Objective To investigate the effect of field angle on the results of in vivo dose validation of electronic portal imaging device(EPID)in patients.Methods Design the mold test and analyze the influence of different mold thicknesses and different frame angles on the 2D γ pass rate.Twenty-three patients who un-derwent radiotherapy in the Department of Radiotherapy of Jinhua Municipal Central Hospital from January to June 2023 were selected as the research object.In vivo dose verification was carried out during treatment to obtain 2D γ pass rate using same-day sector beam CT(FBCT)of planned CT and executive image guided(IG-RT)as reference images,and the influence of field angle on pass rate was analyzed.Results When the frame angle was unchanged,the area of the shooting field was larger than 17 cm×17 cm,and the 2D γ passing rate decreased with the increase of the thickness.The frame angle had no effect on the 2D γ pass rate when the mold thickness was constant.In clinical treatment data,the passage rate of 2D γ near 0°/180° was higher than that near 90°/270°(P＜0.05),and the passage rate near 90°/270° in the FBCT group was higher than that in the IGRT group(P＜0.05).The median passing rate of 3 mm 2D γ was 97.97％in 3％of the 23 patients.The non-IGRT group was 96.81％,the IGRT group was 97.89％,the FBCT group was 98.94％.There was a statistically significant difference in 2D γ passing rate between the non-IGRT group and the IGRT group(Z=-5.083,P＜0.05),and there was a statistically significant difference in 2D γ passing rate between the IGRT group and the FBCT group(Z=-10.657,P＜0.05).Conclusion Clinically,the difference of pass rate in vi-vo dose verification at different rack angles is mainly due to the difference of images within and between ses-sions.Using same-day FBCT as the reference image for in-vivo dose verification can improve the accuracy of pass rate and eliminate the influence of image difference between sessions.

Objective To determine the median effective dose(ED50)of remimazolam for preoperative sedation in pediatric patients aged 1-6 years using the modified Dixon sequential method.Methods This is a prospective clinical study.Pediatric patients scheduled for elective short surgery(surgery time≤1 h)under general anesthesia from January to July 2023 were selected.Inclusion criteria were age 1-6 years,an ASA physical status Ⅰ-Ⅱ and the preoperative parent separation anxiety scale(PSAS)score≥3 points.Remimazolam was administered intravenously preoperatively,and its sedative effect was assessed.The modified Dixon sequential method was used to determine the ED50 of remimazolam,with the initial dose set at 0.10 mg/kg and the dose increment set at 0.02 mg/kg.Sedation was considered successful(positive,included in positive group)if the child with sedation score≥2 points,preoperative PSAS score<3 points,and the mask acceptance score of 4 points during anesthesia induction.If any criterion was not met,sedation was considered failure(negative,included in negative group),and the next patient's dosage was increased by 0.02 mg/kg based on the previous patient's dosage.The test was completed after 7 consecutive positive and negative turning points appeared alternately.Probabilistic unit regression analysis was used to determine the ED50,ED95 and the corresponding 95%confidence interval(CI)of remimazolam for preoperative sedation.Postoperative recovery time and adverse events such as airway spasm,respiratory depression,hypotension,nausea and vomiting during anesthesia were recorded.Results A total of 23 pediatric patients were included,with 13 in positive group and 10 in negative group.There were no statistically significant differences in mean arterial pressure,pulse oxygen saturation or heart rate before and after sedation(P>0.05).Compared with negative group,positive group showed a significant reduction in preoperative parent separation anxiety and an increase in mask acceptance during anesthesia(P<0.05).There was no significant difference in sedation score and anesthesia awakening time between two groups(P>0.05).The ED50 of remimazolam for preoperative sedation in pediatric patients aged 1-6 years was 0.051 mg/kg(95%CI 0.033-0.065 mg/kg),and the ED95 was 0.077 mg/kg(95%CI 0.064-0.161 mg/kg).No adverse events such as airway spasm,respiratory depression,hypotension,nausea and vomiting occurred during anesthesia in any of pediatric patients.Conclusion The ED50 of intravenous administration of remimazolam for preoperative sedation in pediatric patients aged 1-6 years is 0.051 mg/kg(95%CI 0.033-0.065 mg/kg).

Objective To observe the clinical efficacy of withdrawal therapy based on regulating nutritive qi and defensive qi(shortened to Tiaohe Yingwei method)in treating sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.Methods Ninety patients with sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type were randomly divided into the treatment group and the control group,with 45 patients in each group.The control group was given oral use of Estazolam by 25%of weekly dose-reduction,while the treatment group was treated with Chinese medicinal decoction of Tiaohe Yingwei Zhumian Prescription based on Tiaohe Yingwei method together with Estazolam.The treatment course for the two groups lasted for 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)scores,total TCM syndrome scores,and Drug-withdrawal Syndrome Scale(DWSS)scores in the two groups were observed before and after treatment.After treatment,the efficacy for improving sleep efficiency value(IUSEV)and clinical safety in the two groups were evaluated.Results(1)During the trial,2 cases fell off in the treatment group,and 43 cases included in the statistics;3 cases fell off in the control group,and 42 cases included in the statistics.(2)After 4 weeks of treatment,the total effective rate for improving IUSEV of the treatment group was 88.37%(38/43),and that of the control group was 61.90%(26/42).The intergroup comparison by non-parametric rank-sum test showed that the efficacy for improving IUSEV in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,obvious reduction was shown in the overall PSQI scores and the scores of the items of sleep quality,time for falling asleep,sleep time,sleep efficiency,sleep disorder and daytime dysfunction in the two groups when compared with those before treatment(P＜0.05).The intergroup comparison showed that except for the items of sleep disorder and daytime dysfunction,the treatment group had stronger effect on decreasing the scores of the remaining items and the overall PSQI scores than the control group(P＜0.05).(4)After treatment,the total scores of TCM syndromes of both groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of the total scores of TCM syndrome in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the total DWSS scores of the two groups were significantly decreased compared with those before treatment(P＜0.05),and the effect on lowering the scores in the treatment group was significantly superior to that in the control group(P＜0.05).(6)During the course of treatment,no significant adverse reactions occurred in the two groups,or no abnormal changes were found in the safety indexes such as routine test of blood,urine and stool,liver and kidney function,and electrocardiogram of the patients.Conclusion Withdrawal therapy based on Tiaohe Yingwei method exerts certain effect for the treatment of sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.The therapy is effective on improving the quality of sleep and reducing the incidence of drug-withdrawal syndrome,and has a high safety.

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.

Objective To investigate the infiltration of peripheral monocyte in the hippocampal CA3 area in neuralgia mice at different time points and explore the effects of the infiltration on neuralgia and the neuralgia-induced anxiety-like behavior in mice.Methods The healthy male C57 mice were randomly divided into four groups:sham,sciatic nerve branch selective injury(SNI)model(SNI),CCR2 inhibitor RS102895(SNI+RS102895)and microglial inhibitor minocycline(MC)(SNI+MC)groups.Both the sham and SNI groups were further divided into 7 days,14 days and 18 days groups,and the SNI+RS102895 and SNI+MC groups were sampled on the 18th day.Neuralgia was induced by SNI,and mechanical hyperalgesia was assessed by paw withdrawal threshold(PWTs)at different time points.Elevated plus maze(EPM)and open field test(OFT)were performed respectively two days and one day before sacrifice.Immunofluorescence was used to observe the expressions of leukocyte differentiation antigen 45(CD45)and the co-expression with microglial markers ionized calcium binding adaptor molecule-1(IBA-1),transmembrane protein 119(TMEM119),astrocyte marker glial fibrillary acidic protein(GFAP),and neuronal marker neuronal nuclei(NeuN)in the hippocampal CA3.The percentage of monocytes in the whole brain of 14 days SNI mice was determined by flow cytometry.Minocycline at 90 mg/(kg·d),RS 102895 at 5 mg/(kg·d)and saline were administered orally on the 5th to 16th day in the corresponding 18 days groups,and the effects of blocking monocyte infiltration on neuralgia and anxiety-like behavior and the expressions of CD45 and 1BA-1 in CA3 region of hippocampus were observed.Results On the first day after SNI,the PWTs of mice in the 7 days and 14 days groups decreased and continued until before sacrifice(P＜0.01).The CD45 expression did little in the 7 days sham group.Compared with the sham group at the same time point,the CD45 expression did not increase in 7 days SNI mice((P＞0.05)and increased significantly in 14 days SNI mice(P＜0.01),only slightly co-expressed with IBA-1 and TMEM119 and no co-expression with GFAP and NeuN,the percentage of monocytes in the whole brain increased significantly in 14 days SNI mice(P＜0.01).Inhibition of microglial activation or CCR2 expression reduced the expression of CD45 in the CA3 in SNI mice(P＜0.01),increased the PWTs(P＜0.01)and alleviated anxiety-like behavior in SNI mice(P＜0.01).Conclusion There was an infiltration of peripheral monocytes in the hippocampal CA3 region after 14 days of SNI-induced neuralgia,which might be involved in the maintenance of neuralgia and the development of neuralgia-induced anxiety-like behaviors.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Objective:To investigate the factors affecting the accuracy of electronic portal imaging device (EPID)-based in vivo dose verification in radiotherapy for patients with lung and esophageal cancers, and to recommend the workflow and specifications for the application of the in vivo dose verification. Methods:This study randomly selected 32 patients who received radiotherapy for esophageal and lung cancers at the Department of Radiation Oncology, Jinhua Municipal Central Hospital from May to August 2022, including 14 lung cancer cases and 18 esophageal cancer cases. Using a uRT-linac 506c linear accelerator, these patients were treated according to the dynamic intensity-modulated radiotherapy (dIMRT) and EPID-based In vivo dose verification ( In vivo EPID) plans developed with the uRT-TPOIS planning system. The In vivo dose verification performed during the treatment included 238 fractions of In vivo EPID and 80 fractions of image-guided radiotherapy (IGRT) for the lung cancer cases, as well as 414 fractions of In vivo EPID and 105 fractions of IGRT for the esophageal cancer cases. The 2D γ passing rate for each irradiation field was obtained according to the set threshold value. Furthermore, fractioned irradiation fields with γ-passing rates below the threshold value were analyzed, and primary factors decreasing the γ-passing rate were further analyzed by combining the online CT images and 3D reconstruction-derived dose. Results:For lung and esophageal cancers, the mean γ-passing rates were 95.1% ± 5.7% and 96.5% ± 4.5%, respectively at 3 mm/5%; 91.5% ± 8.4% and 92.2% ± 4.9%, respectively at 3 mm/3%, and 79.1% ± 14.7% and 83.7% ± 8.2%, respectively at 2 mm/2%, indicating no statistically significant differences between two cancers ( P > 0.05). The average γ passing rate for beam orientations near 0°/180° (Group A) was higher than those near 90°/270° (Group B) 3 mm/5%: Z = -25.4, P < 0.05; 3 mm/3%: Z = -26.8, P < 0.05). The IGRT correction of setup errors significantly improved the γ passing rates (96.3% ± 5.1% and 96.4% ± 4.9%, respectively at 3 mm/5%, Z = -5.50, P < 0.05; 92.3% ± 8.0% and 91.3% ± 7.7%, respectively at 3 mm/3%, Z = -9.54, P < 0.05). The results of In vivo dose verification were affected by changes in the volumes and motion of tumors and normal tissues, radiotherapy positioning, and adequacy of pre-treatment preparation. Conclusions:EPID-based In vivo dose verification during radiotherapy can avoid incorrect irradiation. However, it is necessary to standardize the workflow of the EPID-based In vivo dose verification to avoid the decrease in the γ passing rate caused by artificial factors.

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.
Child ; Female ; Male ; Humans ; Retrospective Studies ; Cytokine Release Syndrome ; COVID-19/complications* ; SARS-CoV-2 ; Brain Diseases/etiology* ; Prognosis ; Seizures ; Cytokines

Objective    To summarize the experience of robot-assisted lung basal segmentectomy, and analyze the clinical application value of intersegmental tunneling and pulmonary ligament approach for S9 and/or S10 segmentectomy. Methods    The clinical data of 78 patients who underwent robotic lung basal segmentectomy in our hospital between January 2020 to May 2022 were retrospectively reviewed. There were 32 males and 46 females with a median age of 50 (33-72) years. The patients who underwent S9 and/or S10 segmentectomy were divided into a single-direction group (pulmonary ligament approach, n=19) and a bi-direction group (intersegmental tunneling, n=19) according to different approaches, and the perioperative outcomes between the two groups were compared. Results    All patients successfully completed the operation, without conversion to thoracotomy and lobectomy, serious complications, or perioperative death. The median operation time was 100 (40-185) min, the blood loss was 50 (10-210) mL, and the median number of dissected lymph nodes was 3 (1-14). There were 4 (5.1%) patients with postoperative air leakage, and 4 (5.1%) patients with hydropneumothorax. No patient showed localized atelectasis or lung congestion at 6 months after the operation. Further analysis showed that there was no significant difference in the operation time, blood loss, thoracic drainage time, complications or postoperative hospital stay between the single-direction and bi-direction groups (P>0.05). However, the number of dissected lymph nodes of the bi-direction group was more than that of the single-direction group [6 (1-13) vs. 5 (1-9), P=0.040]. Conclusion    The robotic lung basal segmentectomy for pulmonary nodules is safe and effective. The  perioperative results of robotic S9 and/or S10 complex segmentectomy using intersegmental tunneling and pulmonary ligament approach are similar.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.