[Application and clinical significance of intercellular proximity labeling technique in chronic myelogenous leukemia].

Objective: This study aimed to explore the application of interaction-dependent fucosyl-biotinylation (FucoID), a chemical biology-based proximity labeling technique, in capturing tumor antigen-specific T cells and its clinical value in chronic myelogenous leukemia (CML) . Methods: Flow cytometry and fluorescence microscopy were employed to evaluate the experimental parameters for FucoID in CML. Peripheral blood samples were obtained from 14 newly diagnosed CML patients in the chronic phase. These samples underwent flow cytometry-based sorting and were subsequently labeled with FucoID to facilitate the isolation of tumor cells and T cells, followed by the immunophenotypic identification of tumor antigen-specific T cells. Finally, the diagnostic and therapeutic potential of FucoID in CML was assessed. Results: Initially, the experimental parameters for FucoID in CML were established. The proportion of CD3(+) T cells in patients was (8.96±6.47) %, exhibiting a marked decrease compared with that in healthy individuals at (38.89±22.62) %. The proportion of tumor-specific antigen-reactive T cells was (3.34±4.49) %, which demonstrated interpatient variability. In addition, the proportion of tumor-specific antigen-active T cells in CD4(+) T cells was (3.95±1.72) %, which was generally lower than the proportion in CD8(+) T cells at (5.68±2.18) %. Compared with those in tumor-specific antigen-nonreactive T cells, CCR7(-)CD45RA(-) effector memory T cells and CCR7(-)CD45RA(+) effector T cells were highly enriched in tumor-specific antigen-reactive T cells. Moreover, the intensity of tumor immune reactivity in patients exhibited a significant correlation with white blood cell count (WBC) and hemoglobin (HGB) levels in peripheral blood, while no such correlation was observed with other clinical baseline characteristics. Conclusion: The combination of FucoID and flow cytometry enables the rapid identification and isolation of tumor antigen-specific T cells in CML. The successful application of this method in CML and the implications of our findings suggest its potential clinical value in the field of hematologic malignancies.

[Rate and characteristics of H-type hypertension in Chinese hypertensive population and comparison with American population].

OBJECTIVE: To study the rate and characteristics of H-type hypertension in Chinese hypertensive population, and to compare them with the relevant data from the United States. METHODS: Observational studies on the prevalence of H-type hypertension in Chinese population published before April 30, 2022 were searched in several Chinese and English databases (PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Databases, and Chinese Biome-dical Literature Database). Study selection, date extraction and quality evaluation were conducted. Random effect model was used to estimate the rate of H-type hypertension in hypertensive patients and the pooled prevalence of H-type hypertension. Stratified analysis was used to explore the distribution characteristics of H-type hypertension in China. We made meta-regression to search the source of heterogeneity. The National Health and Nutrition Examination Survey (NHANES) population from 1999 to 2006 in the United States was divided into four stages according to the time of data collection. Basic information of the participants was acquired from the database and the rate and prevalence of H-type hypertension analyzed. RESULTS: This study was finally comprised of 33 studies, involving 78 470 patients with hypertension, among whom 59 842 patients were with H-type hypertension. The rate of H-type hypertension in hypertensive population in China was 73.1% (95%CI: 69.3%-76.9%, I2=99.4%, P < 0.001), and the prevalence of H-type hypertension in general population was 26.9% (95%CI: 21.1%-32.8%, I2=99.8%, P < 0.001). In the stratified analysis, the rate of H-type hypertension was higher among the elderly over 65 years, males, ethnic minorities, and residents in the inland, western, northern, and rural areas. During the decade from 2011 to 2020, the rate of H-type hypertension in China declined slowly (2011-2013: 79.2% vs. 2014-2016: 70.4% vs. 2017-2020: 66.6%, P < 0.001). Meta-regression showed that area was the source of heterogeneity. The rate of H-type hypertension in the United States increased over time, reaching a high value in 2003-2004 and then declining in 2005-2006. The rate of H-type hypertension in hypertensive patients and the prevalence of H-type hypertension in general population in the United States was lower than that in China. CONCLUSION: Although the rate of H-type hypertension in Chinese hypertensive patients has a downtrend, it still far exceeds that in the United States, especially in the elderly, males, ethnic minorities, and residents in the inland, western, northern, and rural areas. Understanding the epidemiology of H-type hypertension provides scientific evidence for further prevention of cardiovascular and cerebrovascular diseases.

[Value of indocyanine green fluorescence tracer in laparoscopic cholecystectomy for acute cholecystitis].

Objective: To explore the value of low-dose indocyanine green (ICG) fluorescence imaging in laparoscopic cholecystectomy (LC) for acute cholecystitis. Methods: Clinical data of 198 patients with acute cholecystitis and had received LC in Changzhou No.2 People's Hospital from January 2020 to September 2021 were collected. In the fluorescence group (n=97), peripheral intravenous injection of ICG was performed 15 minutes before LC, while conventional white light was applied in the control group (n=101). The efficiency of bile duct discrimination, operation time, intraoperative bleeding and postoperative complications were compared between the two groups. Results: Of the 198 patients, 86 were males and 112 females. The differences were not statisticly significant in age [52 (44, 63) vs 56 (46, 68) years, P>0.05], history of chronic inflammation [34(35.1%) vs 31(30.7%) cases, P>0.05] and other clinical baseline data between the two groups. Compared with the control group, the fluorescence group had higher efficiency of bile duct identification [18 (16,19) vs 38 (28,55) min,P<0.001], shorter operation time [45 (40,60) vs 80 (65,100) min,P<0.001], less intraoperative bleeding [10 (5,15) vs 60 (20,100) ml,P<0.001], and less postoperative liver function damage [alanine aminotransferase 35.0 (23.4,51.0) vs 98.3 (67.0,134.8)U/L,P<0.001]. In the control group, there was one case of biliary duct injury during operation, one case of postoperative biliary fistula, and one case of postoperative hemorrhage. No similar adverse event was found in fluorescence group. Conclusions: ICG fluorescence imaging can improve the efficiency of LC for patients with acute cholecystitis. It is easy to operate and has a good clinical application value.

[Clinical analysis of 555 outpatients with hand, foot and mouth diseases caused by different enteroviruses].

Objective: To study the clinical characteristics of outpatients with hand, foot and mouth disease (HFMD) caused by different serotypes of enteroviruses. Methods: This was a prospective study. From February 2017 to March 2018, 563 outpatients with HFMD were enrolled by systematic sampling in the Department of Infectious Diseases, Henan Children's Hospital. Throat swabs were collected to determine the serotypes via PCR. Demographic, clinical, and laboratory data were collected by standard questionnaire. All cases were followed up twice at 2 and 9 weeks after the initial outpatient visit through telephone interview. A total of 563 cases were enrolled and 555 (98.6%) cases were positive for human enteroviruses, including 338 (60.9%) males. Analyses were stratified by enterovirus serotypes, Chi square test or Fisher's exact test, Rank sum test was used for comparison among different groups. Results: The age of 555 cases was 24.2 (16.4, 41.3) months. Among them 44.0% (224 cases) were identified as coxsackievirus (CV)-A6, while 189 cases, 35 cases, 14 cases and 73 cases were identified as CV-A16, enterovirus (EV)-A71, CV-A10 and other serotypes, respectively. Fever (≥37.5 ℃) was present in 51.4% (285/555) of laboratory confirmed cases. The proportions of fever in cases of CV-A6 (68.9%(168/244)) and CV-A10 (12/14) were significantly higher than those in cases of CV-A16 (31.7%(60/189),χ(2)=57.344,14.313,both P=0.000), other serotypes (43.8%(32/73),χ(2)=15.101 and 8.242, P=0.000 and 0.004) and EV-A71 (37.1%(13/35), χ(2)=13.506 and 9.441, P=0.000 and 0.002) respectively. There was no significant difference between CV-A6 and CV-A10 in presentation of fever (χ(2)=1.785, P=0.182). There were 359 cases (64.7%) with eruptions in mouth, hands, feet and buttocks. Cases infected with EV-A71 had the highest proportions (74.3%(26/35)) of rash emerging simultaneously in mouth, hands, feet, and buttocks. The proportion in cases of CV-A16, CV-A6, CVA10 and other serotype were 73.5% (139/189), 61.9% (151/244), 7/14 and 49.3% (36/73), respectively. The proportion of rash on other parts of body, such as face, limbs or torso in cases infected with CV-A6 (16.8% (41/244)) was the higherest and the proportion in cases of CV-A16, EV-A71, CV-A10 or other serotypes were 8.5% (16/189) , 5.7% (2/35) , 1/14, 6.8% (5/73) , respectively. None of these cases developed serious complications. Desquamation occurred in 45.5% (179/393) cases 7.5 (5.0, 9.0) days after disease onset and 13.5% (53/393) cases showed onychomadesis 31.0 (18.0, 33.5) days after disease onset. The proportion of desquamation and onychomadesis associated with CV-A6 (64.2% (95/148) and 31.8% (47/148)) was significantly higher than CV-A16 (31.8% (49/154) and 1.3% (2/154), χ(2)=33.601 and 52.482, both P=0.000) and other serotypes (38.0%(19/50) and 6.0%(3/50),χ(2)=10.236 and 12.988, P=0.001 and 0.000). Desquamation appeared more in cases of CV-A6 than in cases of CV-A10 (2/11,χ(2)=9.386, P=0.002), with the proportion of onychomadesis higher in CV-A6 than in EV-A71 (3.3% (1/30),χ(2)=11.088, P=0.001). Conclusion: Clinical manifestation such as fever, rash emerging parts, desquamation and onychomadesis are different among outpatient HFMD cases infected with CV-A16, CV-A6, EV-A71, CV-A10 and other enteroviruses.

Long noncoding RNA GIHCG is a potential diagnostic and prognostic biomarker and therapeutic target for renal cell carcinoma.

OBJECTIVE: Long noncoding RNA (lncRNA) GIHCG has been reported as an oncogene in hepatocellular carcinoma. However, the expression, roles, and clinical values of GIHCG in renal cell carcinoma (RCC) remain unclear. The aim of this study was to investigate the expression, roles, diagnostic and prognostic values of GIHCG in RCC. PATIENTS AND METHODS: The expression of GIHCG in 46 pairs of RCC tissues and adjacent normal renal tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). GIHCG serum level in 46 RCC patients, 46 age- and sex-matched healthy controls, 20 pre- and post-surgery RCC patients was measured by qRT-PCR. The diagnostic values of serum GIHCG were evaluated by receiver operating characteristic (ROC) curves analysis. The effect of GIHCG on RCC cell proliferation was evaluated using Cell Count Kit-8 assay, and the effect of GIHCG on RCC cell migration was evaluated using transwell migration assay. RESULTS: GIHCG is upregulated in RCC tissues compared with adjacent normal renal tissues. Increased expression of GIHCG is positively correlated with advanced TNM stages, Fuhrman grades, and poor prognosis. Serum GIHCG level is also significantly upregulated in RCC patients and correlated with advanced TNM stages. Serum GIHCG could accurately discriminate RCC patients from healthy controls, and also early stage RCC patients from healthy controls. Furthermore, serum GIHCG level is positively correlated with GIHCG expression in RCC tissues. Serum GIHCG level is significantly reduced after radical resection of RCC. Functional assays showed that knockdown of GIHCG significantly represses proliferation and migration of RCC cells. CONCLUSIONS: Long noncoding RNA GIHCG would sever as a novel diagnostic and prognostic biomarker and therapeutic target for RCC.

Biological and ecological evidences suggest Stipa krylovii (Pooideae), contributes to optimal growth performance and population distribution of the grasshopper Oedaleus asiaticus.

Oedaleus asiaticus Bey. Bienko is a significant grasshopper pest species occurring in north Asian grasslands. Outbreaks often result in significant loss in grasses and economic losses. Interestingly, we found this grasshopper was mainly restricted to Stipa-dominated grassland. We suspected this may be related to the dominant grasses species, Stipa krylovii Roshev, and hypothesized that S. krylovii contributes to optimal growth performance and population distribution of O. asiaticus. A 4 year investigation showed that O. asiaticus density was positively correlated to the above-ground biomass of S. krylovii and O. asiaticus growth performance variables (survival rate, size, growth rate) were significantly higher in Stipa-dominated grassland. A feeding trial also showed that O. asiaticus had a higher growth performance when feeding exclusively on S. krylovii. In addition, the choice, consumption and the efficiency of conversion of ingested food (ECI) by O. asiaticus was highest for S. krylovii compared with other plant species found in the Asian grasslands. These ecological and biological traits revealed why O. asiaticus is strongly associated with Stipa-dominated grasslands. We concluded that the existence of S. krylovii benefited the growth performance and explained the distribution of O. asiaticus. These results are useful for improved pest management strategies and developing guidelines for the monitoring of grasshopper population dynamics against the background of vegetation succession and changing plant communities in response to activities such as grazing, fire and climate change.

Valproate promotes survival of retinal ganglion cells in a rat model of optic nerve crush.

Valproate (VPA) is an anticonvulsant and mood-stabilizing drug. It is a broad-spectrum histone deacetylase inhibitor with neuroprotective effects. We investigated whether VPA reduces retinal neuronal death induced by optic nerve crush (ONC). To evaluate further VPA-mediated neuroprotection on retinal ganglion cells (RGCs), another histone deacetylase (HDAC) inhibitor, sodium butyrate (SB) was compared with VPA. Adult male Wistar rats were subjected to ONC injury. VPA and SB were administered subcutaneously 1 day prior to ONC until sacrifice 14 days later. RGC density was counted using hematoxylin and eosin (H&E) staining of the retinal section and retrograde labeling with FluoroGold. Retinal function was evaluated by electroretinography (ERG) after ONC. Immunofluorescence of activated caspase-3 in ganglion cell layer (GCL) and the detection of bcl-2 mRNA expression in the retina were used to evaluate apoptosis of retinal cells. In addition, brain-derived neurotrophic factor (BDNF) in retinas was measured using an enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Western blot was used to analyze histone H3 acetylation, the protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) phosphorylation levels, and tropomyosin-related kinase B (TrkB) levels. The transcriptional activation of the BDNF gene was analyzed by measuring the levels of acetylation or methylation of histone H3 using chromatin immunoprecipitation assay. The RGC density in the VPA and SB treated-groups were significantly higher as compared with those of the corresponding vehicle group following ONC. VPA and SB suppressed reductions in a- and b-wave amplitudes of the ERG and attenuated the activation of caspase-3 in the RGCs, which was accompanied by upregulation in Akt and Erk phosphorylation in the retina. Furthermore, VPA upregulated levels of bcl-2, BDNF, TrkB in the retina post-injury. VPA and SB treatment resulted in the hyperacetylation of histone H3K14, attenuated histone H3K9 hypermethylation in the BDNF promoter, and promoted transcriptional activity. These results demonstrate that VPA appears to protect RGCs from ONC by inhibiting neuronal apoptosis possibly via the activation of BDNF-TrkB signaling and HDAC inhibition.

A protective role for programmed death 1 in progression of murine adriamycin nephropathy.

Programmed death 1 (PD-1) is a novel member of the CD28/cytotoxic T-lymphocyte-associated protein-4 superfamily, which plays an important role in the regulation of activated T cells. However, it is not clear how PD-1 is expressed in normal and diseased kidney, nor if it has a role in progression of chronic renal disease. PD-1 expression and the effect of monoclonal anti-PD-1 antibody (Ab) were examined in murine adriamycin nephropathy (AN). BALB/c mice were divided into three groups: (a) normal mice, (b) adriamycin (ADR) with control immunoglobulin (Ig)G (ADR-IgG), and (c) ADR with anti-PD-1 Ab (ADR-Ab). AN was induced by a single intravenous injection of ADR. Anti-PD-1 Ab was given by intraperitoneal injection on alternate days from day 0 to day 10, or to day 18. Animals were killed at week 4. Renal function, histological change, and cytokine expression were examined. PD-1 mRNA was detected in kidney tissue of mice with AN in a dose- and time-dependent manner. PD-1 was mainly expressed on injured tubule cells and some interstitial cells, which co-stained with alpha-smooth muscle actin in AN, but not in normal kidney. Anti-PD-1 treatment up to day 18, but not to day 10, worsened glomerular and tubulointerstitial injury. The ratio of urinary protein/creatinine was significantly higher in ADR-Ab mice than ADR-IgG mice. The number of macrophages was significantly increased in ADR-Ab mice compared with ADR-IgG mice. Blockade of PD-1 worsened progressive renal histopathological and functional injury in murine AN. This suggests a possible protective role for PD-1 in chronic renal disease, and its potential as a treatment to slow disease progression.