[Therapeutic effect of recombinant human growth hormone on children with growth hormone deficiency and different pituitary developmental conditions: a prospective study]. / é‡ç»„äººç”Ÿé•¿æ¿€ç´ æ²»ç–—ä¸åŒåž‚ä½“å‘è‚²çŠ¶å†µç”Ÿé•¿æ¿€ç´ ç¼ºä¹ç—‡æ‚£å„¿ç–—æ•ˆçš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS: In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.

The activation of GABAergic neurons in the hypothalamic tuberomammillary nucleus attenuates sevoflurane and propofol-induced anesthesia in mice.

Background: The histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) have been suggested to play a vital role in maintaining a rising state. But the neuronal types of the TMN are in debate and the role of GABAergic neurons remains unclear. Methods: In the present study, we examined the role of TMN GABAergic neurons in general anesthesia using chemogenetics and optogenetics strategies to regulate the activity of TMN GABAergic neurons. Results: The results indicated that either chemogenetic or optogenetic activation of TMN GABAergic neurons in mice decreased the effect of sevoflurane and propofol anesthesia. In contrast, inhibition of the TMN GABAergic neurons facilitates the sevoflurane anesthesia effect. Conclusion: Our results suggest that the activity of TMN GABAergic neurons produces an anti-anesthesia effect in loss of consciousness and analgesia.

CircPVT1 promotes ER-positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS.

The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and endocrine therapy resistance remain incompletely understood. Here, we report that circPVT1, a circular RNA generated from the lncRNA PVT1, is highly expressed in ERα-positive breast cancer cell lines and tumor samples and is functionally important in promoting ERα-positive breast tumorigenesis and endocrine therapy resistance. CircPVT1 acts as a competing endogenous RNA (ceRNA) to sponge miR-181a-2-3p, promoting the expression of ESR1 and downstream ERα-target genes and breast cancer cell growth. Furthermore, circPVT1 directly interacts with MAVS protein to disrupt the RIGI-MAVS complex formation, inhibiting type I interferon (IFN) signaling pathway and anti-tumor immunity. Anti-sense oligonucleotide (ASO)-targeting circPVT1 inhibits ERα-positive breast cancer cell and tumor growth, re-sensitizing tamoxifen-resistant ERα-positive breast cancer cells to tamoxifen treatment. Taken together, our data demonstrated that circPVT1 can work through both ceRNA and protein scaffolding mechanisms to promote cancer. Thus, circPVT1 may serve as a diagnostic biomarker and therapeutic target for ERα-positive breast cancer in the clinic.

Synaptosomal Actin Dynamics in the Developmental Visual Cortex Regulate Behavioral Visual Acuity in Rats.

Purpose: Synaptosomal actin dynamics are essential for synaptic structural stability. Whether actin dynamics are involved in structural and functional synaptic plasticity within the primary visual cortex (V1) or behavioral visual acuity in rats has still not been thoroughly investigated. Methods: Synaptosome preparation and western blot analysis were used to analyze synaptosomal actin dynamics. Transmission electron microscopy was used to detect synaptic density and mitochondrial area alterations. A visual water maze task was applied to assess behavioral visual acuity. Microinjection of the actin polymerization inhibitor or stabilizer detected the effect of actin dynamics on visual function. Results: Actin dynamics, the mitochondrial area, and synaptic density within the area of V1 are increased during the critical period for the development of binocularity. Microinjection of the actin polymerization inhibitor cytochalasin D into the V1 decreased the mitochondrial area, synaptic density, and behavioral visual acuity. Long-term monocular deprivation reduced actin dynamics, the mitochondrial area, and synaptic density within the V1 contralateral to the deprived eye compared with those ipsilateral to the deprived eye and impaired visual acuity in the amblyopic eye. In addition, the mitochondrial area, synaptic density, and behavioral visual acuity were improved by stabilization of actin polymerization by jasplakinolide microinjection. Conclusions: During the critical period of visual development of binocularity, synaptosomal actin dynamics regulate synaptic structure and function and play roles in behavioral visual acuity in rats.

Nuclear translocation of ATG5 induces DNA mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) via interacting with Mis18α in colorectal cancer.

BACKGROUND AND PURPOSE: It is well known that microsatellite instability-high (MSI-H) is associated with 5-fluorouracil (5-FU) resistance in colorectal cancer. MSI-H is the phenotype of DNA mismatch repair deficiency (MMR-D), mainly occurring due to hypermethylation of MLH1 promoter CpG island. However, the mechanisms of MMR-D/MSI-H are unclear. We aim to investigate the pathway of MMR-D/MSI-H involved in 5-FU resistance. EXPERIMENTAL APPROACH: Human colorectal cancer specimens were diagnosed for MSI-H by immunohistochemistry and western blotting. Proteome microarray interactome assay was performed to screen nuclear proteins interacting with ATG5. Nuclear ATG5 and ATG5-Mis18α overexpression were analysed in ATG5high colorectal cancer bearing mice. The methylation assay determined the hypermethylation of hMLH1 promoter CpG island in freshly isolated human colorectal cancer tissue samples and HT29atg5 and SW480atg5 cancer cells. KEY RESULTS: In ATG5high colorectal cancer patients, 5-FU-based therapy resulted in nuclear translocation of ATG5, leading to MSI-H. Colorectal cancer in Atg5 Tg mice demonstrated 5-FU resistance, compared to Atg5+/- and WT mice. Proteome microarray assay identified Mis18α, a protein localized on the centromere and a source for methylation of the underlying chromatin, which responded to the translocated nuclear ATG5 leading to ATG5-Mis18α conjugate overexpression. This resulted in MLH1 deficiency due to hypermethylation of hMLH1 promoter CpG island, while the deletion of nuclear Mis18α failed to induce ATG5-Mis18α complex and MMR-D/MSI-H. CONCLUSIONS AND IMPLICATIONS: Nuclear ATG5 resulted in MMR-D/MSI-H through its interaction with Mis18α in ATG5high colorectal cancer cells. We suggest that ATG5-Mis18α or Mis18α may be a therapeutic target for treating colorectal cancer.

Estrogen-induced circRNA, circPGR, functions as a ceRNA to promote estrogen receptor-positive breast cancer cell growth by regulating cell cycle-related genes.

Estrogen and estrogen receptor (ER)-regulated gene transcriptional events have been well known to be involved in ER-positive breast carcinogenesis. Meanwhile, circular RNAs (circRNAs) are emerging as a new family of functional non-coding RNAs (ncRNAs) with implications in a variety of pathological processes, such as cancer. However, the estrogen-regulated circRNA program and the function of such program remain uncharacterized. Methods: CircRNA sequencing (circRNA-seq) was performed to identify circRNAs induced by estrogen, and cell proliferation, colony formation, wound healing, transwell and tumor xenograft experiments were applied to examine the function of estrogen-induced circRNA, circPGR. RNA sequencing (RNA-seq) and ceRNA network analysis wereperformed to identify circPGR's target genes and the microRNA (miRNA) bound to circPGR. Anti-sense oligonucleotide (ASO) was used to assess circPGR's effects on ER-positive breast cancer cell growth. Results: Genome-wide circRNA profiling by circRNA sequencing (circRNA-seq) revealed that a large number of circRNAs were induced by estrogen, and further functional screening for the several circRNAs originated from PGR revealed that one of them, which we named as circPGR, was required for ER-positive breast cancer cell growth and tumorigenesis. CircPGR was found to be localized in the cytosol of cells and functioned as a competing endogenous RNA (ceRNA) to sponge miR-301a-5p to regulate the expression of multiple cell cycle genes. The clinical relevance of circPGR was underscored by its high and specific expression in ER-positive breast cancer cell lines and clinical breast cancer tissue samples. Accordingly, anti-sense oligonucleotide (ASO) targeting circPGR was proven to be effective in suppressing ER-positive breast cancer cell growth. Conclusions: These findings reveled that, besides the well-known messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA) and enhancer RNA (eRNA) programs, estrogen also induced a circRNA program, and exemplified by circPGR, these estrogen-induced circRNAs were required for ER-positive breast cancer cell growth, providing a new class of therapeutic targets for ER-positive breast cancer.

Prevention of Diabetes in Overweight/Obese Adults through Traditional Chinese Patent Medicine: Study Protocol for a Prospective Cohort Study.

Background. Early intervention in prediabetes can prevent or delay the incidence of type 2 diabetes mellitus (T2DM). Traditional Chinese patent medicine (TCPM) is widely used in China to prevent T2DM. This study aims to evaluate the efficacy and safety of TCPMs for preventing T2DM. Method/Design. This study is a multicenter, cohort study with two arms. A total of 600 participants will be recruited. The participants will be divided into either intervention or control groups according to their own desire, and the exposure factor is the application of TCPMs. All participants will be encouraged to lead a healthy lifestyle, and the intervention group also used TCPMs based on syndrome differentiation. Incident diabetes and normalization of blood glucose are indexes of end point. Safety assessments and adverse event monitoring will also be conducted. The treatment duration is set for 24 weeks, and we will follow-up for another 2 years. Discussion. This trial may provide initial evidence regarding the efficacy and safety of TCPMs plus lifestyle intervention (LI) compared to LI alone for preventing T2DM and provide a comprehensive intervention plans that choose suitable TCPMs for diabetes prevention according to syndrome differentiation. Trial Registration Number. Chinese Clinical Trial Registry ID: ChiCTR1900023541, registered on 1 Jun 2019. The version identifier is 2018121702.

Protective Effects of Rocuronium Bromide on Ischemia-Reperfusion Injury in Skeletal Muscle Induced by Tourniquet in Patients Undergoing Elective Unilateral Total Knee Arthroplasty: A Prospective, Double Blind, Randomized, Controlled Study.

PURPOSE: To investigate the effects of different doses of rocuronium on ischemia-reperfusion injury in skeletal muscle induced by tourniquet in patients undergoing elective unilateral total knee arthroplasty. PATIENTS AND METHODS: A total of 90 patients undergoing elective unilateral knee arthroplasty under general anesthesia combined with femoral nerve block were randomly divided into 3 groups: normal saline group (group S), rocuronium 0.6 mg/kg group (group L), and rocuronium 1.2 mg/kg group (group H). The primary outcome was the expression of dystrophin in skeletal muscle at 60 min after ischemia. Secondary outcomes included the concentration of malondialdehyde (MDA) and neuronal nitric oxide synthase (nNOS) in blood at 5 min and 30 min after reperfusion. In addition, thigh girth at 24 h and 48 h after operation, the leaving bed time, the incidence of tourniquet-related hypertension and short-term (3 days after operation) complications (nausea and vomiting, swelling, blister, wound infection) and long-term (3 months after operation) complications (joint instability, stiffness, nerve paralysis, pain) were recorded. MAIN RESULTS: The expression of dystrophin in the rocuronium group was higher than that in group S after ischemia (P <0.05). The concentration of MDA in the rocuronium 1.2 mg/kg group was lower at 30 min after reperfusion (P < 0.05). There was no significant difference in nNOS among groups at each time point (P > 0.05). The change of thigh girth was the smallest in the rocuronium 1.2 mg/kg group after operation (P<0.05). The leaving bed time was significantly earlier after operation in the rocuronium group than that in group S (P <0.05). CONCLUSION: Rocuronium can protect skeletal muscle from ischemia-reperfusion injury induced by tourniquet. The mechanism may be related to the fact that rocuronium can reduce the loss of dystrophin in skeletal muscle and have the effects of anti-oxidation and anti-stress. TRIAL REGISTRATION: The study was registered at http://www.chictr.org.cn (ChiCTR1800019221, registered on 2018-10-31).

Different patterns of changes between actin dynamics and synaptic density in the rat's primary visual cortex during a special period of visual development.

In our previous study, we found that the normalized levels of the synaptosomal filament actin (F-actin) to monomeric global actin (G-actin) ratio in the primary visual cortex (V1) of rats was significantly lower on postnatal day (P) 45 compared with P30, however, the synaptic density in the monocular area of primary visual cortex (V1M) maintained a stable high level from P30 to P45. The mechanisms underlying the different patterned of change in synaptic density and actin rearrangements from P30 to P45 are unclear. During visual development, there is a synaptic pruning process in the binocular segment of primates' visual cortex (V1B) and we suppose the pruning activity may contribute to the decreased synaptosomal F-actin to G-actin ratio. To address this issue, first, samples were derived from the region of V1B for TEM analysis but no significant difference was demonstrated between the P30 and P45 groups. In addition, the expression of PSD-95 detected by immunobloting in the synaptosomes of V1 at P30 and P45 also showed no significant difference. Combined with the previous results of actin dynamics in the V1 and synaptic density in the V1M, we conclude that the synaptic density and actin dynamics in the rats' primary visual cortex are inter-related but not absolutely identical. This study suggests actin cytoskeleton not only provides the structural basis but also regulates a various array of cellular activities underlying synaptic function. Besides, it highlights a further research of synaptic pruning.

Effects of intraoperative dexmedetomidine with intravenous anesthesia on postoperative emergence agitation/delirium in pediatric patients undergoing tonsillectomy with or without adenoidectomy: A CONSORT-prospective, randomized, controlled clinical trial.

Postoperative emergence agitation/delirium (POED) is a common complication in pediatric surgery patients, which increases the risk of developing postoperative airway obstruction and respiratory depression. This study aims to investigate the safety and efficacy of intraoperative infusion of dexmedetomidine (DEX) and its effects on POED in pediatric patients undergoing tonsillectomy with or without adenoidectomy.Sixty patients scheduled for tonsillectomy with or without adenoidectomy, aged 2 to 8 years, were randomly allocated into 2 groups (n = 30). Pediatric patients in the group DEX received intravenous (IV) DEX 1 µg/kg over 10 minutes, followed by 0.5 µg/kg/h continuous infusion, and the same volume of 0.9% saline was administrated in the group control. Anesthesia was maintained with target-controlled infusion (TCI) of propofol and remifentanyl. Intraoperative heart rate (HR), noninvasive blood pressure (NIBP), blood oxygen saturation (SPO2), recovery time, and extubation time were recorded. Pain level was evaluated using the objective pain score (OPS), pediatric anesthesia emergence delirium (PAED) scale and Cole 5-point scale (CPS) was used to evaluate POED when patients at 0, 5, 15 minutes, and then at intervals of 15 minutes for 60 minutes after parents arrival at postanesthesia care unit (PACU).The results showed that intraoperative HR was significantly lower in group DEX (P <0.05), mean diastolic and systolic NIBP was not statistically different between groups. Time to wake and time to extubation were lengthened in group DEX as compared with group control (P <0.05). OPS and CPS were lower in group DEX at 15, 30, and 45 minutes time points (P <0.05); however, there were no significantly differences in the PAED score at different time points in the PACU.The present data suggested that intraoperative infusion of dexmedetomidine combined with intravenous anesthetics can provide satisfactory intraoperative conditions for pediatric patients undergoing tonsillectomy with or without adenoidectomy, without adverse hemodynamic effects, though the lower incidence of POED was not observed.

DNase I aggravates islet ß-cell apoptosis in type 2 diabetes.

Deoxyribonuclease I (DNase I) is an endonuclease responsible for the destruction of chromatin during apoptosis. However, its role in diabetes remains unclear. The aim of the current study was to investigate the role of DNase I combined with high glucose levels in ß­cell apoptosis. Human samples were collected and the DNase I activity was examined. High glucose­cultured INS­1 cells were transfected with DNase I small interfering RNA (siRNA) and the cell apoptosis was examined by western blotting and flow cytometry. Cell viability was analyzed by the Cell Counting Kit­8 assay. Cell apoptosis resulting from 50 mU/µl DNase I was also observed by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick­end labeling stain and western blotting. Compared with healthy controls, the serum DNase I activity of patients with diabetes was significantly increased (P<0.05). In addition, DNase I expression was observed to be significantly increased in human pancreatic tissues. The addition of high glucose upregulated the cell apoptotic rate, whereas DNase I knockdown significantly reduced apoptosis in cells treated with high glucose. In addition, the western blotting results indicated that caspase­3 was increased subsequent to treatment of cells with 30 mM high glucose, however, this increase can be reversed by transfection with DNase I siRNA (P<0.05). Compared with cells cultured in normal conditions and high glucose, 50 mU/µl DNase I was able to significantly increase the cell apoptotic rate and level of caspase-3. DNase I activity was observed to be increased in type 2 diabetes, and high glucose combined with increased DNase I is suggested to aggravate ß-cell apoptosis.

Clinical Outcomes of Wulingsan Subtraction Decoction Treatment of Postoperative Brain Edema and Fever as a Complication of Glioma Neurosurgery.

Objective. To evaluate the efficacy of Wulingsan subtraction ( WLSS) decoction in the treatment of postoperative brain edema and fever as a complication of glioma neurosurgery. Methods. This retrospective study was conducted at the Department of Neurosurgery of Liaocheng People's Hospital. Patients hospitalized between March 2011 and December 2014 were divided into three groups: Group A received WLSS oral liquid (50 mL), twice a day; Group B received an intravenous infusion of mannitol; and Group C received WLSS combined with mannitol (n = 30 patients per group). All patients were treated for 10 days continuously. Therapeutic efficacy was evaluated by measuring body temperature and indicators of renal function before and 3, 5, and 10 days after treatment. Results. Compared to the other two groups, significantly greater clinical efficacy was observed in the patients treated with mannitol (Group B; P < 0.05), although marked clinical efficacy was also observed over time in patients treated with WLSS (Group A). After 5 days, the quantifiable effects of the WLSS and mannitol combination group (Group C) were substantial (P < 0.05). The renal damage in Group B was more obvious after 5 days and 10 days. Conclusion. Compared with mannitol treatment alone, WLSS combined with mannitol induced a more rapid reduction in body temperature. Our findings suggest that patients should be started on mannitol for 3 days and then switched to WLSS to achieve obvious antipyretic effects and protect renal function. This method of treatment should be considered for clinical applications.

[Mechanism of Polypeptide Extract from Scorpion Venom Combined Rapamycin in Enhancing Autophagy of H22 Hepatoma Cells: an Experimental Study].

OBJECTIVE: To observe enhanced effects of polypeptide extract from scorpion venom (PESV) combined Rapamycin on autophagy of H22 hepatoma cells in mice and to explore its possible mechanism. METHODS: The H22 hepatocarcinoma cell suspension was subcutaneously inoculated into 40 Kunming mice. Then tumor-bearing mice were randomly divided into four groups, i.e., the control group,the high dose PESV group, the low dose PESV group, and the combination group (high dose PESV + Rapamycin), 10 in each group. Mice in high and dose PESV groups were administered with 20 mg/kg and 10 mg/kg PESV respectively by gastrogavage. Mice in the combination group were administered with 2 mg/kg rapamycin and 20 mg/kg PESV by gastrogavage. The intervention lasted for 14 successive days. The tumor volume was measured once every other day, the tumor growth curve was drawn, and then the tumor inhibitory rate calculated. Pathological changes of the tumor tissue were observed by HE staining. Protein expression levels of mammal target of rapamycin (mTOR), UNC-51-like kinase-1 (ULK1), microtubule-associated protein1 light chain3 (MAPILC3A), and Beclin1 were detected by immunohistochemical assay. RESULTS: The growth of H22 hepatoma transplantation tumor was inhibited in high and low dose PESV groups and the combination group (P < 0.05). And there was statistical difference in tumor weight and tumor volume between the combination group and high and low dose PESV groups (P < 0.05). There was no statistical difference in tumor weight or tumor volume between the high dose PESV group and the low dose PESV group (P > 0.05). lmmunohistochemical assay showed that the protein expression of mTOR was higher, but protein expressions of ULK1, MAP1LC3A, Beclin1 were lower in the control group than in the rest 3 groups (P < 0.05, P < 0.01). Compared with the high dose PESV group, protein expressions of ULK1, MAP1LC3A, and Beclin1 were obviously lower (P < 0.05). CONCLUSION: PESV combined Rapamycin might inhibit the development of H22 hepatoma transplantation tumor in mice possibly through inhibiting the activity of mTOR, enhancing expressions of ULK1, MAP1LC3A, and Beclin1.

Protective effect of L-carnitine in cyclophosphamide-induced germ cell apoptosis.

Cyclophosphamide (CP) is a widely used anti-cancer agent; however, it can also induce serious male infertility. There are currently no effective drugs to alleviate this side-effect. L-Carnitine has been used to treat male infertility, but whether it can be used to protect against CP-induced male infertility is still unclear. This study aims to explore the effect and mechanism of L-carnitine in male infertility induced by CP. CP was used to establish an animal model. After three weeks of treatment, rats were sacrificed and testis and serum were harvested for further evaluation. Testosterone and estrogen levels were measured by enzyme-linked immunosorbent assay (ELISA). Testicular injury was examined by hematoxylin and eosin (H & E) staining, and germ-cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of LC3 and Beclin-1 was examined by immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR), respectively. Compared with the CP group, L-carnitine significantly increases sperm motility, viability, and testosterone level (P<0.05). Western blot and real-time PCR results showed that L-carnitine treatment can significantly up-regulate the LC3-II and Beclin-1 expression in the CP+L-carnitine group when compared with the control group (P<0.05). In addition, TUNEL-positive cells were also more numerous in the CP group; however, L-carnitine can effectively retard cell apoptosis in the CP+L-carnitine group. In conclusion, L-carnitine contributes to the inhibition of cell apoptosis and the modulation of autophagy in protecting CP-induced testicular injury. These results suggest the applicability of L-carnitine in the treatment of male infertility.

Corneal curvature radius and associated factors in Chinese children: the Shandong Children Eye Study.

PURPOSE: To investigate the distribution of the (CCR) and its associated factors in children. METHODS: Using a random cluster sampling method, the school-based, cross-sectional Shandong Children Eye Study included children aged 4 to 18 years from the rural county of Guanxian and the city of Weihai in the province of Shandong in East China. CCR was measured by ocular biometry. RESULTS: CCR measurements were available for 5913 (92.9%) out of 6364 eligible children. Mean age was 10.0±3.3 years, and mean CCR was 7.84±0.27 mm (range: 6.98 to 9.35 mm). In multivariate linear regression analysis, longer CCR (i.e. flatter cornea) was significantly associated with the systemic parameters of male sex (P<0001; standardized regression coefficient beta: -0.08; regression coefficient B: -0.04; 95% Confidence Interval (CI): -0.05, -0.03), younger age (P<0.001; beta: -0.37; B: -0.03; 95%CI: -0.04, -0.03), taller body height (P = 0.002; beta: 0.06; B: 0.001; 95%CI: 0.000, 0.001), lower level of education of the father (P = 0.001; beta: -0.04; B: -0.01; 95%CI: -0.02, -0.01) and maternal myopia (P<0.001; beta: -0.07; B: -0.04; 95%CI: -0.06, -0.03), and with the ocular parameters of longer ocular axial length (P<0.001; beta: 0.59; B: 0.13; 95%CI: 0.12, 0.14), larger horizontal corneal diameter (P<0.001; beta: 0.19; B: 0.13; 95%CI: 0.11, 0.14), and smaller amount of cylindrical refractive error (P = 0.001; beta: -0.09; B: -0.05; 95%CI: -0.06, -0.04). CONCLUSIONS: Longer CCR (i.e., flatter corneas) (mean:7.84±0.27 mm) was correlated with male sex, younger age, taller body height, lower paternal educational level, maternal myopia, longer axial length, larger corneas (i.e., longer horizontal corneal diameter), and smaller amount of cylindrical refractive error. These findings may be of interest for elucidation of the process of emmetropization and myopization and for corneal refractive surgery.

[Study on the mechanism of polypeptide extract from scorpion venom on inhibition of angiogenesis of H 22 hepatoma].

OBJECTIVE: To explore the mechanism of polypeptide extract from scorpion venom (PESV) on inhibiting angiogenesis. METHODS: The H22 hepatoma tumor model was established by subcutaneously implanting H22 hepatoma cells into mice. The tumor-bearing mice were randomly divided into 4 groups, i.e., the control group, the high dose PESV group, the low dose PESV group, and the 5-fluorouracil (5-Fu) group, 10 mice in each group. The intervention was lasted for 14 days. The growth curve of the tumor volume was drawn and the inhibition rate calculated. Pathological changes of the tumors were observed by HE staining. The microvessel density (MVD) was detected using SP method. The protein expression levels of phosphatidylinositol 3-kinase (P13K), phosphoprotein kinase B (P-Akt), hypoxia-inducible factor-1 alpha (HIF-1 )alpha, and vascular endothelial growth factor-A (VEGF-A) were detected by immunohistochemical assay and Western blot. RESULTS: The tumor inhibitory rate was 64.8%, 43.7%, and 32.4% in the 5-Fu group, the high dose PESV group, and the low dose PESV group. Compared with the control group, the protein expression of PI3K, P-Akt, HIF-1alpha, and VEGF-A were obviously inhibited by PESV and 5-Fu (P <0. 05,P <0. 01). The MVD also decreased in the high and low dose PESV groups (P < 0.05). CONCLUSIONS: PESV could inhibit the angiogenesis of H22 hepatoma. The mechanisms might be associated with suppressing the expression of PI3K, P-Akt, HIF-1 alpha, and VEGF-A.

[Research on the effect and mechanism of polypeptide extract from scorpion venom combined with 5-fluorouracil on vasculogenic mimicry of H22 hepatoma].

OBJECTIVE: To observe the inhibition effects of polypeptide extract from scorpion venom (PESV) combined 5-fluorouracil (5-Fu) on vasculogenic mimicry (VM) of H2 hepatoma carcinoma cells in mice and its possible mechanisms. METHODS: The H22 carcinoma cell suspension was subcutaneously inoculated into 60 Kunming mice. Then tumor-bearing mice were randomly divided into three groups, i.e., the control group, the 5-Fu group, and the combination group (PESV +5-Fu), 20 in each group. The tumor volume was measured once every other day after 14 successive days of intervention. Then the tumor volume growth curve was drawn, and the tumor inhibitory rate was calculated. The morphological changes of the tumor tissue were observed by HE staining. The VM density of each tumor tissue were detected by immunohistochemical assay and periodic acid-schiff stain (PAS). The protein expression levels of hypoxia inducible factor-la (HIF-la) and matrix metalloproteinase-2 (MMP-2) were detected using immunohistochemical assay. The gray value was semi-quantitatively analyzed using LeicaQwinV3 Image Analysis Software. RESULTS: The growth of H22 hepatoma transplantation tumor was inhibited more obviously in the combination group and the 5-Fu group than in the control group (P <0.05). There was statistical difference in the tumor weight and the tumor volume between the combination group and the 5-Fu group (P <0.05). Immunohistochemical assay and PAS showed that the VM density was obviously lower in the combination group than in the control group and the 5-Fu group (P <0.01). Compared with the control group, the protein expressions of HIF-la and MMP-2 significantly decreased in the combination group (P <0.01). CONCLUSIONS: PESV combined 5-Fu could inhibit the generation of VM of H22 hepatoma transplantation tumor in mice. Its mechanisms might be associated with inhibiting the expressions of HIF-lalpha and MMP-2 in the microenvironment of tumors.

Anti-proliferation Effect of Polypeptide Extracted from Scorpion Venom on Human Prostate Cancer Cells in vitro.

BACKGROUND: Prostate cancer is a major cause of cancer-related death in men. Therefore there has been considerable interest to explore neoadjuvant therapy. Polypeptide extracted from scorpion venom (PESV), originally obtained from the East-Asian scorpion Buthus martensi Karsch (BmK), is being studied for both prevention and treatment of various human malignancies including prostate cancer. METHODS: The present study was to investigate the effect of PESV on cell proliferation, cell cycle, and apoptosis in human androgen-independent prostate cancer cells DU-145 in vitro. RESULTS: PESV treatment on these cells resulted in a significantly dose-dependent growth inhibition with a G1 phase arrest at 40µg/mL after 48h treatment. PESV treatment strongly induced expression of p27 (Kip1), but resulted in a decrease in cyclin E, one of cyclins involved in G1 progression. In other studies, PESV treatment also induced high apoptosis index (AI), confirmed by TdTmediated dUTP-biotin nick-end labeling (TUNEL) assay. Further, the apoptosis induction by PESV (40µg/mL) in DU145 cells was associated with an increase of pro-apoptotic protein Bax. CONCLUSIONS: These results suggest that PESV modulates the expression of cell cycle-related and apoptosis-related proteins and induces growth inhibition and apoptosis of DU145 cells, providing a strong rationale for future studies to evaluate prevention or/and intervention strategies for PESV in pre-clinical prostate cancer models. KEYWORDS: Prostate cancer, PESV, cell proliferation, cell cycle, apoptosis.