[CT texture analysis for predicting pseudoprogression in metastatic clear cell renal cell carcinoma during PD-1 inhibitor therapy].

Objective: To evaluate the effectiveness of enhanced CT texture feature analysis in predicting pseudoprogression in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing programmed cell death protein 1 (PD-1) inhibitor therapy. Methods: A cross-sectional study. Data from 32 patients with mccRCC were retrospectively collected who received monotherapy with PD-1 inhibitors after standard treatment failure at Henan Cancer Hospital, from June 2015 to January 2021. Clinical information and enhanced CT images were analyzed to assess target lesion response. The lesions were divided into pseudoprogression and non-pseudoprogression groups. Manual segmentation of target lesions was performed using ITK-Snap software on baseline enhanced CT, and texture analysis was conducted using A.K. software to extract feature parameters. Differences in texture features between the pseudoprogression and non-pseudoprogression groups were analyzed using univariate and multivariate logistic regression. A predictive model for pseudoprogression was constructed, and its performance was evaluated using ROC curve analysis. Results: A total of 32 patients with 89 lesions were included in the study. Statistical analysis revealed significant differences in seven texture features between the pseudoprogression and non-pseudoprogression groups. These features included"original_ngtdm_Strength"(0.49 vs. -0.61,P=0.006), "wavelet-HLH_glszm_ZonePercentage"(0.67 vs. -0.22,P=0.024),"wavelet-LHL_ngtdm_Strength"(1.20 vs. -0.51,P=0.002), "wavelet-HLL_gldm_LargeDependenceEmphasis"(-0.84 vs. 0.19,P=0.002), "wavelet-HLH_glcm_Id" (-0.30 vs. 0.43,P=0.037),"wavelet- HLH_glrlm_RunPercentage"(0.45 vs. -0.01,P=0.032),"wavelet-LHH_firstorder_Skewness"(0.25 vs. -0.27, P=0.011). Based on these features, a pseudoprogression prediction model was developed with a P-value of 0.000 2 and an odds ratio of 0.045 (95%CI 0.009-0.227). The model exhibited a high predictive performance with an AUC of 0.907 (95%CI 0.817-0.997) according to ROC curve analysis. Conclusions: Enhanced CT texture feature analysis shows promise in predicting lesion pseudoprogression in patients with metastatic ccRCC undergoing PD-1 inhibitor therapy. The developed predictive model based on texture features demonstrates good performance and may assist in evaluating treatment response in these patients.

[Modification factors associated with maternally inherited non-syndromic hearing loss].

Mutations in the mitochondrial DNA have been certified to be one of the most important causes of maternally inherited sensorineural hearing loss. Among these, mitochondrial 12S rRNA1555A>G, 1494C>T and other mutations are associated with both nonsyndromic and drug induced hearing loss caused by aminoglycosides. Individuals carrying 1555A>G or 1494C>T mutation have a variety of clinical manifestations, which implies that the 1555A>G or 1494C>T mutation is a chief factor underlying the development of deafness but insufficient to produce the clinical phenotype. Therefore other modifier factors, such as aminoglycosides, mitochondrial haplotypes, secondary mutation or nuclear modifier genes, may play an important role in the phenotypic expression of the deafness-associated mitochondrial 12S rRNA1555A>G or 1494C>T mutation. In this review, the modifier factors for the phenotypic expression of deafness-associated mitochondrial 12S rRNA1555A>G or 1494C>T mutations were summarized and proposed the pathogenesis of maternally inherited deafness.

[Mutation analysis of GJB2 gene in 1 822 patients with nonsyndromic hearing loss in Zhejiang Province].

Objective:To analyze the genetic characteristics in nonsyndromic hearing impairment (NSHL) patients in Zhejiang province.Method:Peripheral blood samples were obtained from 1822 NSHL patients and 467 normal hearing controls in Zhejiang province. We carried out a systematic mutational screening of GJB2 gene in these subjects by amplifying the coding region of GJB2 gene and sequencing directly.Result:Thirty kinds of mutation were identified, including eleven pathogenic mutations, one hypomorphic allele, sixteen polymorphic mutations and two novel mutations. The c.235delC mutation was the most prevalent pathogenic mutation in this cohort (18.50%), and the rate of allele mutation was 12.16%. The frequency of c.299_300delAT,c.176_191del16,c.512_513insAACG,c.35delG,c.283G>A,c.427C>T,c.35insG,c.439G>A,c.571T>C,c.139G>T mutations were decreased in turn.Conclusion:c.235delC mutation is the hot spot of GJB2 gene mutation in NSHL patients in Zhejiang province and the most common mutational pattern is frame-shift mutation. The discovery of novel mutations enriches the spectrum and frequency of variants in GJB2 gene.

[Dose optimization of lipid infusionin treatment of patients with acute dexmedetomidinepoisoning].

OBJECTIVE: To optimize the dose of lipid infusion in treatment of patients with acute dexmedetomidinepoisoning, in order to further guide the rational use of medication in clinical practice. METHODS: A total of 80 patients with acute dexmedetomidinepoisoning were admitted in this study from January 2012 to October 2014 at our hospital and divided into three groups based on the intensity of poisoning, including: slight poisoning (28 cases), moderate poisoning (32 cases) and severe poisoning (20 cases). Patients in each group were given 10% lipid infusion or 20% lipid infusion for treatment.Stable blood dexmedetomidineconcentrations of patients in pre-treatment and at different time points after treatment (pre-treatment and 0.5, 1, 2, 5, 10, 20 h after treatment) and the length of hospital stay, awake time in each group were investigated and compared.Ramsay sedation scores were recorded and compared in different time points (0.5 h before treatment and 2, 5, 20 h after treatment) in each group for different treatments.Side effects and complications were recorded, and follow-up was conducted during 1-3 d post discharge to record the recovery condition in patients. RESULTS: In each group, patients receiving 20% lipid infusion waked earlier than those receiving 10% lipid infusion.And the hospitalization duration for patients receiving 20% lipid infusion was significantly shorter than those receiving 10% lipid infusion [(4.6±1.6) h vs (6.7±2.0) h, (2.6±0.4) d vs (4.0±0.6) d, P<0.05]. The Ramsay sedation scores were significantly lower for patients receiving 20% lipid infusion than those receiving 10% lipid infusionat 2 h and 5 h after treatment in each group [(3.4±0.3) vs (4.7±0.4), (2.6±0.3) h vs (3.5±0.3) h, P<0.05]. The stable plasma concentrations of dexmedetomidine were gradually reduced after the treatment, and which were lower when compared with the theoretical metabolic concentration.What's more, the plasma concentrationsat 1 h, 2 h and 5 h after treatment were significantly lower for patientsreceiving 20% lipid infusion than those receiving 10% lipid infusion in each group (P>0.05). All patients in our study were cured and discharged without severe side effects and complications, and follow-ups showed that no patients showed evidence of rebound phenomenon. CONCLUSIONS: Different concentrations of lipid infusionare safe and effective in relieving the intensity of dexmedetomidinepoisoning, and promoting the clinical recovery.What's more, the therapeutic efficacy of 20% lipid infusion is greater than 10% lipid infusion.

[Spectrum of GJB6 variants in 318 pedigrees with non-syndromic hearing loss:one deafness pedigree carrying both GJB6 and GJB2 deletion variant].

Objective:To investigate the mutation characteristics of GJB6 (gap juction bata 6) gene in 318 Han Chinese pedigrees with non-syndromic hearing loss.Method:Polymerase chain reaction was used to detect the coding region of GJB6 gene in 318 Han Chinese pedigrees with non-syndromic hearing loss.Gene arrays and second generation sequencing were used to detect 118 genes which had reported to be accosiated with deafness in members of pedigree which possibly carried pathogenic GJB6 gene mutation.Result:Here,we have screened the mutations of GJB6 gene in 318 Han Chinese pedigrees with non-syndromic hearing loss and found one pedigree carrying both GJB6 and GJB2 gene deletion.Clinical and molecular genetic evaluation revealed the variable phenotype of hearing impairments including age-at-onset,audiometric configuration and severity in these subjects.Mutational analysis of the GJB2 and GJB6 gene coding region showed a heterozygous 235 del C of GJB2 gene and a novel 228 del G of GJB6 gene.Conclusion:GJB6 gene 228 del G variant,which occurs at a highly evolutionarily conserved nucleotide,forward the stop codon to 81 position and result in the corresponding polypeptide 181 amino acids shorter than wildtype polypeptide.In addition,GJB6 gene 228 del G absent varies among 94 unrelated Chinese controls.Our finding suggest that GJB6 gene 228 del G maybe a novel pathogenic mutation associated with non-syndromic hearing loss.

Electroacupuncture inhibits excessive interferon-γ evoked up-regulation of P2X4 receptor in spinal microglia in a CCI rat model for neuropathic pain.

BACKGROUND: Although electroacupuncture (EA) is effective in the relief of neuropathic pain, the underlying mechanisms remain unclear. Previous studies have reported immunomodulatory effects of EA in rats. Since excessive release of interferon-γ (IFN-γ) after nerve injury transforms quiescent spinal microglia into an activated state with more neuropathic pain, associated with purinergic receptor P2X4 expression, it is possible that EA may mediate its analgesic effect by attenuating IFN-γ release and subsequent generation of P2X4R(+) microglia. METHODS: Male rats underwent chronic constriction injury (CCI) or IFN-γ intrathecal injection and von Frey tests were performed to evaluate the effect of EA on pain thresholds. Spinal IFN-γ and P2X4R expression levels were measured by immunohistochemistry, real-time PCR, enzyme immunoassay, and/or western blots. In vitro primary cultures of microglia were used to examine IFN-γ activation of P2X4R(+) cells. RESULTS: In CCI rats, EA treatment significantly increased paw withdrawal threshold relative to control. IFN-γ facilitated P2X4R(+) microglia activation both in vitro and in vivo. EA also down-regulated both P2X4R and IFN-γ expression in the spinal cord after CCI. However, EA did not exert the same analgesic effect after intrathecal IFN-γ injection. CONCLUSIONS: EA ameliorated tactile allodynia after peripheral nerve injury by down-regulating excessive expression of IFN-γ in the spinal cord and subsequently reducing expression of P2X4R.

Transmission of avian influenza A(H7N9) virus from father to child: a report of limited person-to-person transmission, Guangzhou, China, January 2014.

We investigated a possible person-to-person transmission within a family cluster of two confirmed influenza A(H7N9) patients in Guangzhou, China. The index case, a man in his late twenties, worked in a wet market that was confirmed to be contaminated by the influenza A(H7N9) virus. He developed a consistent fever and severe pneumonia after 4 January 2014. In contrast, the second case, his five-year-old child, who only developed a mild disease 10 days after disease onset of the index case, did not have any contact with poultry and birds but had unprotected and very close contact with the index case. The sequences of the haemagglutinin (HA) genes of the virus stains isolated from the two cases were 100% identical. These findings strongly suggest that the second case might have acquired the infection via transmission of the virus from the sick father. Fortunately, all 40 close contacts, including the other four family members who also had unprotected and very close contact with the cases, did not acquire influenza A(H7N9) virus infection, indicating that the person-to-person transmissibility of the virus remained limited. Our finding underlines the importance of carefully, thoroughly and punctually following-up close contacts of influenza A(H7N9) cases to allow detection of any secondary cases, as these may constitute an early warning signal of the virus's increasing ability to transmit from person-to-person.

Development of anti-influenza A compounds: a pilot study.

1. There is no effective anti-H5N1 avian influenza agent. 2. A chemical compound­ BFDBSC­can inhibit H5N1 virus infection in cell cultures, and such inhibition might be attributable to its halogenated benzoyl residues. 3. This pilot study assessed anti- H5N1 activity and toxicity of four chemical compounds with halogenated benzoyl residues in cell culture system. 4. Two compounds­FPBFDBSC and BFB-gallate­ showed higher antiviral effectsthan BFDBSC, whearas the other two­BFB-borneol and BFB-menthol­showed lower antiviral effects. These compounds did not show toxicity. 5. The halogenated benzoyl residues may play a key role in anti-H5N1 effects. However, all these compounds showed poor solubility, which may limit their utility

Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses.

BACKGROUND: The novel swine-origin influenza A H1N1 virus (S-OIV) causes the current pandemic. Its tissue tropism and replication in different cell lines are not well understood. OBJECTIVE: Compare the growth characteristics of cell lines infected by S-OIV, seasonal influenza A H1N1 (sH1N1) and avian influenza A H5N1 (H5N1) viruses and the effect of temperature on viral replication. STUDY DESIGN: Cytopathic effect (CPE), antigen expression by immunofluorescence (IF) and viral load profile by quantitative RT-PCR in 17 cell lines infected by S-OIV, sH1N1 and H5N1 were examined. Comparison of their replication efficiency in chick embryo was performed. The effect of temperature on viral replication in Madin-Darby canine kidney (MDCK) cells was determined by TCID(50) at 33 degrees C, 37 degrees C and 39 degrees C for 5 consecutive days. RESULTS: S-OIV replicated in cell lines derived from different tissues or organs and host species with comparable viral load to sH1N1. Among 13 human cell lines tested, Caco-2 has the highest viral load for S-OIV. S-OIV showed a low viral load with no CPE or antigen expression in pig kidney cell PK-15, H5N1 demonstrated the most diverse cell tropism by CPE and antigen expression, and the highest viral replication efficiency in both cell lines and allantoic fluid. All three viruses demonstrated best growth at 37 degrees C in MDCK cells. CONCLUSION: Cell line growth characteristics of S-OIV, sH1N1 and H5N1 appear to correlate clinically and pathologically with involved anatomical sites and severity. Low replication of S-OIV in PK-15 suggests that this virus is more adapted to human than swine.

Examination of seroprevalence of coronavirus HKU1 infection with S protein-based ELISA and neutralization assay against viral spike pseudotyped virus.

BACKGROUND: Human coronavirus HKU1 (HCoV-HKU1) is a recently identified coronavirus with a global distribution and known to cause mainly respiratory infections. OBJECTIVES: To investigate the seroepidemiology of HKU1 infections in our local population. STUDY DESIGN: An ELISA-based IgG antibody detection assay using recombinant HCoV-HKU1 nucleocapsid and spike (S) proteins (genotype A) were developed for the diagnosis of CoV-HKU1 infections, Additionally, a neutralization antibody assay using the HCoV-HKU1 pseudotyped virus was developed to detect the presence of neutralizing antibodies in serum with antibody positivity in an S protein-based ELISA. RESULTS: Results of the recombinant S protein-based ELISA were validated with Western blot, immunofluorescence analysis and flow cytometry. The coupled results demonstrated good correlation with Spearmen's coefficient of 0.94. Seroepidemiological study in a local hospital-based setting using this newly developed ELISA showed steadily increasing HCoV-HKU1 seroprevalence in childhood and early adulthood, from 0% in the age group of <10 years old to a plateau of 21.6% in the age group of 31-40 years old. CONCLUSIONS: Our study demonstrated the usefulness of the S-based ELISA which could be applied to future epidemiological studies of HCoV-HKU1 in other localities.