Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

BACKGROUND: At present, the research progress of targeted therapy for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations in lung adenocarcinoma is very rapid, which brings new hope for the treatment of advanced lung adenocarcinoma patients. However, the specific imaging and pathological features of EGFR and ALK gene mutations in adenocarcinoma are still controversial. This study will further explore the correlation between EGFR, ALK gene mutations and imaging and pathological features in invasive lung adenocarcinoma. METHODS: A total of 525 patients with lung adenocarcinoma who underwent surgery in our center from January 2018 to December 2019 were included. According to the results of postoperative gene detection, the patients were divided into EGFR gene mutation group, ALK gene mutation group and wild group, and the EGFR gene mutation group was divided into exon 19 and exon 21 subtypes. The pathological features of the mutation group and wild group, such as histological subtype, lymph node metastasis, visceral pleural invasion (VPI) and imaging features such as tumor diameter, consolidation tumor ratio (CTR), lobulation sign, spiculation sign, pleural retraction sign, air bronchus sign and vacuole sign were analyzed by univariate analysis and multivariate Logistic regression analysis to explore whether the gene mutation group had specific manifestations. RESULTS: EGFR gene mutation group was common in women (OR=2.041, P=0.001), with more pleural traction sign (OR=1.506, P=0.042), and had little correlation with lymph node metastasis and VPI (P>0.05). Among them, exon 21 subtype was more common in older (OR=1.022, P=0.036), women (OR=2.010, P=0.007), and was associated with larger tumor diameter (OR=1.360, P=0.039) and pleural traction sign (OR=1.754, P=0.029). Exon 19 subtype was common in women (OR=2.230, P=0.009), with a high proportion of solid components (OR=1.589, P=0.047) and more lobulation sign (OR=2.762, P=0.026). ALK gene mutations were likely to occur in younger patients (OR=2.950, P=0.045), with somking history (OR=1.070, P=0.002), and there were more micropapillary components (OR=4.184, P=0.019) and VPI (OR=2.986, P=0.034) in pathology. CONCLUSIONS The EGFR and ALK genes mutated adenocarcinomas have specific imaging and clinicopathological features, and the mutations in exon 19 or exon 21 subtype have different imaging features, which is of great significance in guiding the clinical diagnosis and treatment of pulmonary nodules.
Adenocarcinoma of Lung/genetics* ; Aged ; Anaplastic Lymphoma Kinase/genetics* ; ErbB Receptors/genetics* ; Female ; Genes, erbB-1 ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Tomography, X-Ray Computed/methods*

BACKGROUND: At present, more and more studies predict invasive adenocarcinoma (IAC) through three-dimensional features of pulmonary nodules, but few studies have confirmed that three-dimensional features have more advantages in diagnosing IAC than traditional two-dimensional features of pulmonary nodules. This study analyzed the differences of chest computed tomography (CT) features between IAC and minimally invasive adenocarcinoma (MIA) from three-dimensional and two-dimensional levels, and compared the ability of diagnosing IAC. The non-invasive adenocarcinoma group includes precursor glandular lesions (PGL) and minimally invasive adenocarcinoma (MIA). METHODS: The clinical data of 1,045 patients with ground glass opacity (GGO) from January to December 2019 were collected. Then the correlation between preoperative CT image characteristics and pathological results were analyzed retrospectively. The independent influencing factors for the identification of IAC were screened out according to two-dimensional and three-dimensional classification by multivariate Logistic regression and the cut-off point for the identification of IAC was found out through the receiver operating characteristic (ROC) curve. At last, the ability of diagnosing IAC was evaluated by Yoden index. RESULTS: The diameter of nodule, the diameter of solid component, the diameter of mediastinal window nodule in two-dimensional factors, and the volume of nodule, the volume of solid part and the average CT value in three-dimensional factors were independent risk factors for the diagnosis of IAC. These factors were arranged by Yoden index: solid partial volume (0.601)>nodule volume (0.536)>solid component diameter (0.525)>nodule diameter (0.518)>mediastinal window nodule diameter (0.488)>proportion of solid component volume (0.471)>1-tumor disappearance ratio (TDR) (0.468)>consolidation tumor ratio (CTR) (0.394)>average CT value (0.380). CONCLUSIONS The CT features of three-dimensional are better than two-dimensional in the diagnosis of IAC, and the size of solid components is better than the overall size of nodules.
Humans ; Lung Neoplasms/pathology* ; Retrospective Studies ; Neoplasm Invasiveness ; Multiple Pulmonary Nodules/diagnostic imaging* ; Adenocarcinoma/pathology*

P1B-ATPases are a group of proteins that can transport heavy metal ions across membranes by hydrolyzing ATP and they are a subclass of the P-type ATPase family. It was found that P1B-ATPases are mainly responsible for the active transport of heavy metal ions in plants and play an important role in the regulation of heavy metal homeostasis in plants. In this paper, we dissusses the mechanism of P1B-ATPases from the structure and classification of P1B-ATPases, and review the current research progress in the function of P1B-ATPases, in order to provide reference for future research and application of P1B-ATPases in improving crop quality and ecological environment management.
Adenosine Triphosphatases/metabolism* ; Biological Transport ; Metals, Heavy ; Plants/enzymology*

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34- ~ 21.15) mmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31- ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) mmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) mmol/L, respectively. Conclusion The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.

Objective To compared the macular blood flow parameters among myopic choroidal neovascularization (mCNV), high myopia (HM) and normal subjects.Methods Retrospective study. Forty patients (40 eyes) diagnosed as mCNV (mCNV group) in the Eye Hospital of Wenzhou Medical University at Hangzhou from June 2016 to November 2018, age-matched, sex-matched and diopter-matched 40 HM patients (40 eyes, HM group), age-matched and sex-matched 40 healthy persons (40 eyes, normal group) were enrolled in this study. Retina superficial and deep vessel density, the area of foveal avascular zone (FAZ), a-circularity index (AI) and vessel density around the 300 μm width of the FAZ region (FD) on macular 3 mm×3 mm scan on OCTA of 3 groups were compared.Results There were significant differences in the average retina superficial, deep vessel density, the area of FAZ, AI and FD among 3 groups (F=24.82, 9.18, 3.58, 7.68, 14.15;P<0.05). The average retina superficial and deep vessel density and FD in mCNV group were lower than those in HM group (P<0.05). The average retina superficial and deep vessel density and FD in HM group were lower than those in control group (P<0.05). The average area of FAZ in mCNV group was smaller than that in control group (P<0.05). The average AI in mCNV group was less than that in the other 2 groups (P<0.05). Conclusions The retina superficial, deep vessel density and FD decreased, the area and the form of FAZ remained unchanged in HM subjects comparing with normal subjects. While retina superficial, deep vessel density and FD decreased more, the area of FAZ reduced, the form of FAZ tend to be irregular in mCNV.

AIM:To analyze the correlation between serum angiotensin-converting enzyme 2 (ACE2) levels and different stages of coronary heart disease (CHD), and to explore the change of serum ACE2 level during the development of CHD.METHODS:The control group included 85 non-CHD samples, and 174 CHD samples were divided into light stenosis (ls-CHD, stenosis degree <50%) group, moderate stenosis (ms-CHD, stenosis degree 50%~75%) group and severe stenosis (ss-CHD, stenosis degree ≥75%) group.The ACE2 level in each serum sample was detected by ELISA.The relationship between the ACE2 level and the development of coronary heart disease was explored by statistical analysis of serum ACE2 levels in different stages of CHD.RESULTS:The serum ACE2 levels in ls-CHD group, ms-CHD group and ss-CHD group were all higher than that in control group.The more severe the coronary artery stenosis existed, the higher the ACE2 level was observed.The serum ACE2 level in the males was higher than that in the females.In a single sex, the serum ACE2 levels in ls-CHD group, ms-CHD group and ss-CHD group were higher than that in control group with significant differences.Regression analysis found that sex, diabetes and CHD were associated with the serum ACE2 levels.Among them, sex and CHD were the independent factors to affect serum ACE2 levels.CONCLUSION:The serum ACE2 level of males was higher than that of females.Compared with the non-CHD samples, the serum ACE2 level of CHD patients was higher than that of the non-CHD samples.During the development of coronary heart disease, the serum ACE2 level increased constantly.

Objective To detect the cellular immune and humoral immune function in infants with Mycoplasma pneumoniae(Mp) infection,and to study its change regularity and the related clinical indexes.Methods The peripheral blood samples were collected from infantile patients with MP infection.The expression of CD3,CD4 and CD8 on the surface of T lymphocyte(T-cell)were detec-ted by the flow cytometry and the concentrations of IgG,IgA and IgM in serum were detected by the automatic biochemistry analy-zer.At the same time the normal control group was set up.Results The proportion of CD3 + and CD4 + T-cell,CD4 +/CD8 + ratio and the concentration of IgG,IgA in the patient group were significantly lower than those in the control group,while the concentra-tion of IgM in the patient group were significantly lower than those in the normal children.The concentration of IgM was higher than that in the normal children;the proportion of peripheral blood CD4 + T-cell and the concentration of IgM in the low-copy group were significantly lower than those in the high-copy group.Conclusion The immune status in children with Mp infection has obvi-ous change.The immune function of T-cell is suppressed.the humoral immune function has certain turbulence.

Objective To analyze the clinical and dosimetric risk factors for acute radiation esophagitis (ARE) in non-small cell lung cancer (NSCLC) patients treated with three-dimensional conformal radiotherapy (3D-CRT),and to find significant risk factors for clinical therapy.Methods A total of 102 NSCLC patients treated with 3D-CRT were retrospectively analyzed.ARE was scored according to the Radiation Therapy Oncology Group (RTOG) criteria with grade 2 or worse.Patients were divided into non-concurrent chemoradiotherapy group and concurrent chemoradiotherapy group.The clinical and dosimetric factors associated with grade 2 or worse ARE were analyzed using univariate logistic regression,multivariate logistic analysis and receiver operating characteristic ( ROC ) curve.Results There were no grade 4 or5 ARE observed in the 102 patients.Nineteen developed grade 2,15 developed grade 3.In nonconcurrent chemoradiotherapy group,multivariate analysis showed that V55 was the only risk factor of grade 2/3 ARE.For ROC curve analysis,the cut-off point of V55 was 16.0 while the area under ROC curve was 0.870 ( 95 ％ CI:0.782 - 0.957,P ＜ 0.05 ).In concurrent chemoradiotherapy group,multivariate analysis showed that V35 and chemotherapy regimens during radiotherapy were risk factors of grade 2/3 ARE.The cut-off point of V35 was 23.75 while the area under ROC curve was 0.782 (95％ CI:0.636 -0.927,P ＜0.05).Vinorelbine and cisplatin regimen showed low incidence of ARE contrast with gemcitabine/docetaxel and cisplatin regimens (33.3％ and 66.7％ ).Conclusions V55 is the only statistically significant risk factor associated with grade 2 or worse ARE for patients who don't accepted concurrent chemotherapy.V35 and chemotherapy regimens during radiotherapy are statistically significant risk factors associated with grade 2 or worse ARE for patients who accept concurrent chemotherapy.Vinorelbine and cisplatin regimen during radiotherapy shows low incidence of ARE.

Objective To explore the influence factors on hepatitis B virus (HBV) relapse after nucleos(t)ide analogues (NA) withdrawal in the chronic hepatitis B (CHB) patients who met NA cessation criteria. Methods Eighty-one consecutive CHB patients were treated with NA, 38 with lamivudine (LAM), 25 with adefovir dipivoxil (ADV), 12 with entecavir (ETV), 6 with LAM +ADV. Among recruited patients, 40 were hepatitis B virus e antigen (HBeAg) positive, 41 were HBeAg negative, 67 of them were initial treatment, 14 were retreatment due to resistance to NA at baseline. The treatment was discontinued after meeting China therapeutic end-point criteria. HBV DNA, HBV serological markers, alanine aminotransferase (ALT) were measured respectively at baseline, every month before virological response, every 3 months after virological response, every month within first 6 months and every 2 months over 6 months after drugs withdrawal. Twelve probable influence factors on relapse which were sex, age, HBV family history, baseline HBV DNA,baseline HBeAg status, baseline ALT, virological response time, total duration of treatment, duration of additional treatment, the level of hepatitis B virus surface antigen (HBsAg) at cessation therapy,initial treatment or retreatment, drug category were analyzed with univariate, multivariate Cox regression modle and stratified analysis. The cumulative relapse was calculated by the Kaplan-Meier method. Results A total of 36 patients (44. 4%) relapsed within 1 year. Initial treatment or retreatment, HBV family history, virological response time, the level of HBsAg at cessation therapy were independent risk factors. The relapse rate of retreatment was higher than that of initial treatment (78.6% vs 37. 3% , χ2 = 7. 983, P = 0. 005) , those of patients with HBV family history higher than without family history (64. 5% vs 15.0%, χ2 =12. 096,P = 0.002), those of patients obtained virological response within 3 months lower than after 3 months(34. 0% vs 64. 3% , χ2 =6. 823,P=0. 009) , those of patients with HBsAg≤150 μg/L at cessation therapy lower than >150 μg/L(27. 6% vs 53. 8%, χ2=5. 199,P=0. 023). Conclusions Retreatment, HBV family history, later virological response and higher HBsAg level at cessation therapy are risk factors of relapse after NA withdrawal. Such patients should be treated with prolonged duration after meeting end-point criteria to strengthen the efficacy.