[Comparison of the analgesic effects of infraspinatus-teres minor interfascial block and interscalene block under ultrasound guidance in patients undergoing arthroscopic shoulder surgery].

Objective: To compare the postoperative analgesic efficacy of ultrasound-guided infraspinatus-teres minor interfascial block and interscalene block in shoulder arthroscopic surgery. Methods: A total of 74 patients undergoing shoulder arthroscopic surgery at the Affiliated Hospital of Jiaxing University from December 2023 to February 2024 were prospectively included, whose age ranged from 18 to 80 years and the American Society of Anesthesiologists (ASA) grade were Ⅰ-Ⅲ. Patients were divided into two groups using block randomization: infraspinatus-teres minor interfascial block group (observation group) and interscalene block group (control group), with 37 cases in each group. In the anesthesia preparation room, all patients received nerve blocks under ultrasound guidance with 20 ml of 0.375% ropivacaine. Patient-controlled intravenous analgesia (PCIA) was administered to all patients following surgery. The primary outcome was the area under the curve (AUC) of the numeric rating scale (NRS) for pain within 24 hours postoperatively. Secondary outcome measures included the highest NRS score within 48 hours postoperatively, the amount of sufentanil used via PCIA within 48 hours postoperatively, the incidence of rescue analgesia and rebound pain, QoR-40 scores, and the rate of postoperative nausea and vomiting within 24 hours. The non-inferiority margin for the AUC of NRS scores between the two types of regional nerve blocks was set at "2.6". Results: A total of 35 patients were included in the observation group [17 males, 18 females, aged (58.1±9.1) years], and 36 patients were included in the control group [12 males, 24 females, aged (57.0±9.8) years]. The AUC of the NRS scores at rest within 24 hours post-operation was 51.7±10.9 in the observation group and 62.6±13.6 in the control group. The difference in AUC between the two groups was -10.9 (95%CI:-16.8--5.1), with the upper limit of the 95%CI falling below the predefined non-inferiority margin of "2.6" (non-inferiority P<0.001). The highest NRS score [M (Q1, Q3)] within 48 hours post-surgery was 3 (3, 4) in the control group, which was significantly higher than the observation group's score of 2 (2, 3) (P<0.001). During the postoperative period of 0-12 hours, the observation group received a median dose of 12 (10, 14) µg of sufentanil, which was significantly higher than the control group's dose of 8 (6, 10) µg (P<0.001). During the postoperative period of 12-24 hours, the observation group received a median dose of 8 (8, 10) µg of sufentanil, which was significantly lower than the control group's median dose of 12 (10, 14) µg (P<0.001). During the postoperative period of 24-48 hours, there was no statistically significant difference in the dose of sufentanil between the two groups of patients (P=0.548). In the observation group, the incidence of rescue analgesia within 48 hours postoperatively was 0 (0/35), which was lower than that of the control group at 22.2% (8/36) (P=0.010). The occurrence of rebound pain in the observation group was 0 (0/35), and the control group was 11.1% (4/36), no statistically significant difference was found between two groups (P=0.130). In the observation group, the QoR-40 score within 24 hours post-operation was 180.2±3.2, which was higher than the control group's score of 175.8±4.7 (P<0.001). There was no statistically significant difference in the incidence of postoperative nausea and vomiting within 24 hours between the two groups (P=0.372). Conclusion: Ultrasound-guided infraspinatus-teres minor interfascial block demonstrates a comparable analgesic effect to interscalene block in shoulder arthroscopic surgery within the first 24 hours postoperatively.

[Efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome].

Objective: To evaluate the efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome. Methods: The Clinical data of 56 patients with Meige syndrome in the Department of Pain Medicine, Affiliated Hospital of Jiaxing University from June 2019 to January 2023 were retrospectively analyzed [19 males and 37 females, aged 42-76 (58.6±8.3) years], including 51 cases of blepharospasm, 3 cases of oromandibular dystonia and 2 cases of blepharospasm concomitant with oromandibular dystonia. CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves was performed on different types of Meige syndrome. And the efficacy and complications of the technique were observed. Results: Fifty-one patients with blepharospasm Meige syndrome underwent CT-guided radiofrequency of facial nerve through bilateral stylomastoid foramen punctures, the symptoms of blepharospasm disappeared completely, leaving bilateral mild and moderate facial paralysis symptoms. Three patients with oral-mandibular dystonia underwent CT-guided radiofrequency therapy by bilateral foramen ovale puncture of mandibular branches of trigeminal nerve, masticatory muscle spasm disappeared, the patients had no difficulty opening the mouth, and the skin numbness in bilateral mandibular nerve innervation area was left. Two cases of Meige syndrome with blepharospasm concomitant with oromandibular dystonia were treated by radiofrequency of facial nerve and mandibular branch of trigeminal nerve, and all symptoms disappeared. The patients were followed up for 1-44 months after the operation, and the symptoms of mild and moderate facial paralysis disappeared at (3.2±0.8) months after the operation, but the numbness did not disappear. Three patients with blepharospasm recurred at the 14, 18 and 22 months after the operation, respectively, while the rest cases did not recur. Conclusions: According to different types of Meige syndrome, CT-guided partial radiofrequency ablation of responsible cranial nerves can effectively treat the corresponding type of Meige syndrome. The complications are only mild and moderate facial paralysis which can be recovered, and/or skin numbness in the mandibular region.

[Study on reproductive toxicity of nano-cadmium sulfide with different particle sizes on male mice].

Objective: To investigate the reproductive toxicity of cadmium sulfide nanoparticles (Nano-CdS) with different particle sizes on male mice. Methods: In January 2019, 30 SPF grade male mice were randomly divided into a control group, an experimental group[CdS Ⅰ group (particle size approximately 5 nm), and a CdS Ⅱ group (particle size approximately 50 nm) ], with 10 mice in each group. The experimental group was orally gavaged with 100 mg/kg, once a day, while the control group was gavaged with an equal volume of physiological saline for 45 consecutive days. After 45 days, levels of cadmium accumulation in testis were determined directly by AAS, deformity and testicular histopathological changes were also observed. Serum testosterone levels were measured by enzyme-linked immunosorbentassay (ELISA), expression levels of P450scc, 17ß-HSD and P450c17 mRNA were determined by real-time PCR. P450c17 protein was determinated by Western Blot. Results: The histopathological results showed that the testes of the experimental group mice showed varying degrees of damage; Ultrastructural observation showed that the ultrastructure of mouse testicular cells in each experimental group showed varying degrees of mitochondrial expansion and disappearance of cristae, as well as irregular nuclear membranes. The degree of damage in CdS Ⅰ group was milder than that in CdS Ⅱ group. Compared with the control group, the cadmium content in the testes of the CdS Ⅰ and CdS Ⅱ groups significantly increased (P=0.001, 0.001), and the CdS Ⅱ group was higher than the CdS Ⅰ group (P=0.001). Compared with the control group, the levels of testosterone in the CdS Ⅰ and CdS Ⅱ groups decreased with statistical significance (P=0.001, 0.001). Real time fluorescence quantitative PCR results showed that compared with the control group, the experimental group's P450scc, 17ß-HSD. The expression levels of 17ß-HSD and P450c17 mRNA were significantly reduced, with statistically significant differences (P=0.001, 0.001, 0.001), and CdS Ⅱ group 17ß-HSD. The expression levels of 17ß-HSD and P450c17 mRNA were significantly lower than those of CdS Ⅰ group (P=0.001, 0.036). The Western Blot assay results showed that the expression levels of P450c17 protein in the testes of CdS Ⅰ and CdS Ⅱ groups of mice were significantly reduced, with statistical significance (P=0.001, 0.001) ; And the CdS Ⅱ group was significantly lower than the CdS Ⅰ group (P=0.001). According to Spearman correlation analysis, testosterone levels are correlated with P450scc, P450c17, 17ß-HSD mRNA. There is a highly positive correlation between 17ß-HSD mRNA levels, with statistically significant differences (r(s)=0.88, 0.80, 0.70, P=0.001, 0.001, 0.004) . Conclusion: Nano cadmium sulfide may induce reproductive toxicity by reducing the expression levels of key enzyme genes and enzyme protein activity in testosterone and its synthesis in mice, and the CdS Ⅱ group has a stronger toxic effect.

Abdominal girth and dorso-sacral distance can be used to estimate lumbosacral cerebral fluid volume.

BACKGROUND: Patients' abdominal girth and vertebral column length are highly correlated with the spread of local anaesthetics after spinal anaesthesia. Lumbosacral cerebrospinal fluid volume is the primary determinant for spinal spread. Thus, we attempted to verify the hypothesis that abdominal girth and dorso-sacral distance are correlated with lumbosacral cerebrospinal fluid volume. METHODS: Forty-five healthy volunteers were enrolled in this study to measure lumbosacral cerebrospinal fluid volume using magnetic resonance imaging. The age, height, weight, abdominal girth, dorso-sacral distance and lumbosacral cerebrospinal fluid volume of the volunteers were recorded. Multiple linear regression analysis was used to analyse the correlation between age, height, weight, abdominal girth, dorso-sacral distance and lumbosacral cerebrospinal fluid volume. RESULTS: Two volunteers were excluded because of lumbar disc herniation, leaving 43 volunteers for analysis. Multiple linear regression analysis showed a strong correlation between abdominal girth, dorso-sacral distance and lumbosacral cerebrospinal fluid volume (both P < 0.01). The adjusted R2 was 0.644. Volunteers with small abdominal girth showed clear images of cerebrospinal fluid in the nerve root cuff at the intervertebral foramen in the three-dimensional magnetic resonance imaging reconstruction of lumbosacral cerebrospinal fluid, while the images were vague in volunteers with large abdominal girth. Clearer images implied larger lumbosacral cerebrospinal fluid volume, while vaguer images, smaller lumbosacral cerebrospinal fluid volume. CONCLUSIONS: Multiple regression analysis revealed that abdominal girth and dorso-sacral distance were correlated with lumbosacral cerebrospinal fluid volume. Smaller abdominal girths and larger dorso-sacral distances predict larger lumbosacral cerebrospinal fluid volume.

[Chromosome aberration and micronucleus frequency in peripheral blood lymphocytes in radiation workers].

OBJECTIVE: To investigate chromosome aberration and micronucleus frequency in peripheral blood lymphocytes in workers engaged in radiation for a long time, to reduce occupational hazard caused by ionizing radiation, and to further strengthen health surveillance. METHODS: A total of 366 members of medical staff engaged in radiation work who underwent physical examinations in Hangzhou Hospital of Prevention and Treatment of Occupation Diseases from 2014 to 2015 were enrolled as radiation group, consisting of staff engaged in X-ray diagnosis, diagnostic radiology, radiotherapy, and interventional radiology. Another 100 members of medical staff without exposure to radiation were enrolled as control group. Whole blood culture was used to measure chromosome aberration and micronucleus frequency in peripheral blood lymphocytes. RESULTS: The radiation group had a significantly higher rate of chromosome aberration than the control group (0.30% vs 0.09% , χ(2)= 13.43, P<0.01), as well as a significantly higher micronucleus frequency than the control group (2.09‰ vs 0.08‰, χ(2)=74.4, P<0.01). The abnormal rates of chromosome aberration and micronucleus showed no significant differences across radiation workers with different working years (P>0.05). The staff engaged in X-ray diagnosis, diagnostic radiology, radiotherapy, and interventional radiology had rates of chromosome aberration of 0.25%, 0.25%, 0.23%, and 0.41%, respectively, which showed a significant difference between the staff at these four posts (χ(2)=8.22, P<0.05); the micronucleus frequencies in the staff at these four posts were 1.36‰, 1.28‰, 1.14‰, and 3.79‰, respectively, and showed a significant difference between the staff at these four posts (χ(2)=251.09, P<0.01). CONCLUSION: Radiation workers are exposed to lowdose ionizing radiation for a long time, which may cause significant increases in the rate of chromosome aberration and micronucleus frequency in peripheral blood lymphocytes.

Antineoplastic therapy combined with whole brain radiation compared with whole brain radiation alone for brain metastases: a systematic review and meta-analysis.

BACKGROUND: The standard treatment for brain metastases is whole brain radiation, but the medium survival is about 3-10 months and hadn't be improved for years. AIM: This study was to evaluate the effect of antineoplastic therapy combined with whole brain radiation for brain metastases. MATERIALS AND METHODS: We searched PubMed, EMBASE, Cochrane Library, Chinese Biomedical Literature Database, China Journal Full Text Database and references of the included studies up to May 2011. Randomized controlled trials involving antineoplastic combined with whole brain radiation compare with whole brain radiation alone for brain metastases were analysed. Study selection, data collection and quality assessment of studies were performed by two individual reviewers according to the Cochrane Handbook for systematic reviews of interventions 5.0.2. Statistic analyses were calculated using RevMan5.0.17 software. 9 randomized controlled trails, a total of 1582 patients were included. RESULTS: There were no significant differences in overall survival, six to twenty-four months survival rate and death from central nervous system (CNS) cause, only the objective response rate was statistically higher in the combined group. (RR = 1.47, 95% CI: 1.10, 1.97; p = 0.009) Subgroup analysis of lung cancer got the same result, except that death from central nervous system (CNS) cause was higher in the combined therapy group, it was statistical significant (RR = 0.70, 95% CI: 0.53, 0.93; p = 0.01). CONCLUSIONS: The benefit of antineoplastic combined with whole brain radiation for brain metastases was not concerned, either in the brain metastases from unselected primary tumors or lung cancer.

[A multicenter epidemiological study of acute bacterial meningitis in children].

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum ß-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.

Prediction of potential therapeutic drugs against SARS-CoV-2 by using Connectivity Map based on transcriptome data.

OBJECTIVE: Transcriptome data related to severe acute respiratory syndrome-related coronavirus 2 (a novel coronavirus discovered in 2019, SARS-CoV-2) in GEO database were downloaded. Based on the data, influence of SARS-CoV-2 on human cells was analyzed and potential therapeutic compounds against the SARS-CoV-2 were screened. MATERIALS AND METHODS: R package "DESeq2" was used for differential gene analysis on the data of cells infected or non-infected with SARS-CoV-2. The "ClusterProfiler" package was used for GO functional annotation and KEGG pathway enrichment analysis of the differentially expressed genes (DEGs). A protein-protein interaction (PPI) network of the DEGs was constructed through STRING website, and the key subset in the PPI network was identified after visualization by Cytoscape software. Connectivity Map (CMap) database was used to screen known compounds that caused genomic change reverse to that caused by SARS-CoV-2. RESULTS: By intersecting DEGs in two datasets, a total of 145 DEGs were screened out, among which 136 genes were upregulated and 9 genes were downregulated in SARS-CoV-2-infected cells. Functional enrichment analyses revealed that these genes were mainly associated with the pathways involved in viral infection, inflammatory response, and immunity. The CMap research found that there were three compounds with a median_tau_score less than -90, namely triptolide, tivozanib and daunorubicin. CONCLUSIONS: SARS-CoV-2 can cause abnormal changes in a large number of molecules and related signaling pathways in human cells, among which IL-17 and TNF signaling pathways may play a key role in pathogenic process of SARS-CoV-2. Here, three compounds that may be effective for the treatment of SARS-CoV-2 were screened, which would provide new options for improving treatment of patients infected with SARS-CoV-2.

miR-34b inhibits the migration/invasion and promotes apoptosis of non-small-cell lung cancer cells by YAF2.

OBJECTIVE: Lung cancer is the leading cause of cancer death in the world and microRNAs (miRNA) have been found to be involved in the initiation and development of cancer by acting as potential oncogenes or tumor suppressor genes. PATIENTS AND METHODS: In this study, we investigated the expression of miR-34b in non-small cell lung cancer (NSCLC) patients and discussed the molecular mechanism of miR-34b in the invasion and migration of A549 cells in vitro. RESULTS: Our results showed that miR-34b was significantly down-regulated in primary cancer tissues when compared with the normal lung tissues. The over-expression of miR-34b inhibited migration and invasion, and promoted apoptosis of A549 lung cancer cells. Furthermore, Luciferase reporter assay validated YY1-associated factor 2 (YAF2) as a direct target of miR-34b and YAF2 expression was significantly increased in clinical NSCLC tissue samples. In addition, the over-expression of miR-34b inhibited YAF2, p-Jak2, p-STAT3 and MMP2 protein expression and promoted caspase 3 protein expression in cancer cells. CONCLUSIONS: Our results suggest that miR-34b may inhibit migration and invasion of NSCLC cells by targeting YAF2. Thus, our findings provide new insight into the molecular mechanisms of lung cancer metastasis and miR-34b may serve as a potential target in the treatment of human lung cancer.

Mir-595 is a significant indicator of poor patient prognosis in epithelial ovarian cancer.

OBJECTIVE: MiR-595 has been demonstrated to be involved in tumorigenesis of several cancers. However, the clinical significance of miR-595 in epithelial ovarian cancer (EOC) remains unclear. The aim of this study was to explore the correlation of miR-595 expression with clinicopathologic features and prognosis in EOC patients. PATIENTS AND METHODS: Quantitative Real-time PCR (qRT-PCR) was performed to evaluate the expression level of miR-595 in all participants. Correlations between miR-595 levels and clinicopathological factors were investigated. Association of miR-595 expression with overall survival was estimated by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed. RESULTS: We observed that miR-595 was downregulated in EOC tissues in comparison with noncancerous ovarian tissues (p < 0.05). In addition, low miR-595 expression level was significantly associated with advanced FIGO stage (p = 0.003), distant metastasis (p = 0.002), and grade (p = 0.014). Furthermore, significantly shorter overall survival was observed in patients with lower expression of the miR-595. At last, multivariate analysis revealed that decreased expression of miR-595 was an independent predictor of overall survival of EOC patients. CONCLUSIONS: Our data indicated that miR-595 expression might be a novel potential prognostic biomarker for EOC.

Enhanced toxicity to the cyanobacterium Microcystis aeruginosa by low-dosage repeated exposure to the allelochemical N-phenyl-1-naphthylamine.

It has been puzzling whether and how a plant could exert a strong allelopathic inhibition to the target organisms by releasing low concentrations of allelochemicals. Plant allelochemicals have been proposed to be released continuously, however, direct evidence from specific allelochemicals is urgently required. In the present study, the toxicity of allelochemical N-phenyl-1-naphthylamine (NPN) towards the cyanobacterium Microcystis aeruginosa by two different exposure patterns was compared. One was low-dosage repeated exposure (LRE), in which 50  µg L-1 NPN was repeatedly dosed to simulate the continual release of allelochemicals, and the other one was high-dosage single exposure (HSE) as per the routine toxicity assay. The results showed a significant growth inhibition to M. aeruginosa in the LRE group, where the inhibition rate reached above 90% from day 6 to day 9. The cell-membrane damage ratio increased from 64.05% on day 5 up to 96.60% on day 9. PSII photosynthesis activity expressed as Fv/Fm, ΦPSII, NPQ and ETRmax was also thoroughly inhibited in this group. Whereas the growth and PSII photosynthesis activity of M. aeruginosa in the HSE group were inhibited initially, but recovered gradually from day 4 or 5, which was accompanied by a continuous reduction of NPN content in culture solutions. Although NPN content in the LRE group was relatively lower, it remained at a more stable level throughout the experiment. These results indicate that continual release of low-dosage allelochemicals by aquatic plants plays crucial roles in their potent inhibition against cyanobacteria. Low-dosage continual exposure pattern needs to be investigated further.

Cell membrane signaling as target in cancer therapy: inhibitory effect of N,N-dimethyl and N,N,N-trimethyl sphingosine derivatives on in vitro and in vivo growth of human tumor cells in nude mice.

Sphingosine (SPN) has been claimed to be a negative modulator of transmembrane signaling through protein kinase C (PK-C) or some yet unidentified mechanism [for review see Y. A. Hannun and R. M. Bell, Science (Washington DC), 243: 500-507, 1989]. N,N-Dimethylsphingosine (DMS) was recently found to be a physiological cellular component and, in comparison to SPN, to show a stronger and stereospecific inhibitory effect on PK-C activity of A431 cells (for review see Y. Igarashi, Trends Glycosci. Glycotechnol., 2: 319-332, 1990; and S. Hakomori, J. Biol. Chem., 265: 18713-18716, 1990). (4E)-N,N,N-Trimethyl-D-erythro-sphingenine (TMS) is not detectable as a normal cellular component; however, it is expected to exhibit potent activity because of its quaternary ammonium ion structure, and in fact it showed much stronger inhibitory effect than DMS or SPN on PK-C activity (which plays an important role in cell growth regulation) in vitro. In view of these findings, we investigated the effects of SPN, DMS, and TMS on in vitro growth of various human carcinoma cell lines and on in vivo tumor growth in athymic nu/nu mice. Both DMS and TMS showed similar in vitro and in vivo growth inhibitory effects on tumor cells, despite the fact that TMS showed a much stronger inhibitory effect than DMS on PK-C activity of A431 cells. In contrast, SPN showed only a weak effect on in vitro cell growth and no effect on in vivo tumor growth. Tumor growth following s.c. inoculation of mice with human gastric carcinoma cell line MKN74 was inhibited in a dose-dependent manner by DMS, and tumor size was decreased after three or four consecutive daily injections of 0.5-mg doses of DMS or TMS. Increased tumor growth occurred after administration of these compounds was stopped; however, size of tumor remained significantly smaller than in groups treated with SPN or control saline. The effect of DMS or TMS on in vitro or in vivo MKN74 cell growth was stronger than that of 8-chloro-adenosine-cyclic 3':5'-monophosphate dihydrate, the most promising agent currently being used in clinical trials for inhibition of tumor growth by induction of differentiation. These results suggest that DMS or TMS could be useful anticancer agents through modification of transmembrane signaling related to cancer cell growth.

Cell membrane signaling as target in cancer therapy. II: Inhibitory effect of N,N,N-trimethylsphingosine on metastatic potential of murine B16 melanoma cell line through blocking of tumor cell-dependent platelet aggregation.

Two phenotypic parameters, aberrant expression of protein kinase C and tumor cell-induced platelet aggregation (PA), have been correlated with abnormal growth behavior and metastatic potential of tumor cells. We recently observed that N,N,N-trimethylsphingosine (TMS) and N,N-dimethylsphingosine (DMS), but not sphingosine (SPN), had an inhibitory effect (via blocking of transmembrane signaling) on the growth of various human tumor cell lines in vitro as well as in vivo in nu/nu mice (K. Endo et al., Cancer Res., 51: 1613-1618, 1991). We therefore investigated the effects of TMS, DMS, and SPN on (a) PA induced by ADP and thrombin; (b) PA induced by melanoma cell line B16/BL6; and (c) experimental lung colonization as well as spontaneous lung metastasis of BL6 cells in syngeneic C57BL/6 mice. In experiments on agonist-induced PA, TMS inhibited PA and ATP secretion 5-fold more strongly than DMS or SPN. This effect may be based on the inhibition of Mr 47,000 platelet protein phosphorylation and/or inhibition of phosphatidylinositol turnover as a transmembrane signaling pathway in platelets. Tumor cell (BL6 melanoma)-induced PA and ATP secretion were also strongly inhibited by TMS, but not by DMS or SPN. Unlike ADP- or thrombin-induced PA, BL6 cell-induced PA was not inhibited by Calphostin-C (a potent protein kinase C inhibitor) or cilostazol (a potent inhibitor of PA based on inhibition of cyclic AMP phosphodiesterase). Since many previous studies suggested that the ability of tumor cells to induce PA is related to the degree of malignancy (e.g., metastatic potential) of tumor cells, we studied the effect of TMS on lung metastatic potential. Three independent sets of experiments, as described below, all showed clear inhibition of lung metastasis by administration of TMS: (a) i.v. coinjection of BL6 melanoma cells and TMS; (b) i.v. injection of TMS and, 1 h later, BL6 cells; (c) spontaneous metastasis to lung from s.c. BL6 tumor (TMS administered after establishment of tumor, followed by resection of tumor). In comparison to tumor growth inhibition produced by TMS or DMS, inhibition of melanoma metastasis by TMS is obvious at lower doses.

[Laboratory diagnosis of chronic granulomatous disease].

OBJECTIVE: To evaluate the methods of flow cytometric-dihydrorhodamine 123 (DHR) analysis, gp91 protein detection, gene mutation analysis for the precise diagnosis of chronic granulomatous disease (CGD). METHOD: Clinical and laboratory data of patients with CGD confirmed by gene mutation analysis from 2008 to 2015 in Children's Hospital of Fudan University were retrospectively reviewed.The results of respiratory burst, gp91 protein level, and gene mutations were analyzed.The relationships among these three methods were explored. RESULT: A total of 138 patients of CGD with confirmed gene mutation were included in this study, of them, 123 cases(89.1%) had CYBB gene mutation, 4 cases(2.9%) had CYBA mutation, 5 cases(3.6%) had NCF1 mutation and 6 cases(4.4%) had NCF2 mutation.The range of stimulatory index (SI) was 0.8-60.5, the 25 th, 50 th, 75th percent was 1.7, 2.7, 4.7; 112 cases had the results of gp91, of them, 100 with gp91(0,) 2 with gp91(-), and 10 with gp91(+) . Six mutations, which were not reported before, were c. 76-77delTT, c. 343-344delCA, c. 481A>T, c. 1152G>C, c. 1613G>A for CYBB gene, and c. 137T>G for NCF2 gene. Among CGD patients with CYBB mutation, SI of patients with gp91(+) was higher than patients with gp91(0) 14.6 vs. 2.5(t=44.21, P=0.004). Patients of NCF1 mutation had higher SI than patients with CYBB mutation, 17.7 vs. 2.5 (t=60.8, P=0.003). CONCLUSION: Flow cytometric-DHR analysis and gp91 protein detection are important diagnostic methods for CGD, they could help the precise diagnosis of CGD.Different mutation types, different mutation genes could have impact on the results of respiratory burst and gp91 level.The application of diagnostic technology from function, protein to gene analysis could help precise diagnosis of CGD.

The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials.

BACKGROUND: The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically. PATIENTS AND MATERIALS: Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects. RESULTS: Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64-0.99) and disease control rate (RR 0.90; 95 % CI 0.82-0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91-1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86-1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups. CONCLUSION: The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.

Results of air pressure enema reduction of intussusception: 6,396 cases in 13 years.

Intussusception is the most common surgical emergency of childhood in China. Over the past 10 years, the incidence of intussusception has steadily increased world-wide, as well as in China. For example, 279 cases were treated in the Shanghai Children's Hospital in 1974, while 615 were treated in 1984. Twelve cases were treated in a course of a single night during 1985. Over the past 13 years, for which we have good records, 6,396 cases of intussusception were treated at the Shanghai Children's Hospital. Males outnumber females by a ratio of 2 to 1. In 3,872 cases seen over the past 6 years, 35.1% were under 6 months of age, 65.9% less than 1 year of age, and 88.4% less than 2 years of age.

Clinical application of DSA and evaluation of its methods: analysis of 160 cases and review of literature.

A total of 160 patients of two hospitals received 192 DSA examinations with different contrast administrations, and techniques of performing DSA were analyzed, compared, and evaluated with reference to the literature. It was concluded that (1) the peripheral injection of contrast material for IVDSA via cannula is simpler than that via a short catheter, but the incidences of contrast extravasation in both cases are higher than with central injection. (2) Both the lower part of the superior vena cava and the right atrial cavity are safe sites for central injection. With central injection for IVDSA, the arterial iodine concentration is approximately double that of peripheral injection, and consistent high quality examinations of the intracranial vessels may be obtained. However, neither peripheral nor central injections can visualize the small vessels clearly. (3) IVDSA may be substituted for conventional angiography only in examinations of the aorta and its main branches. (4) IADSA is becoming a superior angiographic technique and its clinical application is increasing. In addition, means of avoiding contrast extravasation during IVDSA and the main points of selecting the optimal technique for DSA are described in this paper.