[Clinical characteristics of 42 patients with different subspecies of Mycobacterium abscessus complex pulmonary disease].

Objective: To compare clinical features and treatment outcomes of Mycobacterium abscessus (M.abscessus) and Mycobacterium massiliense (M.massiliense) pulmonary disease. Methods: A retrospective analysis was performed for 42 patients diagnosed with M.abscessus complex pulmonary disease for the first time in Guangzhou Chest Hospital from January to September 2021. The age of the 42 patients was 17-73 years, including 15 males and 27 females. According to the targeted next-generation sequencing, the patients were divided into M.abscessus group (28 patients, including 10 males and 18 females) and M. massiliense group (14 patients, including 5 males and 9 females). The clinical characteristics, radiological findings, drug sensitivity and clinical efficacy evaluation at 6 months of the two groups were compared. χ2 test and t-test were used for comparison between two groups. Results: The main symptoms in M. abscessus and M. massiliense groups were cough and sputum production. Radiological findings were significantly more frequent in the M. abscessus group than in the M. massiliense group, tree-in-bud sign [22/28 (78.5%) vs. 5/14], nodular bronchiectasis [27/28 (96.4%) vs. 11/14], and lesions involving more than three lung fields [23/28 (82.1%) vs. 7/14]. Both groups showed high levels of resistance to all antimicrobials. The sensitivity rate of the M. massiliense group to clarithromycin was higher than that of the M. abscessus[13/14 vs. 15/28 (53.5%)], and the success rate of treatment was significantly higher in patients with M. massiliense at the 6-month efficacy evaluation. Conclusions: The radiological findings, drug sensitivity and treatment outcomes differ between M. abscessus and M. massiliense pulmonary disease. Improving the identification of bacterial subspecies in clinical practice can effectively improve the diagnosis and treatment.

Effects of RAD51-stimulatory compound 1 (RS-1) and its vehicle, DMSO, on pig embryo culture.

Pigs have become an important model for agricultural and biomedical purposes. The advent of genomic engineering tools, such as the CRISPR/Cas9 system, has facilitated the production of livestock models with desired modifications. However, precise site-specific modifications in pigs through the homology-directed repair (HDR) pathway remains a challenge. In mammalian embryos, the use of small molecules to inhibit non-homologous end joining (NHEJ) or to improve HDR have been tested, but little is known about their toxicity. The compound RS-1 stimulates the activity of the RAD51 protein, which plays a key role in the HDR mechanism, demonstrating enhancement of HDR events in rabbit and bovine zygotes. Thus, in this study, we evaluated the dosage and temporal effects of RS-1 on porcine embryo development and viability. Additionally, we assessed the effects of its vehicle, DMSO, during embryo in vitro culture. Transient exposure to 7.5 µM of RS-1 did not adversely affect early embryo development and was compatible with subsequent development to term. Additionally, low concentrations of its vehicle, DMSO, did not show any toxicity to in vitro produced embryos. The transient use of RS-1 at 7.5 µM during in vitro culture seems to be the best protocol of choice to reduce the potentially toxic effects of RS-1 while attempting to improve HDR in the pig. Direct injection of the CRISPR/Cas9 system, combined with strategies to increase the frequency of targeted modifications via HDR, have become an important tool to simplify and accelerate the production of genetically modified livestock models.

[The clinical characteristics of 89 cases of non-tuberculous mycobacterium pulmonary disease complicated with tracheobronchial lesions].

Objective: To explore the clinical characteristics of non-tuberculous mycobacterium(NTM) pulmonary disease complicated with tracheobronchial lesions. Methods: From January 2014 to December 2018, there were 1 006 patients who were admitted to Guangzhou Chest Hospital for the first time and received examination by bronchoscopy. A total of 89 patients with complete data were selected, including 40 males and 49 females, aged 20 to 85 years, with 46 patients (52%) aged 60 years or older. The clinical symptoms and signs of the patients were analyzed with chest imaging, bronchoscopy and pathological examination results. Comparisons between groups were made by Chi-square test and t test. Results: The number of patients with NTM complicated with tracheobronchial lesions accounted for 8.9%(89/1 006) of those hospitalized with NTM and received bronchoscopy during the same period. Clinical symptoms included cough and sputum (89/89), different degrees of hemoptysis or blood sputum (52/89), and shortness of breath (50/89). Chest CT showed that 72 cases (72/89, 81%) had lung lesions involving more than 3 lung fields, and 83 cases (93%) had bronchiectasis and 63 cases (63/89, 71%) with cavities. Pulmonary atelectasis was shown in 45 cases (45/89, 51%). By bronchoscopy, 39 cases (39/89, 44%) were diagnosed as tuberculous lesions involving bilateral upper bronchi, while lesions of the right lower bronchus was found in 27 cases (27/89, 30%).The percentage of patients with multilobar bronchial involvement was 50.6%(45/89). The morphological characteristics of the bronchial lesions included scar stenosis or atresia in 63 cases (63/89, 71%), hyperemia and edema in 46 cases (46/89, 52%), and multiple types of lesions in 48 cases (48/89, 54%). Conclusions: Patients with NTM lung disease complicated with tracheobronchial inflammatory lesions did not have specific manifestations clinically. Lung lesions are extensive, often accompanied by bronchiectasis and cavity formation. Endoscopic changes were mostly manifested as multilobar tracheobronchial involvement characterized by scar stenosis, congestion and edema, mainly involving bilateral upper bronchi and the right lower bronchus.

Impacts of treatments on the quality of life among esophageal squamous cell carcinoma patients.

This study aims to investigate the effects of treatments on the quality of life for patients with esophageal squamous cell carcinoma patients diagnosed at early and late stages. From a medical center in central Taiwan, patients who had been diagnosed with esophageal squamous cell carcinoma from February 2007 and March 2011 were recruited. Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Quality of Life Questionnaire Oesophageal 18 (QLQ-OES18), quality of life scores for 105 esophageal squamous cell carcinoma patients were obtained and assessed. Multivariate analysis was performed on the quality of life scores after stratification by cancer stage. Among early-stage esophageal squamous cell carcinoma patients, those received only surgery (S-only) performed better in physical and social functioning compared with patients who underwent surgery and concurrent chemoradiotherapy (S+CCRT) (ß = 9.0, P = 0.03; ß = 12.1, P = 0.04, respectively). For those that received only concurrent chemoradiotherapy (CCRT-only), they performed worse in role and emotional functioning relative to S+CCRT patients (ß = -17.2, P = 0.02; ß = -15.7, P = 0.05, respectively). Among late-stage patients, CCRT-only treatment gave insignificantly better global health status and functional scale scores and less severe symptoms compared to the S+CCRT option. Better functional scores and less aggravated symptoms are observed in early-stage esophageal squamous cell carcinoma patients who received surgery-only treatment relative to those that underwent both surgery and chemoradiotherapy. For late-stage esophageal cancer patients, the measured difference of quality of life is not significant between CCRT-only and S+CCRT treatments.

Association between radical prostatectomy and risk of herpes zoster.

The present study investigated the association between radical prostatectomy (RP) and the risk of herpes zoster (HZ). Male patients aged ≥ 40 years and diagnosed with prostate cancer (PCa) between 2000 and 2005 were included in this study. Patients who underwent RP for the first time during 2000-2006 were included in the RP group. Randomly selected individuals from among the remaining patients with PCa who did not undergo RP were included in the non-RP group. Univariate and multivariate Cox regression models were used to analyze the association between PCa and HZ. In addition, the association between RP and the risk of HZ in different subgroups was evaluated after stratification by age, comorbidities, and hormone therapy (HoT) status. Furthermore, the combined effect of RP and HoT on the risk of HZ was evaluated. This study included 1,380 patients with PCa who newly underwent RP and 1,371 patients with PCa who did not undergo RP. During follow-up, 96 and 104 patients in the RP and non-RP groups, respectively, developed HZ. Patients who underwent both RP and HoT showed a significantly reduced risk of HZ, compared with patients who did not undergo both RP and HoT. RP is not associated with an increased risk of HZ. However, prostate-specific antigen levels should be monitored routinely during follow-up to detect PCa recurrence.

INVITED REVIEW: Inhibitors of myostatin as methods of enhancing muscle growth and development.

With the increasing demand for affordable, high-quality meat, livestock and poultry producers must continually find ways to maximize muscle growth in their animals without compromising palatability of the meat products. Muscle mass relies on myoblast proliferation during prenatal or prehatch stages and fiber hypertrophy through protein synthesis and nuclei donation by satellite cells after birth or hatch. Therefore, understanding the cellular and molecular mechanisms of myogenesis and muscle development is of great interest. Myostatin is a well-known negative regulator of muscle growth and development that inhibits proliferation and differentiation in myogenic cells as well as protein synthesis in existing muscle fibers. In this review, various inhibitors of myostatin activity or signaling are examined that may be used in animal agriculture for enhancing muscle growth. Myostatin inhibitors are relevant as potential therapies for muscle-wasting diseases and muscle weakness in humans and animals. Currently, there are no commercial myostatin inhibitors for agriculture or biomedical purposes because the safest and most effective option has yet to be identified. Further investigation of myostatin inhibitors and administration strategies may revolutionize animal production and the medical field.

Mild heat stress enhances differentiation and proliferation of Japanese quail myoblasts and enhances slow muscle fiber characteristics.

The objective of this study was to investigate the effect of mild heat stress on muscle fiber hyperplastic and hypertrophic growth in quail primary myogenic cells to better understand the mechanisms leading to increased skeletal muscle development in avian embryos incubated at a higher temperature. Compared to control cultures maintained at 37°C, incubation at 39°C enhanced myotube length (P < 0.01) and diameter (P < 0.001) at 3 days after differentiation (D3). This enlargement of the myotubes incubated at 39°C can be explained by differences in the fusion index (56.7 vs. 46.2%, P < 0.05) and nuclei number per myotube (18.1 vs. 10.8, P < 0.001) compared to the control cells at D3. Additionally, a higher density of myotubes at D3 in cultures exposed to a higher temperature were related to higher levels of Pax-7 (P < 0.05) compared to the control cells incubated continuously at 37°C. These results indicated a higher proliferative capacity in cells exposed to mild heat stress compared to the control cells. On the other hand, mild heat stress enhanced protein levels of slow myosin heavy chain isoform (P < 0.01) and cytochrome c oxidase subunit IV (P < 0.01) compared to the control cells at D3. These discrepancies in protein expression indicated maintenance of slow muscle fiber type characteristics in myotubes incubated at 39°C. Our results suggest that mild heat stress plays a significant role in myogenic mechanisms related to muscle mass and development.

Differential Expression of Cell Cycle Regulators During Hyperplastic and Hypertrophic Growth of Broiler Subcutaneous Adipose Tissue.

Hyperplastic growth and hypertrophic growth within adipose tissue is tightly associated with cell cycle activity. In this study, CCNG2 and CDKN2C were found to be correlated with cell cycle inhibition during fat cell differentiation, whereas CCND3, CCNA1, and ANAPC5 were positively associated with cell cycle activity during fat cell proliferation after selection based on GEO datasets available on the NCBI website. The findings were validated through comparison of expressions of these genes among different tissues/fractions in broiler chickens and time points during primary cell culture using quantitative real-time PCR. Development of broiler subcutaneous adipose tissue was investigated on embryonic days 15 and 17 and on post-hatch days 0, 5, 11, and 33 using H&E staining and PCNA immunostaining with DAPI counter stain. In addition, mRNA expressions of five cell cycle regulators as well as precursor cell and adipocyte markers were measured at those time points. The results suggest that cellular proliferation activity decreased as the fat pad grows, but a population of precursor cells seemed to be maintained until post-hatch day 5 despite increasing differentiation activity. Hypertrophic growth gradually intensified despite a slight cessation on post-hatch day 0 due to increased energy expenditure during hatching and delayed food access. From post-hatch day 5 to day 11, most of the precursor cells may become differentiated. After post-hatch day 11, hyperplastic growth seemed to slow, while hypertrophic growth may become dominant. This study provides further understanding about broiler fat tissue development which is imperative for effective control of fat deposition.

Safety of high doses of urokinase and reteplase for acute ischemic stroke.

BACKGROUND AND PURPOSE: ET is considered in selected patients with AIS with persistent arterial occlusion after receiving IVT. Limited data exist on the safety of IA high doses of UK and RT for ET. We investigated any correlation between IA doses of UK or RT and safety outcomes in patients who underwent ET. MATERIALS AND METHODS: We identified all patients from our stroke registry who received UK or RT for ET from 1998 to 2008. Demographics, baseline National Institutes of Health Stroke Scale scores, recanalization rates, rates of attempted MT, mortality, SICH, and discharge modified Rankin Scale scores were collected. RESULTS: Of 197 patients; 72 received UK and 125 received RT. More than 90% of patients in both groups had received prior IVT. The median IA dose of UK was 200,000 U (range, 25,000-1,500,000 U) and of RT was 2 mg (range, 1-8 mg). Concurrent MT was attempted in 59.7% of UK-treated patients and 72.0% of RT-treated patients, with SICH rates of 4.2% and 8.0%, respectively. Logistic regression adjusting for prior IVT and MT revealed no correlation between SICH and doses of UK (OR, 1.00; 95% CI, 0.99-1.00; P = .94) or RT (OR, 0.803; 95% CI, 0.48-1.33; P = .39). There was no correlation between mortality and doses of UK (OR, 1.00; 95% CI, 0.99-1.00; P = .51) or RT (OR, 1.048; 95% CI, 0.77-1.42; P = .75). CONCLUSIONS: High IA doses of UK and RT may be safe when given with or without MT in patients with AIS despite receiving a full dose of intravenous recombinant tissue plasminogen activator. These results need prospective validation.

Validation of multi-channel auditory steady-state response in adults with sensorineural hearing loss.

OBJECTIVE: For various medico-legal and financial reasons, some patients may clinically demonstrate an exaggerated hearing loss that varies in degree, nature and laterality. The purpose of this study was to evaluate whether multi-channel auditory steady-state response measurement can be used as an objective test of auditory thresholds in adults with sensorineural hearing loss. STUDY DESIGN AND SETTING: This was a prospective, comparative, experimental research design study conducted in an academic medical centre. From January to June 2007, 142 subjects (284 ears) with varying degrees of sensorineural hearing loss were included. Four commonly used frequencies (500, 1000, 2000 and 4000 Hz) were evaluated. Both pure tone thresholds and multi-channel auditory steady-state response thresholds were obtained for each ear in all subjects. The correlation of auditory steady-state response thresholds and pure tone thresholds was assessed. The time taken for multi-channel auditory steady-state response testing was also recorded. RESULTS: Results for multi-channel auditory steady-state response thresholds and pure tone thresholds were compared for each test frequency. A difference of less than 15 dB was found in 71 per cent of patients, while a difference of less than 20 dB was found in 83 per cent. Correlation between auditory steady-state response thresholds and pure tone thresholds, expressed as the correlation coefficient (r), was 0.89, 0.95, 0.96 and 0.97 at 500, 1000, 2000 and 4000 Hz, respectively. The strength of the relationship between auditory steady-state response thresholds and pure tone thresholds increased with increasing frequency and increasing degree of hearing loss. The recorded auditory steady-state response thresholds were used to calculate regression lines predicting pure tone threshold results. The mean estimated pure tone thresholds calculated from these regression lines were all within 10 dB of the actual recorded pure tone thresholds. The average multi-channel auditory steady-state response test duration was 42 minutes per patient. CONCLUSION: Measurement of multi-channel auditory steady-state response could be a powerful, convenient electro-physiological examination with which to objectively certify clinical hearing impairment in adults.

Persistent lower abdominal pain induced by long peritoneal shunt catheter.

Persistent abdominal pain directly induced by a peritoneal catheter of a ventriculoperitoneal shunt, which is associated with no other complications such as bowel perforation, pseudocyst or infection, has not been previously reported. A 65-year-old woman with hydrocephalus developed persistent lower abdominal pain radiating to the perineal area after shunt insertion. Radiography suggested that the distal end of a peritoneal catheter was located in a cul-de-sac of the pelvis. Otherwise, all studies were negative for shunt infection, fluid collection, or other abdominal and pelvic events. The patient's pain resolved completely after surgery in which the peritoneal catheter was shortened. In the presence of unexplained, persistent lower abdominal pain after shunt placement, the need to shorten the peritoneal catheter should be considered.

Bipaddled radial forearm flap for the reconstruction of bilateral buccal defects in oral submucous fibrosis.

Oral submucous fibrosis can result in progressive closure of the mouth. A total of 10 patients with advanced oral submucous fibrosis were surgically treated. The procedure consisted of (1) release of all the intraoral fibrotic tissue, (2) masticatory muscle myotomy and coronoidotomy, and (3) reconstruction with a bipaddled radial forearm flap. Preoperative mouth opening was 0-5mm (mean 2.3mm). The intraoperative mouth opening was 12-20mm (mean 16 mm) after submucous release, and 32-42 mm (mean 35.5mm) after further release via myotomy and coronoidotomy. The proximal flap included one perforator in four patients and two perforators in the remaining six patients. The flaps were 8-9 cm in length and 2-2.5 cm in width. Nine flaps survived uneventfully. Arterial thrombosis was noted in one flap, which was successfully salvaged. Temporomandibular joint subluxation developed in one patient. Two patients needed flap revision due to bulkiness. The postoperative mouth opening was 18-38 mm (mean 28.2mm) after a mean of 21 months' follow-up, and the mean increase was 25.9 mm. A bipaddled radial forearm flap, using a single donor site, can cover two separate buccal defects after release of oral submucosal fibrosis and obviate the need for a second free flap.

Long-term follow-up of giant serpentine MCA aneurysm treated with EC-IC bypass and proximal occlusion.

Giant serpentine aneurysms are a rare but important subset of giant aneurysms, with unique management considerations. We present long-term follow-up clinical and imaging features of a giant serpentine middle cerebral artery lesion treated with extracranial-intracranial bypass and proximal occlusion more than a decade earlier. Calcification of the obliterated aneurysm sac and durability of this management strategy are demonstrated.

[Determination of tetramethylpyrazine in animal serum and cerebrospinal fluid by high performance liquid chromatography].

A reversed-phase high performance liquid chromatographic (RP-HPLC) method for the determination of the tetramethylpyrazine(TMP) in Chuanxiong extract, the animal(mouse) serum and cerebrospinal fluid has been developed. The TMP was separated on an ODS column Zorbax SB-C18(4.6 mm i.d. x 250 mm, 5 microns) at room temperature and detected by using UV detector at 270 nm. The mobile phase was methanol-water (50:50, V/V) containing 0.2 mmol/L of NH4H2PO4 flowing at a rate of 0.8 mL/min and 20 microL samples were injected. The detection limit of TMP was 1 mg/L and the calibration curve is linear between 5 and 500 mg/L with a correlation coefficient (r) of 0.999. The recovery of TMP ranged 98%-103%. The extract of Chuanxiong and pretreated serum and cerebrospinal fluid sample are stable for a week at room temperature.

[Studies on the active constituents of sichuan liang shan rhododendron L. I. Determination of two flavonoids in leaves, extracts and jinjuan liquors].

A reversed-phase HPLC method for the separation and determination of the two flavonoids: quercetin and kaempferol is described. The column was 25 cm x 4.6 mm i.d., packed with Zorbax SB-C18(5 microns). The mobile phase was a mixture of MeOH-H2O (60:40, V/V). The flow rate was 0.7 mL/min. UV detection was performed at 360 nm. External standard was used and the calibration curves showed good linearity over the range of 6.0-100 mg/L, r = 0.9995-0.9998, and detection limits were 3.3-6.2 mg/L. The recoveries were 96.0% and 97.3% for quercetin and kaempferol respectively. The relative standard deviations of the method were 2.1%-4.5%. The method is simple, fast, sensitive and accurate and can be applied to the analysis of quercetin and kaempferol. It provides a scientific basis for industrial production and quality control of Jinjuan liquor preparations for clinical uses.

Metabolism of 2,4,5,2',5'-pentachlorobiphenyl in the rat. Qualitative and quantitative aspects.

The metabolism of 2,4,5,2',5'-pentachloro [14C] biphenyl (5-CB) was studied in the male rat. Following iv administration of 5-CB (0.6 mg/kg), 84% of the total dose was excreted within 7 days and 89% of the radioactivity excreted was in the form of 5-CB metabolites. Mass spectral and proton nuclear magnetic resonance analysis or chemical methods in conjunction with mass spectral analysis were used to identify the metabolites. The major metabolite was identified as 3'-hydroxy 5-CB. One minor metabolite was identified as the 3',4'-dihydrodiol of 5-CB and a second minor metabolite was tentatively identified as 3',4'-dihydroxy-5-CB. The relative amounts of 5-CB and its metabolites excreted in the urine and feces were also determined.