Effect of Stemona tuberosa Alkaloids on Apoptosis and PI3K/Akt and JNK/MAPK Signaling Pathways of Human Lung Cancer A549 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Stemona tuberosa alkaloids （STA） on apoptosis and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and c-Jun N-terminal kinase/p38 mitogen-activated protein kinase （JNK/p38 MAPK） signaling pathways in human lung cancer A549 cells. MethodA549 cells were classified into blank group and STA groups （100， 150， 200， 250， 300 mg⋅L-1）. Thiazole blue （MTT） assay and colony formation assay were used to evaluate the proliferation of A549 cells. Apoptosis was observed based on Hoechst 33258 staining， flow cytometry， and Annexin V-FITC/PI staining. Western blot was employed to detect the expression of apoptosis-related proteins cysteine-aspartic acid protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， and Bcl-2， and the expression of PI3K， phosphorylated （p）-PI3K， Akt， p-Akt， JNK， p-JNK， p38 MAPK， and p-p38 MAPK. ResultCompared with the blank group， STA groups （150， 200， 250， 300 mg⋅L-1） demonstrated the increase in inhibition rate of cell proliferation （P<0.01） and cell clone inhibition rate， and decrease in cell clone formation rate （P<0.01）. In comparison with the blank group， STA groups showed typical characteristics of apoptosis， such as chromatin condensation and enhanced fluorescence reaction. The apoptosis rate of STA groups was significantly higher than that of the blank group （P<0.01）. Compared with the blank group， STA （150， 200， 250， 300 mg⋅L-1） significantly up-regulated the protein expression of Caspase-3 and Bax （P<0.05， P<0.01） and down-regulated the expression of Bcl-2 protein （P<0.01）. Compared with the blank group， STA had no significant influence on the total protein expression of PI3K， Akt， JNK， and p38 MAPK. However， STA （150， 200， 250， 300 mg⋅L-1） significantly decreased the levels of p-PI3K and p-Akt （P<0.05， P<0.01） and increased the level of p-p38 MAPK （P<0.05， P<0.01）. Compared with the blank group， STA （200， 250， 300 mg⋅L-1） significantly raised the level of p-JNK （P<0.05， P<0.01）. ConclusionSTA can inhibit the proliferation and induce the apoptosis of A549 cells by inhibiting PI3K/Akt signaling pathway and activating JNK/p38 MAPK signaling pathway.

Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors / 药物分析学报

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.

Investigation on biological subtypes of depression based on diffusion tensor imaging / 四川精神卫生

BackgroundBeing complex and highly heterogeneous with regard to the etiology and clinical manifestations of depression， neuroimaging studies make a breakthrough for exploring the biological subtypes of depression， while the current data-driven approach for the identification of subtyping depression using structural magnetic resonance imaging （MRI） data is insufficient. ObjectiveTo explore the biological subtypes of depression using diffusion tensor imaging （DTI） and machine learning methods. MethodsA total of 127 patients with depression who attended Beijing Anding Hospital from September 2017 to August 2021 and met the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） diagnostic criteria were included， and another 80 healthy individuals matched for gender and age were recruited through advertisements in surrounding communities during the same period. DTI findings， demographic characteristics and clinical data were collected from all participants. Tract-based spatial statistics （TBSS） and the Johns Hopkins University （JHU） white matter probability maps were used to extract fractional anisotropy （FA） values of white matter tracts. A semi-supervised machine learning technique was used to identify the subtypes， and the FA values for whole brain white matter of patients and controls were compared. ResultsPatients with depression were classified into two biological subtypes. FA values in multiple tracts including corpus callosum and corona radiata of subtype I patients were smaller than those of healthy controls （P<0.01， FDR corrected）， and FA values in middle cerebellar peduncle， left superior cerebellar peduncle and left cerebral peduncle of subtype II patients were larger than those of healthy controls （P<0.01， FDR-corrected）. Baseline Hamilton Depression Scale-17 item （HAMD-17） score yielded no statistical difference between subtype I and subtype II patients （P>0.05）， while subtype I patients scored lower on HAMD-17 than subtype II patients after 12 weeks of treatment （t=2.410， P<0.05）. ConclusionDepression patients exhibit two biological subtypes with distinct patterns of white matter damage. Furthermore， the subtypes respond differently to the medication treatment. ［Funded by the National Key Research and Development Program of China （number， 2016YFC1307200）， the Scientific Research and Cultivation Program of Beijing Municipal Hospitals （number，PX2023066）， Beijing Anding Hospital， Capital Medical University （number，YJ201904， YJ201911）； www.chictr.org.cn number： ChiCTR-OOC-17012566］

Differential diagnosis and surgical management in chondrosarcoma of the jugular foramen / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.

Anti-inflammatory effect and mechanism of the ethanol extract and the drug-containing serum of Zhuang medicine Stahlianthus involucratus on LPS-induced RAW264.7 cell inflammation / 中国药房

OBJECTIVE To study the anti-inflammatory effect and mechanism of the ethanol extract and the drug-containing serum of Zhuang medicine Stahlianthus involucratus on lipopolysaccharide （LPS）-induced RAW264.7 cell inflammation. METHODS The drug-containing serum or blank serum was obtained by intragastrical administration of ethanol extract of S. involucratus （75.35 g/kg） or purified water. Using RAW264.7 cells as objects， RAW264.7 cells were divided into normal control group， LPS group （1 μg/mL）， S. involucratus ethanol extract high-dose， medium-dose and low-dose groups （50， 25， 12.5 μg/mL）， 4% or 15% blank serum groups， 4% or 15% blank serum+LPS groups， 4% or 15% drug-containing serum groups， 4% or 15% drug-containing serum+LPS groups. After culturing for 24 h， cell viability， the contents of nitric oxide tumor necrosis factor α （TNF-α）， interleukinand IL-6 as well as mRNA expressions of Toll-like eceptor 4 （TLR4） and nuclear factor κB （NF- κB） and protein expressions of nitric oxide synthase （NOS） and cyclooxygenase 2 （COX-2） were all detected in each group. 0771-4953513。E-mail：zhuhuagx@163.com RESULTS After culturing for 24 h， there was no statisticalsignificance in the difference of cell viability. Compared with normal control group， the contents of NO， TNF-α， IL-1β and IL-6， mRNA expressions of TLR4 and NF-κB， and protein expressions of NOS and COX-2 were increased significantly in LPS group （P＜0.05）. Compared with 4% or 15% blank serum groups， the levels of above indexes were increased significantly in 4% or 15% blank serum+LPS groups （P＜0.05）. Compared with LPS group， the levels of above indexes were decreased significantly in S. involucratus ethanol extract groups （P＜0.05）. Compared with 4% or 15% blank serum+LPS groups， the levels of above indexes were decreased significantly in 4% or 15% drug-containing serum+LPS groups （P＜0.05）. CONCLUSIONS The ethanol extract and the drug-containing serum of S. involucratus can significantly alleviate LPS-induced inflammatory reaction， the mechanism of which may be associated with inhibiting the activity of TLR4/NF-κB signaling pathway， down-regulating the protein expressions of COX-2 and NOS， and reducing the release of inflammatory factors.

Vascularization of intravitreal injection of Conbercept in the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate retinal vascularization caused by the intravitreal injection of Conbercept in the treatment of a series of retinopathy of prematurity(ROP)cases in Type Ⅰ(threshold and pre-threshold period)and aggressive ROP(A-ROP).METHODS: The data of 34 ROP cases(67 eyes)treated by intravitreal injection of Conbercept(IVC)in the ophthalmology department of the Xiamen Children's Hospital from July 2017 to March 2020 were retrospectively analyzed. Reactivation, which refers to recurrence of acute phase features, occurred at any stage of the disease in the presence or absence of other diseases. RESULT: The average gestational age of the 34 children was 28.82±2.32wk. The average birth weight was 1155.18±398.22g. The lesion zone of 19 cases(37 eyes)was Zone Ⅰ. In 10 cases(20 eyes), the lesion was in Zone Ⅱ, and in 5 cases(10 eyes), the lesion was in the posterior Zone Ⅱ. The total effective rate of disease control in ROP children treated with once IVC was 73.1%(49/67), and the vascularization of Zone Ⅱ was completed. The patients showed variable changes in the vascularization in Zone Ⅲ. For the patients who received one treatment and did not reactivate, the average rate of Type Ⅰ vascularization of ROP was 9.11±2.49wk, and the A-ROP was 13.40±4.04wk. The rate of A-ROP vascularization in Zone Ⅱ was significantly longer compared to Type Ⅰ.CONCLUSION: IVC effectively completes vascularization in Zone Ⅱ.

Long-term evaluation and physical and mental effects of residual tinnitus following treatment of sudden hearing loss / 中华耳鼻咽喉头颈外科杂志

Objective: To clarify the long-term characteristics of tinnitus following treatment of sudden deafness and its long-term physical and mental effects on patients. Methods: A retrospective analysis was performed on 88 patients (46 males and 42 females; Age from 11 to 89 years) with sudden deafness treated in Department of Otoscope Surgery of Peoples's Libration Army General Hospital in Beijing from April 2020 to January 2021, and the occurrence of tinnitus and treatment effect of all patients were analyzed. Follow-up was conducted for patients with residual tinnitus after treatment for more than 1 year by the investigation and filling in the survey information collection form, Tinnitus Evaluation Questionnaire (TEQ) and Tinnitus Handicap Inventory (THI). Descriptive statistics and SPSS 22.0 software were used for statistical data analysis. Results: In this study, 93.2% (82/88) of patients with sudden deafness were accompanied by tinnitus at the onset, and the proportion of long-term tinnitus after treatment was 90.2% (74/82). After 1 year of treatment for sudden deafness, the improvement of tinnitus was significant in low-frequency sudden deafness compared with those of high-frequency, flat and total deafness sudden deafness (χ2 value was 6.801, 4.568 and 4.038, all P<0.05). In patients with residual tinnitus, 9 (12.2%) patients felt minimal loudness or even no loudness, 34 (46.0%) patients felt slight loudness, 28 (37.8%) patients felt tinnitus was relatively loud, and 3 (4.1%) patients felt tinnitus was loud or noisy. Nine (12.2%) patients's sleep was often affected, 41 (55.4%) patients's sleep was sometimes affected, 9 (12.2%) patients's sleep was rarely affected, 15 (20.3%) patients's sleep was almost not affected. Twenty-eight (37.8%) patients basically completely adapted to tinnitus and 46 (62.2%) patients did not completely adapted to residual tinnitus. Eight (10.8%) patients had no impact on life, 39 (52.7%) patients had slight impact, 22 (29.7%) patients had moderate impact, and the other 5 (6.8%) patients had greater impact. According to tinnitus evaluation questionnaire(TEQ), there were 12 cases (16.2%) of grade Ⅰ, 26 cases (35.1%) of grade Ⅱ, 28 cases (37.8%) of grade Ⅲ, 7 cases (9.5%) of grade Ⅳ and 1 case (1.4%) of grade Ⅴ. According to tinnitus handicap inventory(THI), tinnitus disability was classified into grade Ⅰ, 22 cases (29.7%), grade Ⅱ, 14 cases (18.9%), Grade Ⅲ, 27 cases (36.5%) and grade Ⅳ, 11 cases (14.9%). Conclusion: The rate of residual tinnitus following treatment of sudden deafness is high. Some of the patients can completely adapt residual tinnitus after one year, but some of them will be affected when sleep, work and study. Residual tinnitus can lead to tinnitus disability in different degrees.

Study on the correlation between ceramic and chronic obstructive pulmonary disease in Foshan City / 中华劳动卫生职业病杂志

Objective: To study the correlation between ceramic and chronic obstructive pulmonary disease (COPD), and explore its related risk factors. Methods: In January 2021, five representative ceramic enterprises were selected from Chancheng District, Nanhai District, Gaoming District and Sanshui District of Foshan City. The ceramic workers who came to Chancheng Hospital of Foshan First People's Hospital for physical examination from January to October 2021 were selected as the research objects, and 525 people were included. Conduct questionnaire survey and pulmonary function test. Logistic regresion was performed to analyze the influencing facters of COPD among ceramic workers. Results: The subjects were (38.51±1.25) years old, 328 males and 197 females, and the detection rate of COPD was 9.52% (50/525). The incidence of respiratory symptoms such as dyspnea, chronic cough, wheezing and chest tightness, the detection rates of abnormal lung age, abnormal lung function and COPD in males were higher than those in females (P<0.05). The logistic regression analysis showed that male, age, working years, smoking status and family history of COPD were the risk factors for COPD among ceramic workers (P<0.05) . Conclusion: The ceramic workers are the high risk population of COPD. We should do a good job in health education, and do a regular physical examination to find the changes of lung function in time, and prevent the occurrence of COPD as soon as possible.

Research and application of model fruit fly in prevention and treatment of neuropsychiatric disorders by traditional Chinese medicine and natural compounds: a review / 中国中药杂志

As an important model animal, fruit fly is characterized by outstanding genetic characteristics, relatively perfect nervous system, rapid reproduction, and low cost. Thus, it has been applied in the research on neuropsychiatric disorders in recent years, showing great potential in life science. The incidence of neuropsychiatric disorders has been on the rise, and the disorders have high disability rate and low case fatality rate. The global drug demand for such diseases is second only to cardiovascular and cerebrovascular diseases. At the moment, the demand of the drugs for the diseases have been rising, and it is an urgent task to develop related drugs. However, the research and development of the drugs are time-intensive and have a high failure rate. A suitable animal model can help shorten the time for drug screening and development, thereby reducing the cost and failure rate. This study reviews the application of fruit flies in several common neuropsychiatric disorders, which is expected to provide new ideas for the research and application of the model animals in traditional Chinese medicine.

Systemic Lupus Erythematosus Combined with Chorea: Report of One Case and Literature Review / 中国医学科学院学报

Systemic lupus erythematosus combined with chorea is relatively rare in China,and there are no unified diagnostic criteria or specific ancillary tests.Therefore,it is confirmed by exclusionary clinical diagnosis.To improve the understanding of this disease among rheumatologists,we report the clinical data of a patient with systemic lupus erythematosus combined with chorea admitted to the Department of Rheumatology and Immunology in the First Affiliated Hospital of Jinan University in January 2022.Furthermore,we review the relevant literature in the past 10 years and summarize the clinical features of these cases.

Mechanism of Stemona tuberosa Alkaloids in Inhibiting Proliferation and Inducing Apoptosis of Non-small Cell Lung Cancer NCI-H460 Cells / 中国实验方剂学杂志

ObjectiveTo study the effect and underlying mechanism of Stemona tuberosa alkaloids on the proliferation and apoptosis of human non-small cell lung cancer NCI-H460 cells. MethodNon-small cell lung cancer NCI-H460 cells were divided into a blank group and S. tuberosa alkaloids groups （50， 100， 150， 200， and 250 mg·L-1）. The effect of S. tuberosa alkaloids on the proliferation of human NCI-H460 cells was observed by thiazolyl blue tetrazolium bromide （MTT） assay and colony formation assay. Cell apoptosis was observed by Hoechst 33258 staining and flow cytometry. Real-time fluorescence-based polymerase chain reaction （Real-time PCR） was used to detect the effect of S. tuberosa alkaloids on the mRNA expression of cysteinyl aspartate-specific protease 3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and epidermal growth factor receptor （EGFR）. The protein expression levels of Caspase-3， Bax， Bcl-2， protein kinase B （Akt）， phosphorylated （p-）Akt， EGFR， c-Jun N-terminal kinase （JNK）， p-JNK， p38 mitogen-activated protein kinase （p38 MAPK）， and p-p38 MAPK were measured by Western blot. ResultCompared with the blank group， the S. tuberosa alkaloids groups showed increased inhibition rate on cell proliferation （P<0.01）， reduced number of cell clones formed and the rate of cell clonal formation （P<0.05， P<0.01）， and increased karyopyknosis， cytoplasmic aggregation， and cell apoptosis rate （P<0.01）. The S. tuberosa alkaloids groups at 100， 150， 200， and 250 mg·L-1 showed increased Caspase-3 mRNA expression （P<0.05）， decreased EGFR mRNA expression （P<0.05， P<0.01）， up-regulated protein expression of Caspase-3 and p-JNK （P<0.01）， and down-regulated protein expression of EGFR and p-Akt （P<0.05， P<0.01）. Additionally， compared with the blank group， the S. tuberosa alkaloids groups showed increased expression of Bax mRNA （P<0.01）， decreased expression of Bcl-2 mRNA （P<0.01）， up-regulated protein expression of Bax and p-p38 MAPK （P<0.01）， and down-regulated protein expression of Bcl-2 （P<0.01）. ConclusionsS. tuberosa alkaloids can inhibit proliferation and induce apoptosis of human non-small cell lung cancer NCI-H460 cells， and the mechanism may be related to the inhibition of EGFR protein expression and phosphorylation of Akt protein， as well as the activation of the JNK/p38 MAPK signaling pathway.

Comparison of effects of absolute scatter correction and relative scatter correction on image quality in PET reconstruction / 中华核医学与分子影像杂志

Objective:To study the impact of different scattering correction algorithms in the reconstruction of PET/CT images on image artifacts and the precision of quantitative parameters.Methods:The phantom as described in the National Electrical Manufacturers Association (NEMA) NU2 standard was filled with 18F. The background activity was fixed, and the activity of the solution in the spheres was adjusted to obtain several configurations, including the normal ratio group (4.08∶1) and the extreme ratio group (200∶1). The surface contamination group with the same ratio as the extreme ratio group contained a small radioactive source with different doses of 18F (74, 37, 3.7 and 0.37 MBq) placed at the surface of the phantom. PET/CT images of 30 patients (21 males, 9 females, age: (44.5±10.2) years) from Peking University Cancer Hospital & Institute between July 2012 and December 2021 were retrospectively analyzed, including 10 with normal images ( 18F-FDG) and 20 with abnormal images (10 with dislocation during acquisition, 10 with surface contamination). The images were reconstructed with relative and absolute scattering correction. The phantom was evaluated using the target to background ratio (TBR) and the artifact classification. CV as well as the artifact classification were used to compare the clinical image quality. Mann-Whitney U test and χ2 test were used to analyze data. Results:In the normal ratio group and the extreme ratio group, the TBRs of phantom images reconstructed with relative correction were significantly higher than those with absolute correction (normal ratio group: 3.30(1.94, 4.53) vs 2.72(1.56, 3.56); z=-2.20, P=0.028; extreme ratio group: 105.47(45.62, 162.82) vs 101.36(43.96, 155.57); z=-1.99, P=0.046). In the surface contamination group, with the increase of the activity of the small source, the artifact became more obvious, and the artifact classification score of absolute correction was significantly better than that of relative correction (1.5(1.0, 2.0) vs 2.5(2.0, 3.0); z=-2.00, P=0.046). In the 10 normal 18F-FDG PET/CT patients, the CVliver of the relative correction (9.67%(8.00%, 11.00%)) was significantly lower than that of absolute correction (11.00%(9.00%, 12.00%); z=-2.57, P=0.010), indicating the higher image quality of images with relative correction. In abnormal images, the image quality of absolute correction was significantly higher than that of relative correction with fewer and less severe artifacts (dislocation cases: 9/10 vs 4/10; χ2=5.50, P=0.019; surface contamination cases: 9/10 vs 4/10; χ2=5.50, P=0.019). Conclusions:The relative scattering correction is suitable for normal situations in clinical PET acquisition. However, with dislocation or surface contamination, the absolute scattering correction helps to reduce the artifacts and improve the image quality.

Evaluation of the effect of linker on novel targeted PSMA PET probe / 中华核医学与分子影像杂志

Objective:To prepare a novel targeted prostate specific membrane antigen (PSMA) molecular probe Al 18F-PSMA-136, and evaluate the effects of the change in linker on the biological behavior and tumor targeting ability. Methods:Al 18F-PSMA-136 was prepared by replacing the phenyl of Al 18F-PSMA-137 with cyclohexyl in 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA). The inhibition abilities of PSMA of NOTA-PSMA-136 and NOTA-PSMA-137 were determined by N-acetylated-α-linked acidic dipeptidase (NAALADase) method. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio-high-performance liquid chromatography. The PSMA specificity and tumor targeting capability of the probes were investigated in 22Rv1 (PSMA positive-expressing) cells and mouse models. Independent-sample t test was used to analyze the data. Results:The Ki values of NOTA-PSMA-136 and NOTA-PSMA-137 were 3.41 and 0.30 nmol/L, respectively. The labeling yield of Al 18F-PSMA-136 was (30.1±8.4)% and the specific activity was (18.7±5.3) GBq/μmol. The radiochemical purities of the two probes were both greater than 95% and the stabilities in vitro were both good. Both probes showed PSMA-specific in 22Rv1 cells, but the uptake of Al 18F-PSMA-137 was significantly higher than that of Al 18F-PSMA-136 (1 h: (1.67±0.24) vs (1.00±0.01) percentage injected activity per 1×10 5 cells (%IA/1×10 5 cells): t=4.78, P=0.003; 2 h: (2.11±0.06) vs (1.03±0.06) %IA/1×10 5 cells; t=19.90, P<0.001). MicroPET/CT imaging showed that Al 18F-PSMA-136 and Al 18F-PSMA-137 had similar distribution in vivo, mainly concentrated in kidneys, intestine, gallbladder, bladder and tumor. However, the uptake of Al 18F-PSMA-137 in tumor was significantly higher than that of Al 18F-PSMA-136 (1 h: 1.78±0.10 vs 0.54±0.08; t=13.29, P<0.001; 2 h: 1.95±0.01 vs 0.52±0.11; t=18.53, P<0.001). Conclusion:Changes in the NOTA-conjugated linker can significantly affect the PSMA inhibition ability and tumor targeting, and the imaging effect of Al 18F-PSMA-137 with strong lipophilicity is superior.

Differential diagnosis of vasovagal syncope in children / 国际儿科学杂志

Vasovagal syncope(VVS) is a common clinical reflex syncope, which is easy to occur repeatedly.Although there is no direct life risk, it causes varying degrees of physical injury and psychological disorders to children, affects their daily life and study, and also causes anxiety of parents.At present, the diagnosis of VVS mainly depends on the vertical tilt table test.With the development of translational medicine, identifying VVS and other types of syncope by other methods has achieved important clinical value, which will be more convenient for primary hospital to carry out the related work of syncope diagnosis and treatment.This paper will review the related progress in the differential diagnosis of VVS.

Countertraction method for reduction of irreducible subcoracoid dislocation of the shoulder joint with Hill-Sacks lesion / 中国骨伤

OBJECTIVE@#To investigate clinical outcomes of countertraction method in treating irreducible subcoracoid dislocation of shoulder joint combined with Hill-Sacks injury.@*METHODS@#A total of 56 patients with irreducible subcoracoid dislocation of the shoulder joint combined with Hill-Sacks injury admitted from December 2013 to June 2020 were retrospectively analyzed. Under the anesthesia of shoulder joint cavity injection, the reduction was performed by using anti-traction method (experimental group) and traditional Hippocrates method (control group), 28 cases in each group. There were 11 males and 17 females in experimental group, with an average age of (61.95±19.32) years old, 9 cases on the left side, and 19 cases on the right side. Twelve males and 16 females in control group, with an average age of (63.13±12.75) years old, 11 cases on the left side, 17 cases on the right side. The curative effects between two groups were evaluated before and after operation, including the success rate of reduction, the duration of reduction, the distance from successful reduction to injury, complications and functional rehabilitation(Constant score of shoulder joint).@*RESULTS@#The success rates of reduction in experimental group and control group were 92.86%(26/28) and 67.86% (19/28), respectively, and the difference was statistically significant (P<0.05). The duration of simple reduction was (4.25±2.13) min and ( 6.31±1.69) min, the difference was statistically significant (P<0.05);the time from successful reduction to injury was (9.16±0.94) h and (8.94±1.31) h, respectively, with no significant difference(P>0.05). There were no complications such as vascular nerve injury and fracture in experimental group, 2 cases of axillary nerve injury and 1 case of humeral head fracture in control group. Constant scores of shoulder joint between experimental group and control group were (92.34±5.62) points and (90.91±4.73) points, respectively, with no significant difference (P>0.05).@*CONCLUSION@#For patients with irreducible subcoracoid dislocation of the shoulder joint with Hill-Sacks injury, the countertraction method under anesthesia of the shoulder joint cavity achieved a higher success rate and few complications.

Immediate postoperative color Doppler ultrasonography on the diagnosis of hemorrhagic complications of liver biopsy and its directed compression hemostasis / 中华肝脏病杂志

Objective: To study the diagnostic value of immediate color Doppler ultrasonography on traumatic hepatic hemorrhage after tissue sampling with ultrasound-guided liver biopsy and the clinical effect of its-directed local compression hemostasis at puncture-site. Methods: 132 hospitalized patients with various liver diseases underwent ultrasound-guided hepatic puncture-biopsies, including 61 cases with diffuse parenchymal and 71 cases with focal liver lesions. Immediate postoperative color Doppler ultrasonography was performed following liver biopsy. Abnormal blood flow signal was observed at hepatic puncture biopsy site, and if there were hemorrhagic signals, ultrasound-directed local compression hemostasis was performed until the bleeding signal disappeared. F-test and Chi-square test were used for statistical analysis. Results: Immediate color Doppler ultrasonography showed traumatic hemorrhage in 36.1% (22/61) and 40.8% (29/71) cases of diffuse liver disease and focal liver disease group, respectively. All hemorrhagic signals were eventually disappeared after ultrasound-directed local compression hemostasis. The median hemostasis time was 2 min in both groups, and there was no statistically significant difference in bleeding rate and hemostasis time between the two groups (P>0.05). There were no serious complications and deaths. Conclusion: Traumatic hepatic hemorrhage along the needle puncture tract is a common accompanying condition during liver biopsy. Immediate postoperative color Doppler ultrasonography can trace bleeding signals in timely manner and direct effective compression hemostasis, so it should be used routinely to help avoid occurrence of severe hemorrhagic complications.

Clinical application of bipolar tweezers-clamp for hepatic parenchymal transection / 中华外科杂志

Objective: To investigate the clinical value of the bipolar tweezers-clamp for the hepatic parenchymal transection in the resection of hepatocellular carcinoma. Methods: From January 2020 to January 2021,63 patients with the hepatocellular carcinoma for hepatectomy at Department of Hepatopancreatobiliary Surgery,Yuebei People's Hospital Affiliated to Shantou University Medical College were analyzed retrospectively.According to the different instruments used in the hepatic parenchymal transection,the patients were divided into bipolar tweezers-clamp group and ultrasonic scalpel group.There were 32 patients in bipolar tweezers-clamp group,with age of (55.5±10.5)years(range:37 to 78 years),including 22 males and 10 females,tumor size was (6.0±3.4)cm(range:2.4 to 13.4 cm). There were 6 patients with portal vein tumor thrombus and 5 patients with portal hypertension. There were 31 patients in ultrasonic scalpel group,with aged(57.8±10.1)years(range:37 to 79 years),including 27males and 4 females,tumor size was(7.9±5.1)cm(range: 2.4 to 21.3 cm),3 patients with portal vein tumor thrombus and 2 patients with portal hypertension. The preoperative baseline data,operation time,blood loss,postoperative liver function and the complications were compared between two groups using t test,χ2 test and Fisher exact probabilityrespectively. Results: The operation was successfully completed in both groups.Compared with the ultrasonic scalpel group,the operation time was significantly shorter((219.3±76.4)minutes vs.(294.0±100.8)minutes,t=-3.322,P=0.002),the blood loss was less((250(475)ml vs. 500(1 050)ml,t=-2.307,P=0.026),the concentrate red blood cells transfusion volume was less(0.92(0.88)U vs. 2.32(4.00)U,Z=-1.987,P=0.047) in the bipolar tweezers-clamp group.The postoperative serum ALB level was higher in the bipolar tweezers-clamp group than that in the ultrasonic scalpel group((33.5±6.1)g/L vs. (29.5±4.2)g/L,t=3.226,P=0.020) on postoperative day 1;((35.7±4.5)g/L vs.(30.1±3.2)g/L,t=5.575,P<0.01) on postoperative day 3;((33.2±3.7)g/L vs. (31.0±4.4)g/L,t=3.020,P=0.004) on postoperative day 7. There was no significant difference in serum ALT,TBIL and PT level between the two groups(all P>0.05).No postoperative bile leakage occurred in both groups.The postoperative complications occurred in 8 cases(25.0%)in the bipolar tweezers-clamp group,including liver failure in one,and in 11 cases(35.5%)in the ultrasonic scalpel group,including liver failure in two(P>0.05). Conclusion: The bipolar tweezers-clamp is a safe and reliable method for the hepatic parenchymal transaction,which is quick and less bleeding during the hepatic resection.

Real-world study on the efficacy and prognostic predictive biomarker of patients with metastatic non-small cell lung cancer treated with programmed death-1/programmed death ligand 1 inhibitors / 中华肿瘤杂志

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

Differential diagnosis of gallbladder polypoid lesions by micro-flow imaging / 南方医科大学学报

OBJECTIVE@#To explore the value of micro-flow imaging (MFI) in evaluating blood flow characteristics and differential diagnosis of gallbladder polypoid lesions.@*METHODS@#We retrospectively analyzed the clinical data and ultrasound images of 73 patients with gallbladder polypoid lesions, including 24 patients with pathologically confirmed neoplastic polyps (n=24) and 49 with non-neoplastic polyps (n=49). All the patients underwent conventional ultrasound, MFI and contrast enhanced ultrasound (CEUS) before cholecystectomy. The blood flow characteristics of the lesions in color Doppler flow imaging (CDFI) and MFI were compared, and the consistency of the findings by these two modalities with those of CEUS were evaluated by weighted Kappa consistency test. The diagnostic performance of MFI for gallbladder polypoid lesions was assessed.@*RESULTS@#There were significant differences between MFI and CDFI in the evaluation of blood flow characteristics of gallbladder polypoid lesions (χ2=37.684, P < 0.001). MFI showed better performance than CDFI in displaying the blood flow characteristics of the polyps. The consistency in the findings was 0.118 between CDFI and CEUS and 0.816 between MFI and CEUS. The sensitivity, specificity and accuracy of MFI in distinguishing neoplastic polyps from non-neoplastic polyps were 75.00%, 93.88% and 87.67%, respectively.@*CONCLUSION@#MFI has a good consistency with CEUS in displaying the blood flow characteristics of gallbladder polypoid lesions and can accurately distinguish neoplastic polyps from non-neoplastic polyps, thus providing new ultrasound diagnostic evidence to support clinical decisions on optimal treatments of gallbladder polypoid lesions.

Effect of Jiedu Huayu Granules on Inflammatory State of Patients with Chronic Hepatic Failure with Toxic Heat and Stasis Syndrome / 中国实验方剂学杂志

ObjectiveTo evaluate the curative effect of Jiedu Huayu granules （JDHY） in the treatment of chronic liver failure （CLF） with the syndrome of toxic heat and stasis and investigate the influence on the inflammatory state. MethodA total of 136 patients were randomly divided into a control group and an observation group with 68 cases in each group. In addition to the comprehensive western medicine treatment， patients in the control group received Yinchen Haotang granules orally at 1 dose/day and those in the observation group received JDHY at 10 g/time，3 times/day. The treatment lasted for eight weeks. The endotoxin （ET），diamine oxidase （DAO），aromatic amino acids （AAA），branched chain amino acids （BCAA），blood ammonia，calcitonin （PCT），tumor necrosis factor-α （TNF-α），interleukin （IL）-1，IL-6，IL-17，regulatory T cells （Treg cells），helper T cells 17 （Th17），Th17/Treg ratio，total bilirubin （TBil），albumin （Alb），alanine aminotransferase （ALT），aspartate aminotransferase （AST），prothrombin activity （PTA）， and D-dimer （D-D） levels before and after treatment were detected. The Child-Pugh grading scores of liver function， toxic heat and stasis syndrome scores， and the model scores of end-stage liver disease（MELD） before and after treatment were recorded. The fatality rate and survival were recorded at the follow-up for 48 weeks. ResultCompared with the control group after treatment， the observation group showed decreased ET，DAO， and blood ammonia， increased BCAA/AAA ratio （P<0.01）， reduced PCT，TNF-α，IL-1，IL-6， and IL-17 （P<0.01）， elevated Treg cells， dwindled Th17 and Th17/Treg ratio （P<0.01）， diminished TBil，ALT，AST， and D-D levels， and up-regulated Alb and PTA（P<0.01）. The Child-Pugh grading score，MELD score， and toxic-heat and stasis syndrome score of the observation group were lower than those of the control group （P<0.01）. The total response rate in the observation group was 93.65% （59/63），which was higher than 79.03% （49/62） in the control group （χ2=5.683，P<0.05）. The fatality rate of the observation group eight weeks after treatment was 6.35% （4/63），which was lower than 19.35% （12/62） of the control group （χ2=4.757，P<0.05）. There was no significant difference in mortality between the two groups 16，24， and 48 weeks after treatment. As revealed by the Log-rank test，the difference in survival curves between the two groups was not statistically significant. ConclusionJDHY can remove toxins from the body，regulate immune function，relieve inflammation，improve liver function， and reduce the severity of the disease in CLF patients with the syndrome of toxic heat and stasis. It is significant in clinical efficacy and worthy of clinical application.