measured bilaterally before and after surgery, and statistical analysis was performed to evaluate the efficacy of the " short distances and multi-segment" buried-guiding suture method for early descent of prosthesis after breast augmentation.Results:All incisions healed by first intention without complications such as hematoma, infection, or scar hyperplasia. 15 patients were followed up for 6-12 months (8.0±1.9). 14 patients were satisfied with the results after surgery, and 1 patient received satisfactory results after secondary surgery. The distance from nipple to inframammary fold was shortened by 0.8-1.4 cm after surgery (1.2±0.2), and the distance from mid-clavicle to inframammary fold was shortened by 1.0-1.6 cm (1.3±0.4), and the differences were statistically significant as compared with the values before surgery ( t=31.17, P<0.05; t=33.78, P<0.05). After surgery, the change in the distance from nipple to sternal was 0.1-0.3 cm (0.16±0.10), and the change in the distance from sternal notch to nipple was 0-0.2 cm (0.12±0.10), and the differences were not statistically significant ( P>0.05). Conclusions:With the advantages of simple operation, little trauma and no additional incision, the " short distance and multi-stage" buried-guiding suture method in the surgery of early descent of prosthesis after augmentation mammaplasty is worthy of clinical application.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To investigate the risk factors for lymph node metastasis in patients with early gastric cancer and establish a model for prediction of risk.Methods:The cohort of this retrospective observational study comprised 1096 patients who had undergone radical gastric cancer surgery combined with standard D1 lymphadenectomy and been diagnosed with early gastric cancer by postoperative pathology in Zhongshan Hospital affiliated with Fudan University from January 2016 to July 2022. The patients were allocated to groups with and without lymph node metastases. Clinicopathological characteristics were compared between the two groups and multi-factor logistic regression analysis used to identify independent risk factors for lymph node metastasis in patients with early gastric cancer. Indications for endoscopic resection in the Japanese Gastric Cancer Association (JGCA) guideline were also incorporated into construction of the model. The patient cohort was divided into training and validation sets in a 6:4 ratio. The identified independent risk factors were used to construct a predictive nomogram. Receiver operating characteristic curves were plotted separately and the difference between them in predictive efficacy was compared using the area under the curve (AUC).Results:A total of 1,096 patients with early gastric cancer were included, with 750 males and 346 females. Their average age was (61.4±10.9) years old, and the mean tumor diameter was (23.8±11.4) mm. Among them, 188 patients (17.2%) had positive lymph node metastasis, with 109 cases in N1 stage, 42 cases in N2 stage, and 37 cases in N3 stage. Additionally, 462 patients were in T1a stage, while 634 patients were in T1b stage. Univariate analysis showed that tumor diameter, location, Lauren classification, gross morphology, histological type, intravascular invasion, ulceration, differentiation type and tumor T stage were associated with lymph node metastasis after radical gastrectomy for early gastric cancer (all P<0.05). Multifactorial analysis showed that the presence of intravascular invasion (OR=14.822, 95%CI: 9.323–23.572, P<0.001), undifferentiated type (OR=3.095, 95%CI: 1.649–5.811, P<0.001), tumor T1b (OR=1.798, 95%CI: 1.053–3.079, P=0.032), and tumor diameter ≥2 cm (OR=1.229, 95%CI: 1.031–1.469, P=0.022) were independent risk factors for lymph node metastasis. The baseline data of the training set and validation set were consistent in terms of balance (all P>0.05). We used the above variables to establish a predictive nomogram for lymph node metastasis in patients with early gastric cancer. The AUC values obtained from the validation of the model in the training and validation sets were 0.880 (95%CI: 0.849–0.911) and 0.881 (95%CI: 0.841–0.921), respectively, and were significantly better than the predictive efficacy based on the JGCA guideline (AUC=0.777, 95%CI: 0.746–0.809, P<0.001). Conclusions:Patients with early gastric cancer and intravascular invasion, undifferentiated tumors, tumor T1b, and diameter ≥2 cm are at higher risk of postoperative lymph node metastasis than other patients. The predictive model developed in this study more accurately predicts lymph node metastasis in patients with early gastric cancer than previously proposed methods.

Objective:To investigate the risk factors for lymph node metastasis in patients with early gastric cancer and establish a model for prediction of risk.Methods:The cohort of this retrospective observational study comprised 1096 patients who had undergone radical gastric cancer surgery combined with standard D1 lymphadenectomy and been diagnosed with early gastric cancer by postoperative pathology in Zhongshan Hospital affiliated with Fudan University from January 2016 to July 2022. The patients were allocated to groups with and without lymph node metastases. Clinicopathological characteristics were compared between the two groups and multi-factor logistic regression analysis used to identify independent risk factors for lymph node metastasis in patients with early gastric cancer. Indications for endoscopic resection in the Japanese Gastric Cancer Association (JGCA) guideline were also incorporated into construction of the model. The patient cohort was divided into training and validation sets in a 6:4 ratio. The identified independent risk factors were used to construct a predictive nomogram. Receiver operating characteristic curves were plotted separately and the difference between them in predictive efficacy was compared using the area under the curve (AUC).Results:A total of 1,096 patients with early gastric cancer were included, with 750 males and 346 females. Their average age was (61.4±10.9) years old, and the mean tumor diameter was (23.8±11.4) mm. Among them, 188 patients (17.2%) had positive lymph node metastasis, with 109 cases in N1 stage, 42 cases in N2 stage, and 37 cases in N3 stage. Additionally, 462 patients were in T1a stage, while 634 patients were in T1b stage. Univariate analysis showed that tumor diameter, location, Lauren classification, gross morphology, histological type, intravascular invasion, ulceration, differentiation type and tumor T stage were associated with lymph node metastasis after radical gastrectomy for early gastric cancer (all P<0.05). Multifactorial analysis showed that the presence of intravascular invasion (OR=14.822, 95%CI: 9.323–23.572, P<0.001), undifferentiated type (OR=3.095, 95%CI: 1.649–5.811, P<0.001), tumor T1b (OR=1.798, 95%CI: 1.053–3.079, P=0.032), and tumor diameter ≥2 cm (OR=1.229, 95%CI: 1.031–1.469, P=0.022) were independent risk factors for lymph node metastasis. The baseline data of the training set and validation set were consistent in terms of balance (all P>0.05). We used the above variables to establish a predictive nomogram for lymph node metastasis in patients with early gastric cancer. The AUC values obtained from the validation of the model in the training and validation sets were 0.880 (95%CI: 0.849–0.911) and 0.881 (95%CI: 0.841–0.921), respectively, and were significantly better than the predictive efficacy based on the JGCA guideline (AUC=0.777, 95%CI: 0.746–0.809, P<0.001). Conclusions:Patients with early gastric cancer and intravascular invasion, undifferentiated tumors, tumor T1b, and diameter ≥2 cm are at higher risk of postoperative lymph node metastasis than other patients. The predictive model developed in this study more accurately predicts lymph node metastasis in patients with early gastric cancer than previously proposed methods.

Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies.
Animals ; Brain ; CRISPR-Cas Systems/genetics* ; Dependovirus/genetics* ; Haplorhini ; Phenotype ; Protein Kinases/genetics*

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

Objective:To screen serum protein markers and evaluate their diagnostic application value in hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).Methods:Serum samples of patients with HBV-ACLF, chronic hepatitis B (CHB) and normal healthy volunteers ( n = 5/group) were determined by cytokine antibody chip in line with the Chinese Diagnostic Standards Study for HBV-ACLF (COSSH-ACLF) cohort. The differentially expressed proteins significance were identified by microarray analysis and prediction. The preliminary serological markers of HBV-ACLF were screened for diagnosis. The potential markers were determined by enzyme-linked immunosorbent assay (ELISA), area under the receiver operating characteristic curve (AUROC) analysis and liver tissue immunohistochemistry for the diagnosis of HBV-ACLF. Student t-test or Mann-Whitney U test were used to compare the continuous measurement data between the two groups, and analysis of variance and Kruskal-Wallis test were used to compare the continuous measurement data between multiple groups. Results:Cytokine antibody chip preliminary screening results showed that the expression levels of these six cytokines, namely, macrophage inflammatory protein 3α (MIP-3α), hepatocyte growth factor, E-selectin, osteopontin, growth differentiation factor 15 and carcinoembryonic antigen-related cellular adhesion molecule 1 were significantly increased in the HBV-ACLF group. Among them, the expression level of MIP-3α was significantly higher in the HBV-ACLF group (99.6 times higher than CHB group and 146.9 times higher than healthy volunteers’ group, respectively, P < 0.0001) as validated by serum ELISA in 132 HBV-ACLF cases, 91 CHB cases and 72 healthy volunteers. AUROC analysis showed that the high expression of MIP-3α could be used as a marker to distinguish patients with HBV-ACLF from CHB. The AUROC was 0.995 (95% CI: 0.990 ~ 1.000), with sensitivity and specificity of 95.5% and. 98.9%, respectively. Immunohistochemistry showed that MIP-3α was positively expressed in HBV-ACLF-derived liver tissues, and negatively expressed in CHB-derived liver and normal liver tissues. Conclusion:Serum MIP-3α level is closely related to the pathological characteristics of HBV-ACLF. Therefore, it may be used as a potential serological marker for the diagnosis of HBV-ACLF.

Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.