ABSTRACT
Objective: To explore the correlation between MYB/NFIB gene fusion and clinicopathological features such as tumor grade and prognosis of head and neck adenoid cystic carcinoma (ACC), and to assess the concordant rate of fluorescent in situ hybridization (FISH) with MYB and NFIB immunohistochemistry. Methods: FISH detection of MYB/NFIB gene fusion was performed on 48 head and neck ACC cases and 15 non-ACC salivary gland tumors at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China during April 2014 and January 2020. ACC cases were divided into grade â -â ¡, grade â ¢ and high-grade transformation, according to pathological grading criteria. Prognosis, FISH results and other clinicopathological characteristics were analyzed. MYB and NFIB immunohistochemistry was performed on the 48 ACC and 15 non-ACC cases. The diagnostic accuracy of FISH and immunohistochemistry was compared. Results: FISH detected MYB/NFIB gene fusion in 41.7% (20/48) of the ACC. Its positive rate was inversely correlated with higher pathological grades (P=0.036). The higher histological grade was linked to worse progression-free survival (P=0.024), whereas there was no correlation between the status of gene fusion detected by FISH and progression-free survival (P=0.536). FISH didnot detect MYB/NFIB gene fusion in 15 non-ACC salivary gland tumors The specificity of diagnosing ACC is 100% for both FISH detection of gene fusion and immunohistochemical detection of MYB expression. However, the sensitivity for both methods was only about 41.7%, respectively. By combining FISH and MYB immunohistochemistry, the sensitivity for diagnosing ACC was increased to 66.7%. Conclusions: MYB/NFIB gene fusion has a lower detection rate in grade â ¢ ACC and high-grade transformation ACC. Meanwhile gene fusion status is not correlated with prognosis. The sensitivity for diagnosing ACC can be improved by combining FISH and MYB immunohistochemistry.
Subject(s)
Carcinoma, Adenoid Cystic , Salivary Gland Neoplasms , Humans , Carcinoma, Adenoid Cystic/diagnosis , Carcinoma, Adenoid Cystic/genetics , In Situ Hybridization, Fluorescence , Oncogene Proteins, Fusion/genetics , Salivary Gland Neoplasms/diagnosis , Salivary Gland Neoplasms/genetics , Gene Fusion , Prognosis , NFI Transcription Factors/geneticsABSTRACT
Objective: To summarize the experience of robot-assisted enucleation of tumors located in uncinate process of pancreas. Methods: This is a retrospective case series study. The clinical data of patients with robot-assisted enucleation of tumors located in the uncinate process of pancreas at the Department of Gastroenterology and Pancreatic Surgery,Zhejiang Provincial People's Hospital from June 2019 to December 2023 were retrospectively analyzed. A total of 16 cases were enrolled,including 10 males and 6 females,with an age(M(IQR)) of 56(21)years (range: 28 to 77 years),and body mass index of 22.4(2.3)kg/m2 (range:19.8 to 25.6 kg/m2). Follow-up was asked every 6 to 12 months after the first 3-month postoperative follow-up through out-patient service or via telephone. Results: In total 16 cases,there were 11 cases with pancreatic enucleation,and 5 cases with resection of the uninate process. The operation time was 70(60) minutes (range: 40 to 165 minutes),and the blood loss was 30(13)ml (range: 10 to 80 ml). The rate of pancreatic fistula was 5/16. The length of stay were 8(6)days (range: 5 to 33 days). The pathological finding included non-functional neuroendocrine tumor(n=3),insulinoma(n=2),introductal papillary mucinous neoplasm (n=5),solid pseudopapillary neoplasm (n=2),mucinous cystadenoma (n=1),serous cystadenoma (n=2),pseudocyst (n=1). Follow-up as of March 12, 2024, the follow-up time was 16(12)months (range: 3 to 41 months). All patients had no new onset diabetes and no dyspepsia. Conclusion: Robot-assisted surgical system can be used for local resection of uncinate process tumors of pancreas,and the quality of life of patients can be improved.
ABSTRACT
OBJECTIVES: People living with HIV (PLWH) have a high risk of kidney injury. Measurement of serum creatinine, along with proteinuria, is not sensitive to detect early kidney injury. Here, we investigated novel urinary biomarkers of early renal injury in PLWH. METHODS: We performed a cross-sectional study of 166 antiretroviral-naïve PLWH and 99 HIV-negative persons who all had an estimated glomerular filtration rate > 90 mL/min/1.73 m2 . We compared the levels of seven urinary biomarkers between the two groups using the propensity score matching (PSM) approach and explored the risk factors associated with elevated urinary biomarkers in PLWH. RESULTS: Eighty-three pairs were successfully matched based on PSM. Compared with the HIV-negative group, the HIV-positive group had higher ratios of N-acetyl-ß-D-glucosaminidase (NAG) to urine creatinine (UCr), alpha1-microglobulin (α1-M) to UCr, kidney injury marker-1 (KIM-1) to UCr, neutrophil gelatinase-associated lipocalin to UCr, and epidermal growth factor to UCr, whereas the Tamm-Horsfall protein to UCr ratio and the abnormal albumin to UCr ratio were not significantly different. Positive correlations were observed between HIV RNA level and NAG: UCr (rs = 0.32; P < 0.001) and α1-M:UCr (rs = 0.24; P = 0.002) ratios, and negative correlations were observed between CD4 cell count and NAG:UCr (rs = -0.34; P < 0.001), KIM-1:UCr (rs = -0.16; P = 0.042) and α1-M:UCr (rs = -0.36; P < 0.001) ratios. In multivariate linear regression analyses, older age, lower total cholesterol and higher HIV RNA were independently associated with higher NAG:UCr; older age, lower total cholesterol and lower CD4 cell count were independently associated with higher α1-M:UCr. CONCLUSIONS: In comparioson with HIV-negative participants, PLWH were more likely to have tubular injury. Early antiretroviral treatment might mitigate the development of kidney injury.
Subject(s)
HIV Infections , Biomarkers , China/epidemiology , Cross-Sectional Studies , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/urine , Humans , Kidney , Lipocalin-2ABSTRACT
OBJECTIVES: Tuberculosis (TB) is the most common and fatal opportunistic co-infection among HIV-infected individuals. While TB-associated mortality predominantly occurs in the first 90 days after admission, such a correlation remains unclear in HIV/TB co-infected patients. Thus, we aimed to investigate the 90-day mortality and associated risk factors among HIV/TB co-infected patients in China. METHODS: Adult patients with HIV and a newly confirmed TB diagnosis admitted to the Shanghai Public Health Clinical Center between September 2009 and August 2017 were enrolled. Clinical and laboratory characteristics, key treatments and outcomes were collected retrospectively. The associations between different factors and early mortality were analysed. RESULTS: Of the 485 laboratory-confirmed HIV/TB patients [median (range) age = 39 (19-79) years], 413 (85.15%) were male. Diagnosis was confirmed by culture, pathology and acid-fast bacilli smear alone in 362 (74.6%), 6 (1.2%) and 117 (24.1%) patients, respectively. Multiple drug-/rifampin-resistant TB was detected in 21 (5.8%) of the 367 patients with a positive culture. Rifampin or rifabutin was administered to 402 (82.9%) patients. Additionally, 66 (13.6%) and 86 (17.7%) died within 90 days and 1 year of admission, respectively. Of the 64 TB-related deaths, 59 (92.2%) occurred within 90 days of admission. In Cox regression, central nervous system (CNS) TB [odds ratio (OR) = 2.49, 95% confidence interval (CI): 1.46-4.23, P < 0.001], no antiretroviral therapy (ART) within 3 months after admission (OR = 11, 95% CI: 6.4-18.9, P < 0.001), and plasma albumin level < 25 g/L (OR = 1.91, 95% CI: 1.07-3.40, P = 0.021) were associated with early death. CONCLUSIONS: Tuberculosis co-infection was prevalent and fatal in HIV-infected patients, with most deaths occurring within 90 days of admission. Early mortality was associated with CNS-TB, no ART, and serum albumin level < 25 g/L.
Subject(s)
Antibiotics, Antitubercular/therapeutic use , Coinfection/mortality , HIV Infections/microbiology , Tuberculosis/mortality , Adult , Aged , China/epidemiology , Female , HIV Infections/mortality , Hospitalization , Humans , Male , Middle Aged , Prevalence , Regression Analysis , Retrospective Studies , Rifabutin/therapeutic use , Rifampin/therapeutic use , Risk Factors , Tuberculosis/drug therapy , Young AdultABSTRACT
Objective: To explore the differential protein expressions in papillary thyroid carcinoma (PTC) with or without Hashimoto's thyroiditis (HT). Methods: Tissue microarray was prepared and the protein expression levels of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), vascular endothelial growth factor (VEGF), cyclinD1, mesothelial cell (MC) , CD56 and Galectin3 in the PTC tissues with or without HT were detected by immunohistochemical staining. Results: The positive expression rates of BRAF protein in the PTC tissues with or without HT groups were 55.4% (36/65) and 63.6% (42/66), respectively, without significant difference (P=0.336). The positive expression rates of VEGF protein in the PTC tissues with or without HT groups were 25.7% (19/74) and 25.8%(17/66), respectively, without significant difference (P=0.991). The positive expression rates of cyclin D1 protein in the PTC tissues with or without HT groups were 93.4% (71/76) and 97.6% (80/82), without significant difference (P=0.206). The positive expression rates of MC protein in the PTC tissues with or without HT groups were 86.1% (62/72) and 83.5%(71/85), without significant difference (P=0.654). The positive expression rates of Galectin3 protein in the PTC tissues with or without HT groups were 98.7% (76/77) and 97.5% (78/80), without significant difference (P=0.583). The positive expression rates of CD56 in the PTC tissues and adjacent thyroid follicular epithelial cells were 27.4% (32/117) and 65.0% (76/117), respectively, and the difference was statistically significant (P=0.001). The positive expression rates of CD56 in PTC tissues with or without HT were 35.5% (24/68) and 16.5% (13/79), respectively, and the difference was statistically significant (P=0.009). Conclusions: There are no significant differences in the expressions of BRAF, VEGF, CyclinD1, MC and Galectin3 between the PTC tissues with or without HT. However, the significantly differential expression of CD56 between the two group suggests that CD56 may be related to the pathogenesis of PTC with HT. CD56 may be used as a potential molecular marker in PTC diagnosis.
Subject(s)
Adenocarcinoma, Papillary/genetics , CD56 Antigen/metabolism , Carcinoma, Papillary/pathology , Hashimoto Disease/genetics , Proto-Oncogene Proteins B-raf/genetics , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/pathology , Vascular Endothelial Growth Factor A/metabolism , Adenocarcinoma, Papillary/metabolism , Adenocarcinoma, Papillary/pathology , Animals , Biomarkers/analysis , Carcinoma, Papillary/metabolism , Cyclin D1/genetics , Galectins , Hashimoto Disease/metabolism , Hashimoto Disease/pathology , Humans , Mice , Predictive Value of Tests , Proto-Oncogene Proteins B-raf/metabolism , Thyroid Cancer, Papillary/metabolism , Thyroid Cancer, Papillary/pathology , Thyroid Gland/metabolism , Thyroid Gland/pathology , Thyroid Neoplasms/metabolism , Tissue Array Analysis , Vascular Endothelial Growth Factor A/geneticsABSTRACT
Objective: To analyze the effects of angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) on coronavirus disease 2019 (COVID-19) patients with hypertension, and to provide an evidence for selecting antihypertensive drugs in those patients. Methods: Clinical data were retrospectively analyzed in 58 COVID-19 patients with hypertension admitted to Shanghai Public Health Clinical Center from January 20 to February 22, 2020, including epidemiological history, clinical manifestations, laboratory findings, chest CT and outcome. Patients were divided into ACEI/ARB group and non-ACEI/ARB group. Results: Twenty-six patients were in ACEI/ARB group and the other 32 patients in non-ACEI/ARB group, with median age 64.0 (49.5, 72.0) years and 64.0 (57.0, 68.8) years respectively. The median time to onset was 5(3, 8) days in ACEI/ARB group and 4 (3, 7) days in non-ACEI/ARB group, the proportion of patients with severe or critical illness was 19.2% and 15.6% respectively. The main clinical symptoms in two groups were fever (80.8% vs. 84.4%) and cough (23.1% vs. 31.3%). The following parameters were comparable including lymphocyte counts, C-reactive protein, lactate dehydrogenase, D-dimer, bilateral involvement in chest CT (76.9% vs. 71.9%), worsening of COVID-19 (15.4% vs. 9.4%), favorable outcome (92.3% vs. 96.9%) between ACEI/ARB group and non-ACEI/ARB group respectively (all P>0.05). However, compared with non-ACEI/ARB group, serum creatinine [80.49 (68.72, 95.30) µmol/L vs. 71.29 (50.98, 76.98) µmol/L, P=0.007] was higher significantly in ACEI/ARB group. Conclusions: ACEI/ARB drugs have no significant effects on baseline clinical parameters (serum creatine and myoglobin excluded) , outcome, and prognosis of COVID-19 patients with hypertension. Antihypertensive drugs are not suggested to adjust in those patients, but the potential impairment of renal function as elevation of serum creatinine should be paid attention in patients administrating ACEI/ARB drugs.
Subject(s)
Betacoronavirus , Coronavirus Infections , Hypertension , Pandemics , Pneumonia, Viral , Aged , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , COVID-19 , China , Coronavirus Infections/complications , Humans , Hypertension/complications , Middle Aged , Pneumonia, Viral/complications , Retrospective Studies , SARS-CoV-2ABSTRACT
Objective: To summarize the clinical characteristics and liver biochemical parameters of 324 cases admitted with novel coronavirus pneumonia in Shanghai area. Methods: Clinical data and baseline liver biochemical parameters of 324 cases with novel coronavirus pneumonia admitted to the Shanghai Public Health Clinical Center from January 20, 2020 to February 24, 2020 were retrospectively analyzed. Patients were divided into two groups based on the status of illness: mild type (mild and typical) and severe type (severe and critical).The differences in clinical data and baseline liver biochemical parameters of the two groups were described and compared. The t-test and Wilcoxon rank-sum test were used for measurement data. The enumeration data were expressed by frequency and rate, and chi-square test was used. Results: Of the 324 cases with novel coronavirus pneumonia, 26 were severe cases (8%), with median onset of 5 days, 20 cases were HBsAg positive (6.2%), and 70 cases (21.6%) with fatty liver, diagnosed with X-ray computed tomography. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bilirubin (TBil), albumin(ALB) and international normalized ratio (INR) of 324 cases at baseline were 27.86 ± 20.02 U/L, 29.33 ± 21.02 U/L, 59.93 ± 18.96 U / L, 39.00 ± 54.44 U/L, 9.46 ± 4.58 µmol / L, 40.64 ± 4.13 g / L and 1.02 ± 0.10. Of which, ALT was > than the upper limit of normal (> ULN), accounting for 15.7% (51/324). ALT and AST > ULN, accounting for 10.5% (34/324). ALP > ULN, accounting for 1.2% (4/324). ALP and GGT > ULN, accounting for 0.9% (3/324). INR > ULN was lowest, accounting for 0.6% (2/324). There were no statistically significant differences (P > 0.05) in ALT [(21.5 vs. 26) U / L, P = 0.093], ALP [(57 vs.59) U/L, P = 0.674], and GGT [(24 vs.28) U/L, P = 0.101] between the severe group and the mild group. There were statistically significant differences in AST (23 U/L vs. 34 U/L, P < 0.01), TBil (10.75 vs. 8.05 µmol / L, P < 0.01), ALB (35.79 ± 4.75 vs. 41.07 ± 3.80 g/L, P < 0.01), and INR (1.00 vs. 1.04, P < 0.01). Conclusion: The baseline liver biochemical parameters of 324 cases with novel coronavirus pneumonia in Shanghai area was comparatively lower and the liverinjury degree was mild, and the bile duct cell damage was rare.
Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Alanine Transaminase , Aspartate Aminotransferases , COVID-19 , China , Humans , Liver , Retrospective Studies , SARS-CoV-2ABSTRACT
1. The objectives of the current study were to investigate the mitochondrial genome and molecular phylogeny of Lueyang black-bone chicken, and provide molecule base to preserve and explore the specific chicken strain. 2. Based on sequencing and clustering, the complete mitochondrial DNA map and sequences of Lueyang black-bone chicken were revealed, and two phylogenetic trees of Lueyang black-bone chickens based on D-loop sequences and the mitochondrial genome were constructed. 3. The results showed that the complete mitochondrial genome of Lueyang black-bone chickens is 16,784bp in size, consisting of 22 transfer RNA genes, two ribosomal RNA genes, 13 protein-coding genes, and one non-coding control region. The base composition of the complete mtDNA sequence is 30.28% for A, 23.78% for T, 32.42% for C, 13.52% for G. Additionally, 10 haplotypes of D-loop sequences in 32 Lueyang black-bone chickens were detected, which were distributed into 4 clades (A, B, C and E). 4. It was concluded that genetic diversity is wide in Lueyang black-bone chickens, and this strain has multiple maternal origins from different regions in China and neighbouring regions.
Subject(s)
Chickens/genetics , DNA, Mitochondrial/genetics , Genome, Mitochondrial/genetics , Phylogeny , Animals , DNA, Mitochondrial/chemistry , Genetic Variation/genetics , Haplotypes/genetics , Polymerase Chain Reaction/veterinary , Sequence Analysis, DNA , Species SpecificityABSTRACT
Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease. As a dengue non-endemic country, China has experienced several dengue outbreaks in recent years. However, dengue patients in China displayed distinct clinical characteristics compared to patients in endemic countries. To standardize the diagnosis and treatment of dengue fever, the experts of the Society of Infectious Diseases, Society of Tropical Medicine and Parasitology of Chinese Medical Association, and the Society of Emergency Medicine, China Association of Chinese Medicine have reached this guideline based on guidelines for diagnosis, treatment, prevention and control of dengue (World Health Organization, 2009); guidelines for diagnosis and treatment of dengue (National Health and Family Planning Commission of the People's Republic of China, 2014, Edition 2), health industry standard of the People's Republic of China "diagnosis for dengue fever (WS216-2018)" and systemic reports on dengue. The guideline includes 8 aspects: introduction, terminology, epidemiology and prevention, etiology and pathogenesis, clinical features, diagnosis, treatment and problems to be solved.
Subject(s)
Dengue/diagnosis , Dengue/drug therapy , Disease Outbreaks/prevention & control , Practice Guidelines as Topic , China , Humans , World Health OrganizationABSTRACT
Cryptococcal meningitis is a common and refractory central nervous system infection, with high rates of mortality and disability. The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion. Based on the current situation of cryptococcal meningitis in China, the management of cryptococcal meningitis includes 6 aspects: introduction, microorganism identification, clinical manifestations and diagnosis, principles of antifungal therapy, treatment of refractory and recurrent meningitis, treatment of intracranial hypertension. There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis. This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines. The importance of early diagnosis, combined long-term antifungal therapy, control of intracranial hypertension are emphasized.
Subject(s)
Consensus , Intracranial Hypertension/etiology , Meningitis, Cryptococcal/diagnosis , Adult , Antifungal Agents/therapeutic use , China , Humans , Intracranial Hypertension/parasitology , Male , Meningitis, Cryptococcal/drug therapyABSTRACT
A total of 48 carcasses of crossbred Hanzhong White pigs were divided into 3 groups (I, 90-99 kg; II, 100-109 kg; III, 110-119 kg) to investigate the influence of carcass weight on meat quality. The intramuscular fat content of the 3 groups increased from 1.90 to 4.90%; for meat color, Warner-Bratzler shear force, drip loss, and oxidation-type muscle fiber percentage, and muscle fiber diameter of the longissimus lumborum, the indices in group II and group III were better than those in group I (P < 0.05). The saturated fatty acid and polyunsaturated fatty acid percentages of the longissimus lumborum muscle (2.80 and 37.30%, respectively) in group II were significantly lower than those in the other 2 groups, while the monounsaturated fatty acid percentage was the highest (59.10%). In conclusion, our results suggest that a carcass weight of 100-109 kg is sufficient to produce acceptable meat quality of Hanzhong White pigs.
Subject(s)
Body Weight , Meat/standards , Muscle, Skeletal/cytology , Adipose Tissue/metabolism , Animals , Body Composition , Muscle, Skeletal/chemistry , SwineABSTRACT
Objective: To evaluate the efficacy and safety of pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC). Methods: This was a prospective, single-arm, open label, phase 2 clinical study enrolling patients at the Cancer Hospital of the Chinese Academy of Medical Sciences with R/M HNSCC treated with pembrolizumab plus nab-paclitaxel and cisplatin or carboplatin. After six cycles of treatment, patients received pembrolizumab as maintenance therapy until disease progression or intolerable toxicity or completion of 35 cycles of treatment. The primary endpoint was objective response rate, and secondary endpoints included overall survival, progression-free survival, and safety profile. Efficacy was evaluated according to the response evaluation criteria in solid tumors 1.1, survival analysis was performed using the Kaplan-Meier method, and adverse events were assessed using the America National Cancer Institute Common Terminology Criteria for Adverse Events 5.0. Results: A total of 30 patients with R/M HNSCC were enrolled from 23 April 2021 to 22 March 2023, including 28 males and 2 females, with a median age of 67 years. The median follow-up time was 14.5 months, the objective response rate was 70.0%, the disease control rate was 96.7%, and the median progression-free survival and overall survival of all patients were 11.6 months and 18.8 months, respectively. Median duration of response was up to 17.3 months. Grade≥3 treatment-related adverse events were leukopenia (26.7%), neutropenia (26.7%), peripheral neurotoxicity (3.3%), rash (3.3%), hyperalgesia (3.3%), and immune-related pneumonitis (3.3%). The most common immune-related adverse event was hypothyroidism (40.0%). Conclusion: Pembrolizumab combined with nab-paclitaxel and platinum shows encouraging antitumor activity accompanied with a manageable safety profile in untreated R/M HNSCC patients in China.
Subject(s)
Albumins , Antibodies, Monoclonal, Humanized , Head and Neck Neoplasms , Platinum , Male , Female , Humans , Aged , Squamous Cell Carcinoma of Head and Neck/drug therapy , Prospective Studies , Paclitaxel/therapeutic use , Head and Neck Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Objective: To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients. Methods: This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy. Results: By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage â ¢ and 20 patients in stage â £. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence. Conclusions: The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.
Subject(s)
Head and Neck Neoplasms , Neoadjuvant Therapy , Male , Humans , Female , Squamous Cell Carcinoma of Head and Neck , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , ImmunotherapyABSTRACT
OBJECTIVES: The aim of the study was to determine the seroprevalence and epidemiological features of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among patients newly diagnosed with HIV/AIDS in China. METHODS: Two thousand and forty patients newly diagnosed with HIV/AIDS from 10 provinces in China were selected during 2009 to 2010. Serum samples obtained from each individual were screened for HBV and HCV serum markers [HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), HBV envelope antigen (HBeAg), HBV envelope antibody (HBeAb), HBV core antibody (HBcAb) and HCV antibody (HCVAb)]; liver function tests were also performed. Demographics and medical histories were collected. RESULTS: Of the 2040 patients, 741 (36.3%) were positive for at least one HBV and HCV serum marker; 300 (14.71%) were HCVAb positive, and 248 (12.16%) were isolated HCVAb positive; 222 (10.9%) were positive for HBsAg; 19 (0.93%) were positive for both HBsAg and HCVAb. The highest prevalence of HBsAg positivity was found in Guangxi (15.31%), followed by Guangdong (15.19%) and Shanghai (14.36%). The highest prevalence of HCVAb positivity was found in Xinjiang (43.18%), followed by Henan (39.06%) and Yunnan (27.36%). The proportion of patients with abnormal liver function in patients positive for HCVAb and/or HBsAg was significantly higher than that in those who were negative for both HCVAb and HBsAg (P < 0.001). CONCLUSIONS: The seroprevalence of HBV and HCV among patients newly diagnosed with HIV/AIDS in China is high. HBsAg and HCVAb positivity prevalences were found to vary significantly in different provinces in China. Patients newly diagnosed with HIV/AIDS and coinfected with HBV and HCV are at higher risk of abnormal liver function. It is necessary to routinely screen for HBV and HCV infection among patients newly diagnosed with HIV/AIDS.
Subject(s)
Acquired Immunodeficiency Syndrome/blood , DNA, Viral/blood , HIV Seropositivity/blood , Hepatitis B, Chronic/blood , Hepatitis C, Chronic/blood , Liver Function Tests/methods , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/virology , Adult , Biomarkers/blood , China/epidemiology , Female , HIV Seropositivity/epidemiology , HIV Seropositivity/virology , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/virology , Hepatitis C Antibodies/blood , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , Prevalence , Seroepidemiologic StudiesABSTRACT
Airway smooth muscle (ASM) cell phenotype modulation, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to proliferative diseases such as allergic asthma and chronic obstructive pulmonary disease (COPD). KCa3.1 has been suggested to be involved in regulating ASM cell activation, proliferation, and migration. However, little is known regarding the exact role of KCa3.1 in ASM cell phenotypic modulation. To elucidate the role of KCa3.1 in regulating ASM cell phenotypic modulation, we investigated the effects of KCa3.1 channels on ASM contractile marker protein expression, proliferation and migration of primary human bronchial smooth muscle (BSM) cells. We found that PDGF increased KCa3.1 channel expression in BSM cells with a concomitant marked decrease in the expression of contractile phenotypic marker proteins including smooth muscle myosin heavy chain (SMMHC), smooth muscle α-actin (α-SMA), myocardin and KCa1.1. These changes were significantly attenuated by the KCa3.1 blocker, TRAM-34, or gene silencing of KCa3.1. Pharmacological blockade or gene silencing of KCa3.1 also suppressed PDGF-induced human BSM cell migration and proliferation accompanied by a decrease in intracellular free Ca(2+) levels as a consequence of membrane depolarization, resulting in a reduction in cyclin D1 level and cell cycle arrest at G0-G1 phase. Additionally, PDGF-induced up-regulation of KCa3.1 and down-regulation of BSM contractile marker proteins were regulated by the ERK inhibitor U0126 and the AKT inhibitor LY294002. These findings highlight a novel role for the KCa3.1 channel in human BSM cell phenotypic modulation and provide a potential target for therapeutic intervention for proliferative airway diseases.
Subject(s)
Intermediate-Conductance Calcium-Activated Potassium Channels/biosynthesis , Intermediate-Conductance Calcium-Activated Potassium Channels/physiology , Myocytes, Smooth Muscle/physiology , Phenotype , Up-Regulation , Actins/biosynthesis , Bronchi/drug effects , Bronchi/metabolism , Bronchi/physiology , Butadienes/pharmacology , Calcium/metabolism , Cell Cycle Checkpoints/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Chromones/pharmacology , Cyclin D1/metabolism , Down-Regulation/drug effects , Down-Regulation/physiology , Gene Silencing , Humans , Intermediate-Conductance Calcium-Activated Potassium Channels/antagonists & inhibitors , Intermediate-Conductance Calcium-Activated Potassium Channels/genetics , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/biosynthesis , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/genetics , Morpholines/pharmacology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Myosin Heavy Chains/biosynthesis , Nitriles/pharmacology , Nuclear Proteins/biosynthesis , Platelet-Derived Growth Factor/antagonists & inhibitors , Platelet-Derived Growth Factor/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrazoles/pharmacology , Trans-Activators/biosynthesis , Up-Regulation/drug effectsABSTRACT
Beta-type titanium alloys are excellent candidates for biomedical applications because of their very low elastic modulus, excellent corrosion resistance, and biocompatibility. However, many traditional ß-type titanium alloys exhibit low yield strength. In this study, a small amount of Si (3 and 5 at.%) was added to a Ti-35Nb-7Zr-5Ta (wt%, TNZT) biomedical alloy prepared via laser powder bed fusion (LPBF) to increase its yield strength. The Si addition resulted in a significant increase in the compression yield strength of the alloy (from 802 to 1282 MPa). Meanwhile, the elastic moduli of the TNZT alloys (48.7-60.6 GPa) with 3 and 5 at.% Si were much lower than that of the Ti-6Al-4 V alloy (110 GPa), which is used extensively in clinical applications. The microstructural analyses indicated that the ultrahigh-strength of the TNZT alloy containing Si was due to the presence of ultrafine (Ti, Nb, Zr)5Si3 (S1) grains in the ß-Ti matrix. In addition, thin shell-shaped S1 and (Ti, Nb, Zr)2Si (S2) grains precipitated along the columnar ß-Ti grain boundaries in the TNZT alloys containing 3 and 5 at.% Si, respectively. Moreover, the introduction of Si to the TNZT alloy significantly refined the grains, weakened the cubic texture, decreased surface roughness, and improved Vickers hardness. The ultrahigh strength of the Si-containing TNZT alloys was due to grain boundary strengthening and precipitation strengthening. In addition, in vitro studies with MC3T3-E1 cells revealed that the cytocompatibilities of the LPBF-fabricated TNZT and Si-containing TNZT alloys were equivalent and were better than that of the LPBF-fabricated Ti-6Al-4 V alloy. In particular, the TNZT alloy with 3 at.% Si showed the best elastic modulus (48.7 ± 1.0 GPa), yield strength (1151 ± 17 MPa), and cell biological response among all the alloys investigated in this study, and hence was found to be a suitable candidate for application in load-bearing bone implants.
Subject(s)
Alloys , Titanium , Alloys/chemistry , Lasers , Powders , Silicon , Titanium/chemistryABSTRACT
The objective of this study was to evaluate the efficacy and safety of pegylated interferon (PEG-IFN) alpha-2a monotherapy in a cohort of Chinese haemophilic patients co-infected with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) and undergoing highly active antiretroviral drugs therapy. Twenty-two (n = 22) patients with CD4 lymphocyte counts over 200 cells microL(-1) were treated with 180 microg of PEG-IFN alpha-2a subcutaneously once in a week for 48 weeks. HCV load (HCV RNA), HIV load (HIV RNA) and CD4 lymphocyte counts were measured at baseline and 4, 12, 24, 48 and 72 weeks after initiation of anti-HCV therapy. Efficacy and safety were analysed according to baseline CD4 status (> or =350 cells microL(-1)). Significant HCV-RNA decreases (>1 log(10) copies mL(-1)) were observed through week 72 after PEG-INF alpha-2a monotherapy across both CD4 strata. CD4 status was not associated with treatment outcomes as evaluated using rapid viral response rate (P = 0.655), early viral response rate (P = 0.387), end-of-treatment viral response rate (P = 1.000) or sustained viral response rate (SVR, P = 0.674). A sustained virological response was achieved in nine patients (41%), five with genotype 2a (83%) and four with genotype 1b (25%, P = 0.023). SVR was HCV genotype dependent. Eleven patients required a dose reduction in PEG-IFN alpha-2a. PEG-IFN alpha-2a monotherapy could be considered as a safe and effective option for the treatment of HCV infection in HIV patients with haemophilia, particularly in resource-limited settings. While higher CD4 lymphocyte counts resulted in greater HCV-RNA reduction, HCV genotype was a predictor for sustained virological response.
Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/complications , Hemophilia A/complications , Hepatitis C/complications , Hepatitis C/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Antiviral Agents/adverse effects , China , Cohort Studies , Genotype , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Male , Polyethylene Glycols/adverse effects , RNA, Viral/analysis , Recombinant Proteins , Viral LoadABSTRACT
Small axial-flow fans used for computer cooling and many other appliances feature a rotor driven by a downstream motor held by several cylindrical struts. This study focuses on the aerodynamic mechanism of rotor-strut interaction for an isolated fan. The three-dimensional, unsteady flow field is calculated using FLUENT, and the sound radiation predicted by acoustic analogy is compared with measurement data. Striking differences are found between the pressure oscillations in various parts of the structural surfaces during an interaction event. The suction surface of the blade experiences a sudden increase in pressure when the blade trailing edge sweeps past a strut, while the process of pressure decrease on the pressure side of the blade is rather gradual during the interaction. The contribution of the latter towards the total thrust force on the structure is cancelled out significantly by that on the strut. In terms of the acoustic contributions from the rotor and strut, the upstream rotor dominates and this feature differs from the usual rotor-stator interaction acoustics in which the downstream part is responsible for most of the noise. It is therefore argued that the dominant interaction mechanism is potential flow in nature.