[Analysis of the efficacy and safety of dual immunotherapy in patients with driver gene and programmed death ligand-1 double negative advanced non-small cell lung cancer].

Objective: To discuss the efficacy and safety of the dual immunotherapy of nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) who are double negative for driver gene and programmed death-ligand 1 (PD-L1) expression. Methods: We conducted a retrospective collection of clinical data for 61 patients with advanced NSCLC who were negative for both driver genes and PD-L1 and received dual immunotherapy with nivolumab plus ipilimumab at the First Affiliated Hospital of Guangzhou Medical University from January 2019 to June 2023. Based on treatment conditions, patients were divided into first-line and non-first-line dual immunotherapy groups. Patients were followed up monthly, with the follow-up period ending on October 1, 2023. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute in the United States. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in progression-free survival (PFS) and overall survival (OS) between first-line and non-first-line dual immunotherapy patients. The influence factors of PFS were analyzed using a multivariate Cox proportional hazards regression model. Results: Among the 61 NSCLC patients, 49 were male (80.3%), with an age range of 23-88 years [(65.3±7.4) years]. There were 14 cases (23.0%) classified as stage ⅢC and 47 cases (77.0%) classified as stage Ⅳ according to TNM staging. Forty cases (65.6%) received non-first-line treatment. The objective response rate (ORR) was 24.6% (15/61), and the disease control rate (DCR) was 52.5% (32/61). All 61 patients were followed up, with a median follow-up time of 17.8 months. The median PFS was 6.0 months (95%CI: 5.5-6.4 months), and the median OS was 17.0 months (95%CI: 14.8-19.2 months). For patients receiving first-line dual immunotherapy, the median PFS was longer than for those receiving non-first-line dual immunotherapy [7.0 months (95%CI: 6.0-7.9 months) vs 4.0 months (95%CI: 3.3-4.6 months), P<0.001]; similarly, the median OS for patients receiving first-line dual immunotherapy was longer than for those receiving non-first-line dual immunotherapy [19.0 months (95%CI: 18.1-19.9 months) vs 13.0 months (95%CI: 10.8-15.1 months), P<0.001]. Multivariate Cox risk regression model analysis showed that distant tumor metastasis (HR=1.414, 95%CI: 1.253-1.725), non-first-line dual immunotherapy (HR=1.412, 95%CI: 1.184-1.652), and tumor mutation burden<10 mut/Mb (HR=1.328, 95%CI: 1.151-1.546) were risk factors for PFS, while non-squamous carcinoma (HR=0.917, 95%CI: 0.823-0.984) was a protective factor for PFS. Immune-related adverse reactions occurred in 41 cases (67.2%), including 21 cases (32.8%) of grade 3-4 adverse reactions. Eight cases (13.1%) discontinued treatment, and there were no deaths. Conclusions: Dual immunotherapy with nivolumab plus ipilimumab can be a treatment option for driver gene and PD-L1 double-negative advanced NSCLC. Distant tumor metastasis, non-first-line dual immunotherapy, and tumor mutation burden<10 mut/Mb are risk factors affecting patients' PFS, while non-squamous cell carcinoma is a protective factor affecting patients' PFS.

[Establishment of early warning indicators of SARS-CoV-2 Omicron variant in Tianjin].

In this study, Delphi method was used to conduct a questionnaire survey on 12 experts to determine the indicators system and the corresponding weight for early warning features of SARS-CoV-2 Omicron in Tianjin.The positive indexes of experts in three rounds of consultations were both 100%. The experts' authority coefficient was 0.79. The Kendall's W coordination coefficients were 0.375, 0.356 and 0.385 respectively (all P<0.05). The indicators system for early warning features of 2019-nCoV Omicron variant had 5 first-level indicators, 10 second-level indicators and 52 third-level indicators. The weight of each indicator was also determined.

[CXCL5 inhibits tumor immune of lung cancer via modulating PD1/PD-L1 signaling].

Objective: To investigate the role of CXCL5 in tumor immune of lung cancer and to explore the potential molecular mechanisms. Methods: A total of 62 cases of patients with lung cancer admitted in the First Affiliated Hospital of Henan University from May 2018 to December 2019 were recruited as study object. Another 20 cases of patients with pulmonary infectious diseases and 20 cases of healthy control were selected as control. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of CXCL5 in patients with lung cancer, pulmonary infectious diseases and healthy control. Immunohistochemical staining (IHC) was used to detect the expressions of CXCL5 and PD-1/PD-L1 in tumor and paracarcinoma tissues of patients with lung cancer. Pearson correlation analysis was used to evaluate the correlation between CXCL5 and PD-1 in tumor and paracarcinoma tissues of patients with lung cancer. Lewis cells either expressing CXCL5 or vector plasmids were used to establish C57BL/6J mice model of lung cancer, and all mice were then divided into vehicle and PD-1 antibody treatment groups, 10 mice for each group. The mice survival and tumor growth curves were recorded. IHC was used to evaluate the expressions of CXCL5, PD-1 as well as the proportions of CD8(+) T and Treg cells in xenograft tumor tissues. Results: In patients with lung cancer, the serum level of CXCL5 [(351.7±51.5) ng/L] was significant higher than that in patients with pulmonary infectious diseases and healthy control [(124.7±23.4) ng/L, P<0.001]. The expression levels of CXCL5 (0.136±0.034), CXCR2 (0.255±0.050), PD-1 (0.054±0.012) and PD-L1 (0.350±0.084) in tumor were significant higher than those in paracarcinoma normal tissues [(0.074±0.022), (0.112±0.023), (0.041±0.007) and (0.270±0.043) respectively, P<0.001]. CXCL5 was significant positively correlated with PD-1 in tumor tissues of lung cancer (r=0.643, P<0.001), but not correlated with PD-1 in paracarcinoma tissues(r=0.088, P=0.496). The vector control group, CXCL5 overexpression group, vector control + anti-PD-1 antibody treatment group and CXCL5 overexpression + anti-PD-1 antibody treatment group all successfully formed tumors in mice, while CXCL5 overexpression increased the tumor growth significantly (P<0.01), which was abrogated by the treatment of anti-PD-1 antibody. CXCL5 overexpression decreased the mice survival time significantly (P<0.01), this effect was also abrogated by the treatment of anti-PD-1 antibody. The proportion of CD8(+) T cells in CXCL5 overexpression group [(10.40±2.00)%] was significant lower than that in vector control group [(21.20±3.30)%, P=0.002]. The proportion of CD4(+) Foxp3(+) Treg cells in CXCL5 overexpression group [(38.40±3.70)%] was significant higher than that in vector control group [(23.30±2.25)%, P<0.001]. After the treatment of anti-PD-1 antibody, no significant difference were observed for the proportion of CD8(+) T cells [(34.10±5.00)% and (33.40±4.00)% respectively] and Treg cells [(14.70±3.50)% and (14.50±3.30)% respectively] in xenograft tumor tissues between CXCL5 overexpression+ anti-PD-1 antibody treatment group and vector control + anti-PD-1 antibody treatment group (P>0.05). Conclusion: The expressions of CXCL5 and PD-1/PD-L1 are all increased significantly in the tumor tissues of patients with lung cancer, CXCL5 may inhibit tumor immune of lung cancer via modulating PD-1/PD-L1 signaling.

[The correlation study on human respiratory syncytial virus daily incidence and meteorological parameters in the main urban area of Chongqing from 2009 to 2019].

Objective: To explore the relationship between the daily incidence of human respiratory syncytial virus (HRSV) and meteorological parameters in the main urban area of Chongqing. Methods: This study took 3 107 children hospitalized with acute lower respiratory tract infections from June 2009 to June 2019 in department of Respiratory medicine, Children's Hospital of Chongqing Medical University (CHCMU). Nasopharyngeal aspirate (NPA) was collected on the day of admission to detect HRSV and common respiratory virus; combined with the meteorological data of the main urban area of ​​Chongqing during the same period, the correlation and distribution lag nonlinear model analysis of the daily incidence of HRSV and meteorological parameters were carried out. Results: Among 3 107 children, HRSV positive accounted for 34.53% (1 073 cases), the age was 6 (3, 13) months, and males accounted for 64.31% (690 cases). The daily incidence of HRSV was negatively correlated with minimum temperature (r=-0.220, P<0.001), maximum temperature (r=-0.221, P<0.001), average temperature (r=-0.221, P<0.001) and precipitation (r=-0.052, P<0.001), and positively correlated with sunshine time (r=0.011, P<0.001) and average relative humidity (r=0.095, P<0.001). Compared with the reference temperature (20 ℃), when the lowest temperature of 6-10 ℃ lags for 4-8 d, the RR value of HRSV was 1.11-1.14, and when the lowest temperature of 5-19 ℃ lags for 5 d and 2-19 ℃ lags for 10 d, the RR values were 1.02-1.14 and 1.00-1.03. When the cumulative lag is 5, 10, 15 and 21 d, compared with the reference temperature (20 ℃), the RR (95%CI) values at the lowest temperature of 10.4 ℃ were 1.93 (1.08-3.46), 3.49 (1.64-7.45), 5.00 (2.01-12.46) and 6.69 (2.18-20.48); the RR (95%CI) values of the lowest temperature of 22.1 ℃ were 0.87 (0.77-0.98), 0.77 (0.66-0.90), 0.74 (0.62-0.89) and 0.68 (0.55-0.85). In the cumulative effect, compared with the reference temperature (20 ℃), the gender stratification showed that the maximum RR (95%CI) values of the lowest temperature for boys and girls under different lag days were 7.24 (1.84-28.51) and 2.19 (1.07-4.46), the age stratification showed that the maximum RR (95%CI) values of the lowest temperature for children<6 months old and children ≥6 months old under different lag days were 4.72 (1.05-21.23) and 11.98 (1.70-84.35). Conclusions: In the main urban area of Chongqing, the daily incidence of HRSV in children is correlated with climatic parameters. Among them, the lowest temperature has a delayed and cumulative effect on HRSV infection. 6-10 ℃ has a greater impact on the incidence of HRSV when the lag is 4-8 days. The effect has a more obvious impact on the incidence of HRSV in boys and children ≥ 6 months.

[Psychological and behavioral functioning of children and adolescents during long-term home-schooling].

Objective: To study the characteristics and risk factors of psychological and behavioral problems of children and adolescents of different ages and genders in long-term home-schooling during the coronavirus disease-2019 pandemic. Further, to provide scientific basis for more targeted psychological intervention and coping strategies in the future. Methods: A cross-sectional survey using an online questionnaire was conducted on students aged 6-16 years old in five representative cities of North (Beijing), East (Shanghai), West (Chongqing), South (Guangzhou) and Middle (Wuhan) in China. In this study, the social behavior and psychological abnormalities which was defined as the positive of any dimension were investigated in multiple dimensions during long-term home-schooling. The influencing factors of psycho-behavioral problems were analyzed by Logistic regression, and the confounding factors were corrected with graded multivariable adjustment. Results: A total of 6 906 valid questionnaires were collected including 3 592 boys and 3 314 girls, of whom 3 626 were children (6-11 years old) and 3 280 were adolescents (12-16 years old). The positive detection rate of psychosocial-behavioral problems were 13.0% (900/6 906) totally, 9.6% (344/3 592) in boys and 16.8% (556/3 314) in girls respectively, and 7.3%(142/1 946) in boys aged 6-11, 14.0%(235/1 680) in girls aged 6-11, 12.3%(202/1 646) in boys aged 12-16, 19.6%(321/1 634) in girls aged 12-16 respectively. There were significant differences between the psychological problems group and the non-psychological problems group in gender, parent-offspring conflict, number of close friends, family income change, sedentary time, homework time, screen exposure time, physical activity, dietary problems (χ²=78.851, 285.264, 52.839, 26.284, 22.778, 11.024, 10.688, 36.814, 70.982, all P<0.01). The most common symptoms in boys aged 6-11 years were compulsive activity, schizoid and depression, in girls aged 6-11 years were schizoid/compulsive activity, hyperactivity and social withdrawal, in boys aged 12-16 years were hyperactivity, compulsive activity and aggressive behavior, and in girls aged 12-16 years were schizoid, anxiety/compulsive activity and depression/withdrawal, respectively. After graded multivariable adjustment, besides the common risk factors, homework time and online study time were the risk factors of 6-11 years old groups [boys OR(95%CI): 1.750 (1.32-2.32), 1.214(1.00-1.47), girls: 1.579(1.25-1.99), 1.222(1.05-1.42), all P<0.05], videogames time were the risk factors of 12-16 years old groups [ boys: 2.237 (1.60-3.13), girls: 1.272 (1.00-1.61), all P<0.05]. Conclusions: Some children and adolescents may have psychological and behavioral problems during long-term home-schooling. The psychological and behavioral manifestations differed in age and gender subgroups, which deserve special attention in each subgroups. Schools, families and specialists should actively provide precise psychological support and comprehensive intervention strategies according to special features and risk factors.

[Exploration of the treatment model for patients with advanced non-small cell lung cancer complicated with chronic obstructive pulmonary disease based on real-world data].

Objective: To explore whether combining treatment of chronic obstructive pulmonary disease (COPD) with anti-tumor therapy is better than that of tumor treatment alone in advanced non-small cell lung cancer (NSCLC) patients with COPD in the real world. Methods: The clinical data of 101 patients with advanced NSCLC complicated with COPD from January 1, 2015, to December 31, 2017, in the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively, including 99 males and two females, aged from 52 to 84 years[average (67±8) years]. Among the patients, 90 (89.1%) were smokers, with an average pack-year smoking index of (47±4) . The patients were divided into observation and control groups, depending on whether they received standardized anti-COPD supportive treatment. In the observation group, there were 36 patients, including 35 males and one female, aged from 54 to 84 years[ average (67±8) years], with an average pack-year of smoking (47±4). There were 65 patients in the control group, including 64 males and one female, aged from 52 to 83 years [average (67±8) years], with an average pack-year of smoking 47±4. There was no significant difference in the baseline data between the two groups. The primary outcome measures included the Objective response rate (ORR), disease control rate (DCR), disease-free survival (PFS), and overall survival (OS) of the two groups. An unpaired t-test was used to compare continuous variables between the observation and control groups. The Pearson chi-square test was used to compare categorical variables between the two groups. Kaplan-Meier survival curves were used to evaluate the median PFS and median OS of patients, and the log-rank test was used to assess differences between groups. Result: The ORR of the observation group and the control group was 22.6% (7 cases) and 22.2% (11 cases), respectively, with no significant difference (χ(2)=0.01, P=0.971). The DCR between the observation group and the control group was 58.1% (19 cases) and 57.8% (27 cases), with no significant difference (χ(2)=0.02, P=0.889). Median PFS in the observation group was 6.0 months, which was better than the 3.5 months in the control group (χ(2)=3.947, P<0.05). The median OS of the observation group was 18.0 months, which was better than the 15.0 months of the control group (χ(2)=4.083, P<0.05). Conclusions: Compared with the treatment of tumors alone, combination of anti-tumor therapy with anti-COPD therapy showed longer PFS and OS in patients with advanced NSCLC complicated with COPD.

[Analysis of adverse pregnancy outcomes and related factors in pregnant women with syphilis infection in Guangxi of China, 2014-2018].

Objective: To analyze the status and related factors of adverse pregnancy outcomes in pregnant women with syphilis infection in Guangxi Zhuang Autonomous Region. Methods: A total of 9378 pregnant women with syphilis infection who were diagnosed by Guangxi medical and health care institutions at all levels and were registered in the national "Management information system for mother-to-child transmission of AIDS, syphilis and hepatitis B" . The delivery date of these pregnant women were from 1 January 2014 to 31 December 2018, and their demographic characteristics, treatment, non-treponema pallidum titer, and pregnancy outcomes were collected. Multivariate logistic regression model was used to analyze the related factors of adverse pregnancy outcome. Results: The age of the pregnant women with syphilitic infection was (30.05±6.07) years old. There were 1 184 cases with an adverse pregnancy outcome. The incidence of adverse pregnancy outcome was 12.63%, and 83.30% (7 812 cases) of patients received syphilis treatment, of which 50.32% (3 931 cases) were treated with standard treatment. The results of multivariate analysis showed that, the probability of an adverse pregnancy outcome for a 35-year-old was higher than those of the <25 year old [OR (95%CI)=1.37(1.13-1.67)]. The possibility of the occurrence of an adverse pregnancy outcome in 1-2 times of delivery was lower than that of 0 times of delivery in the past, with the OR (95%CI) value was 0.81 (0.70-0.94). Compared with those who tested for syphilis in the early stages of pregnancy, patients with gestational weeks ≥ 28 weeks of initial examination were more likely to have adverse pregnancy outcomes, with the OR (95%CI) value was 1.54 (1.26-1.88). Compared with the first test titer level was <1:8, the probability of an adverse pregnancy outcome was higher in the titer of ≥1:8, with the OR (95%CI) value was 1.33 (1.12-1.57). There was a higher probability of an adverse pregnancy outcome in the untreated patients compared to the treatment of the syphilitic, with the OR (95%CI) value was 1.41(1.19-1.68). Patients with unregulated treatment were more likely to have adverse pregnancy outcomes than those with standardized treatment, with the OR (95%CI) value was 1.27 (1.09-1.47). Conclusion: Gestational weeks of first examination in pregnant women with syphilis infection, the first test titer, and the treatment condition were closely related to the occurrence of the adverse pregnancy outcome. Pregnant women with syphilis infection without treatment and unstandardized treatment were more likely to have adverse pregnancy outcomes than those of treatment and standardized treatment.

The embryonic and evolutionary boundaries between notochord and cartilage: a new look at nucleus pulposus-specific markers.

The adult nucleus pulposus (NP) and articular cartilage are similar in terms of their histocytological components and biomechanical functionalities, requiring a deep understanding of NP-specific markers to better evaluate stem-cell-based NP regeneration. Here, we seek to distinguish NP cells from articular chondrocytes (ACs), focusing on differences in their embryonic formation and evolutionary origin. Embryonically, NP cells are conservatively derived from the axial notochord, whereas ACs originate in a diversified manner from paraxial mesoderm and neural crest cells. Evolutionarily, although the origins of vertebrate NP and AC cells can be traced to similar structures within protostomia-like bilaterian ancestors, the distant phylogenetic relationship between the two groups of animals and the differences in the bodily origins of the tissues suggest that the tissues may in fact have undergone parallel evolution within the protostomia and deuterostomia. The numbers of supposedly NP-specific markers are increasing gradually as microarray studies proceed, but no final consensus has been attained on the specificity and physiology of "exclusive" NP markers because of innate variations among species; intrinsic expression of genes that destabilize the circadian clock; and cooperation by, and crosstalk among, different genes in terms of physiology-related phenotypes. We highlight the embryonic and evolutionary boundaries between NP and AC cells, to aid in recognition of the challenges associated with evaluation of the role played by nucleopulpogenic differentiation during stem-cell-based intervertebral disc regeneration.

Statin therapy on glycemic control in type 2 diabetic patients: A network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Statins are the cornerstone of primary and secondary prevention of cardiovascular diseases (CVDs) and are effective for the prevention of vascular events in diabetic patients. Diabetes mellitus is an important risk factor for CVDs .The majority of patients with diabetes mellitus benefits from statin therapy. According to the recent clinical guidelines of the American College of Cardiology and the American Heart Association, moderate-intensity or high-intensity statin therapy should be used as the primary prevention for individuals with diabetes mellitus, aged between 40 and 75 years and with low-density lipoprotein cholesterol (LDL-C) from 70 to 189 mg/dL. The objective of this review was to compare the associations of individual statins with their adverse effects on glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception through March 2017. There were included randomized controlled trials comparing statins with placebo or active comparators in patients with T2DM. The endpoints of interest were glycated haemoglobin A1C (HbA1C ) and fasting plasma glucose (FPG). We performed a pairwise meta-analysis and a network meta-analysis within a frequentist framework. The standard mean differences (SMD) and 95% confidence intervals (CI) were calculated. RESULTS: Twenty-three trials were included. A significant increase in HbA1c was detected in the pairwise meta-analysis when statins as a class were compared with placebo (SMD: 0.11). Moderate-intensity pitavastatin lowered HbA1c compared with moderate-intensity atorvastatin (SMD: -0.16), high-intensity atorvastatin (SMD: -0.77), moderate-intensity rosuvastatin (SMD: -0.16) and low-intensity pravastatin (SMD: -0.15). Moderate-intensity simvastatin lowered HbA1c compared with high-intensity rosuvastatin (SMD: -0.45) and high-intensity atorvastatin (SMD: -0.77). High-intensity atorvastatin elevated HbA1c compared with placebo (SMD: 0.63), moderate-intensity rosuvastatin (SMD: 0.50), low-intensity pravastatin (SMD: 0.51) and moderate-intensity atorvastatin (SMD: 0.50). Moderate-intensity pitavastatin has lowered FPG compared with placebo (SMD: -0.55), moderate-intensity rosuvastatin (SMD: -0.65), moderate-intensity atorvastatin (SMD: -0.65) and high-intensity atorvastatin (SMD: -1.25). High-intensity atorvastatin has elevated FPG compared with placebo (SMD: 0.70), moderate-intensity atorvastatin (SMD: 0.60), moderate-intensity rosuvastatin (SMD: 0.60) and moderate-intensity simvastatin (SMD: 0.90). WHAT IS NEW AND CONCLUSION: Statins were associated with an increase in HbA1c compared with placebo. In patients with T2DM, moderate-intensity pitavastatin improved the glycemic control whereas high-intensity atorvastatin worsened it. Appropriate statins should be administered for patients with diabetes mellitus.

Distribution and quantitative analysis of CIDEa and CIDEc in broiler chickens: accounting for differential fat deposition between strains.

1. Differences in the expression of CIDEa and CIDEc in 20 different tissues were examined. Both CIDEa and CIDEc mRNA transcripts were predominantly but variably expressed in white adipose tissue (WAT) but were also expressed at moderate levels in the kidney and liver and at lower levels in the ovary. Interestingly, among WAT types, both CIDEa and CIDEc were expressed at the lowest levels in heart coronary WAT. 2. To better understand the roles of CIDEa and CIDEc in the fat deposition of broiler chickens, the differences in lipid droplet (LD) size and mRNA levels of CIDEa and CIDEc between lean-type and fat-type broiler chicken lines were studied. LD sizes were larger in fat-type broiler lines, and CIDEa and CIDEc mRNA levels in white adipose, kidney and liver tissues were significantly higher in fat-type broiler lines than in their lean counterparts. 3. Developmental expression patterns of CIDEa and CIDEc mRNA were analysed in different tissue types (WAT, liver and kidney) in Arbor Acres broiler chickens, and CIDEa and CIDEc mRNA expression levels increased during sequential developmental stages, achieving peak expression levels at week 6. 4. These observations suggest that the functions of CIDEa and CIDEc reflect inherent characteristics of lipid metabolism that contribute to the differences in fat deposition between strains. The results in this study contribute to a more robust understanding of the tissue distribution and expression patterns of CIDEa and CIDEc mRNA and facilitate further research concerning the molecular mechanism underlying fat deposition in broiler chickens.

GENOME-WIDE MAPPING OF COPY NUMBER VARIATIONS IN COMMERCIAL HYBRID PIGS USING A HIGH-DENSITY SNP GENOTYPING ARRAY.

Copy number variations (CNVs) are important forms of structural variation in human and animals and can be considered as a major genetic component of phenotypic diversity. Here we used the Illumina PorcineSNP60 BeadChip V2 and a DLY [Duroc x (Large White x Landrace)] commercial hybrid population to identify 272 CNVs belonging to 165 CNV regions (CNVRs), of which 66 are new. As CNVRs are specific to origin of population, our DLY-specific data is an important complementary to the existing CNV map in the pig genome. Eight CNVRs were selected. for validation by quantitative real-time PCR (qRT-PCR) and the accurate rate was high (87.25%). Gene function analysis suggested that a common CNVR may play an important role in multiple traits, including growth rate and carcass quality.

Cloning and characterization of a benzoic acid/salicylic acid carboxyl methyltransferase gene involved in floral scent production from lily (Lilium 'Yelloween').

In lily flowers, the volatile ester methyl benzoate is one of the major and abundant floral scent compounds; however, knowledge regarding the biosynthesis of methyl benzoate remains unknown for Lilium. In this study, we isolated a benzoic acid/salicylic acid carboxyl methyltransferase (BSMT) gene, LiBSMT, from petals of Lilium 'Yelloween'. The gene has an open reading frame of 1083 base pairs (bp) and encodes a protein of 41.05 kDa. Sequence alignment and phylogenetic analyses of LiBSMT revealed 40-50% similarity with other known benzenoid carboxyl methyltransferases in other plant species, and revealed homology to BSMT of Oryza sativa. Heterologous expression of this gene in Escherichia coli yielded an enzyme responsible for catalyzing benzoic acid and salicylic acid to methyl benzoate and methyl salicylate, respectively. Quantitative real-time polymerase chain reaction analysis showed that LiBSMT was preferentially expressed in petals. Moreover, the expression of LiBSMT in petals was developmentally regulated. These expression patterns correlate well with the emission of methyl benzoate. Our results indicate that LiBSMT plays an important role in floral scent methyl benzoate production and emission in lily flowers.

Effect of surgery treatment on hypersplenism caused by cirrhotic portal hypertension.

AIM: Aim of the study was to summarize the types and quantities of peripheral hematocytopenia in the patients of hypersplenism caused by cirrhotic portal hypertension and investigate the effect of surgery, including splenectomy on the patient's peripheral blood cells and liver function. METHODS: The quantities of peripheral blood cells in the 322 patients of hypersplenism, caused by cirrhotic portal hypertension, were retrospectively studied. Then, the preoperative and postoperative values of peripheral blood cells and liver function were compared in 266 patients who were followed up. The liver function was scored and graded according to Child-Pugh scoring system. RESULTS: The study enrolled 322 patients who showed hematocytopenia, including multi-hemocyte decrease in 206 patients (64%) and simple hemocyte decrease in 116 patients (36%). After surgical treatment in the 226 patients who were followed up, the quantities of peripheral blood cells significantly increased (P<0.01), Child-Pugh grade A increased by 32 patients (14.2%), while Child-Pugh grade C increased only by 2 patients (0.9%), the liver function scores decreased (P<0.05). CONCLUSION: Hypersplenism caused by cirrhotic portal hypertension mainly manifests as a multi-hemocyte decrease and rarely shows single types of hematocytopenia. Surgical intervention including splenectomy can increase the reduction of hemocytes and promote the recovery of liver function.

Deletion of estrogen receptor beta accelerates early stage of bone healing in a mouse osteotomy model.

UNLABELLED: This study examined the role of estrogen receptor (ER) beta during mouse femoral fracture healing by employing ER knockout (KO) mice. The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification. INTRODUCTION: This study was conducted to examine the role of ER beta during fracture healing. METHODS: Female ERbeta knockout (KO) mice (18 weeks old) and age-matched female wild-type (WT) mice underwent open osteotomy on the right femur. They were sacrificed at 1, 2, 4 and 6 weeks post-fracture. The sera and callus samples were subjected to the following analyses: micro-computed tomography (CT)-based angiography, micro-CT evaluation, histological examination, histomorphometry examination, real-time polymerase chain reaction (PCR) analysis, biochemical marker, and mechanical testing. RESULTS: Micro-CT-based angiography showed that the total vessel volume at the fracture site was larger in the KO group than the WT group at 1 and 2 weeks post-fracture. Micro-CT analysis revealed that the callus volume was significantly higher in the KO group from week 2 to week 4 post-fracture when compared with the WT group consistent with the histological data. Analysis of biochemical markers indicated that circulating P1NP levels in the KO mice were significantly higher than in the WT mice from week 2 to week 4 and that temporal expression of circulating C-terminal telopeptide of type I collagen (CTX) levels was also higher in the KO mice than in the WT mice. These results were consistent with quantitative real-time PCR analysis. The ultimate load, stiffness, and energy to failure were significantly higher in the KO mice than in the WT mice at week 4. CONCLUSIONS: The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification, but not by the end of healing. Blockade of ERbeta can be considered as another therapeutic strategy for osteoporotic fracture and non-union fracture.

[Clinical report of hoding cricoarytenoid joint reduction with visual laryngoscope under intravenous anesthesia].

Objective: To investigate the reduction effect of hoding cricoarytenoid joint reduction with visual laryngoscope under intravenous anesthesia. Methods: The therapeutic effects of 40 patients with arytenoid dislocation(AD)treated by closed reduction in the single center from January 2020 to September 2021 were retrospectively analyzed, including 21 males and 19 females, median age 48 years. The etiology, symptoms, preoperative evaluation methods, reduction mode, reduction times, and the recovery of arytenoid cartilage movement and sound after reduction were evaluated and analyzed. Results: All patients had obvious hoarseness and breath sound before treatment. Under stroboscopic laryngoscope or electronic nasopharyngoscope, different degrees of vocal cord movement disorder and poor glottic closure can be seen. There were 28 cases of left dislocation, 9 cases of right dislocation and 3 cases of bilateral dislocation. The etiology of dislocation of cricoarytenoid joint: 25 cases (62.5%) of tracheal intubation under general anesthesia were the most common causes, was as follows by laryngeal trauma, gastroscopy, cough, vomiting and so on. Among them, 28 cases of reduction were initially diagnosed in our department, and 12 cases were diagnosed later after failure of reduction treatment. Of the 40 patients, 6 underwent reduction 24 hours after dislocation; 18 cases from 3 days to 1 month; 7 cases from 1 to 3 months; 6 cases were reset in 3~6 months; Over 6 months in 3 cases. After one reduction, 10 cases (10/40, 25%) recovered normal pronunciation, 14 cases (14/40, 35%) recovered normal pronunciation after two reduction, 10 cases (10/40, 25%) recovered normal pronunciation after three times, 2 cases (2/40, 5%) recovered normal pronunciation after four times, and 1 case (2.5%) recovered normal pronunciation after five times. Thin slice CT scan of larynx and cricoarytenoid joint reconstruction showed the types of AD: subluxation in 37 cases (92.5%) and total dislocation in 3 cases; 28 cases of left dislocation, 9 cases of right dislocation and 3 cases of bilateral dislocation; 29 cases (72.5%) had posterior dislocation and 11 cases (27.5%) had anterior dislocation. All patients were treated by intravenous anesthesia with arytenoid cartilage clamped by cricoarytenoid joint reduction forceps under visual laryngoscope. The curative effect was evaluated by stroboscopic laryngoscope and/or voice analysis at 1-2 weeks after operation. The vocal cord movement returned to normal and the pronunciation was good in 37 cases (92.5%). Conclusions: Hoding cricoarytenoid joint reduction with the vision laryngoscope under intravenous anesthesia is easy to operate and the reduction effect is more stable. It is a effective method for AD.

HCCS1 inhibits the stemness of human pancreatic cancer stem-like cells.

OBJECTIVE: SW1990-spheroid enrichment (SW1990-SE) cells were isolated using a new type of consecutive spheroid enrichment in this study. Cell surface markers were determined by flow cytometry for identification. In vivo tumorigenicity was applied by subcutaneous transplantation in nude mice for verifying the stemness characteristics of SW1990-SE cells. MATERIALS AND METHODS: SW1990-SE cells were subjected to lentivirus infection for establishing the SW1990-SE cell line stably low-expressing HCCS1 (SW1990-SE-shHCCS1) and negative control cell line (SW1990-SE-LV3NC). The stemness regulatory effects of HCCS1 on SW1990-SE cells were evaluated by cell counting kit-8 (CCK-8) assay and 96-wells plate single cell cloning assay in vitro. Subcutaneous transplantation in nude mice was conducted for evaluating the in vivo stemness regulation of HCCS1 on SW1990-SE cells.. RESULTS: HCCS1 knockdown in SW1990-SE cells did not markedly change the cell proliferation and doubling time, whereas the in vitro spheroid diameter and single cell cloning efficacy remarkably increased. In vivo experiments showed that HCCS1 knockdown greatly enhanced the tumorigenicity of SW1990-SE cells in nude mice. CONCLUSIONS: This study first obtains the human pancreatic cancer stem-like cells SW1990-SE through consecutive spheroid enrichment. Both in vivo and in vitro experiments verified that HCCS1 knockdown largely enhanced the stemness of SW1990-SE cells. Our study provides an important reference for the research of tumor stem cells.

Biocompatibility and membrane strength of C3H10T1/2 cell-loaded alginate-based microcapsules.

BACKGROUND: C3H10T1/2 cells, from a mouse embryonic fibroblast cell line, were used to investigate the improvement of alginate-based microencapsulated cells for cellular therapy. METHODS: Purified sodium alginate (PSA) and non-purified sodium alginate (SA) were used to prepare alginate-based microcapsules, and their biocompatibility and membrane strength were then compared for the purposes of analyzing the advantages of purifying SA. In addition, poly-l-lysine (PLL) was replaced by chitosan for alginate-chitosan microcapsule preparation. The process of optimization and chemical modification of alginate-chitosan microcapsules using polyethylene glycol was also reviewed. RESULTS: The results showed improved biocompatibility and membrane strength of PSA-based microcapsules. Under optimal conditions, mesenchymal stromal cell (MSC)-loaded alginate-chitosan microcapsules with good morphology could be obtained using PSA and chitosans of medium molecular weight (1.0-2.5 x 10(5)). A chitosan solution of 0.1% (w/v) and a reaction time of 7 min between alginate and chitosan were determined as optimal preparation parameters. DISCUSSION: It could be concluded that the chemical modification of alginate-based microcapsules can improve their biocompatibility.

[Pharyngeal space carcinoma ex pleomorphic adenoma：a case report].

Carcinoma ex pleomorphic adenoma is an epithelial malignant tumor of pleomorphic adenoma. This may be due to the accumulation of genetic instability caused by long-term pleomorphic adenomas. There are few reports of parapharyngeal space carcinoma ex pleomorphic adenoma in the literature study both at home and abroad. This article retrospectively summarized the clinical data of 1 case of pharyngeal space carcinoma ex pleomorphic adenoma and reviewed the literature. We strengthened the understanding of parapharyngeal space carcinoma ex pleomorphic adenoma, improve the accuracy of diagnosis and reduce misdiagnosis and mistreatment.