[The application of human genetic technology in the medical field urgently needs standardization].

Human gene editing technology is a hot spot and focus in the development of biotechnology, but it has also caused controversies over technical risks, genetic biosecurity, ethical dignity of human society and the legality of application, causing people to worry about the application of this technology. Gene editing for reproductive purposes is generally prohibited internationally, and countries have established legal regulatory systems to regulate the application of gene editing technology according to their own conditions. China shall establish a security risk access system for gene editing technology, ensure national biosecurity, establish and improve the system of ethical norms for scientific research, improve the construction of legislative standardization, and provide legal guarantees for the research and application of gene editing technology.

[Analysis of risk factors of short-term prognosis in patients with severe Budd-Chiari syndrome].

Objective: To explore the risk factors of short-term prognosis of severe Budd-Chiari syndrome (BCS) patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value. Methods: This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group (n=38) and the survival group (n=133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model's differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results: Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time were independent risk factors (P<0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P-values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions: The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.

[Effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease: a multicenter study].

Objective: To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD). Methods: A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results: A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion: The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

[Clinical value of the MeltPro MTB assays in detection of drug-resistant tuberculosis in paraffin-embedded tissues].

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.

[The value of cell free DNA of Mycobacterium tuberculosis in the early diagnosis of tuberculous meningitis].

Objective: To detect the cell-free DNA of Mycobacterium tuberculosis (Cf-TB) in the cerebrospinal fluid (CSF) of patients with tuberculous meningitis (TBM), and to assess the diagnostic value of this method for TBM. Methods: We prospectively included patients with suspected meningitis from the Department of Tuberculosis, Beijing Chest Hospital, Department of Neurology, Beijing Chaoyang Hospital and Department of Neurology, 263 Hospital of the People's Liberation Army from September 2019 to March 2022. A total of 189 patients were included in this study. Among them, 116 were male and 73 were female, aged from 7 to 85 years, with an average of (38.5±19.1) years. The CSF specimens of the patients were collected for Cf-TB, MTB culture and Xpert MTB/RIF. SPSS 20.0 was used for statistical analysis and the difference was statistically significant with P<0.05. Results: Among the 189 patients, there were 127 patients in the TBM group and 62 patients in the non-TBM group. The sensitivity of Cf-TB was 50.4% (95%CI 41.4%-59.3%), the specificity was 100% (95%CI 92.7%-100.0%), the positive predictive value was 100% (95%CI 92.9%-100.0%), and the negative predictive value was 49.6% (95%CI 40.6%-58.6%). Using clinical diagnosis as the gold standard, the sensitivity of Cf-TB was 50.4% (64/127), which was significantly higher than that of MTB culture (8.7%, 11/127) and Xpert MTB/RIF (15.7%,20/127) (all P<0.001). Using etiology as the gold standard, the sensitivity of Cf-TB was 72.7% (24/33), which was significantly higher than that of MTB culture [33.3%, 11/33, (χ2=10.28, P=0.001)] and was similar to Xpert MTB/RIF (60.6%, 20/33) (χ2=1.091, P=0.296). Conclusion: The sensitivity of the Cf-TB test was significantly higher than that of CSF MTB culture and Xpert MTB/RIF. Cf-TB may provide evidence for earlier diagnosis and treatment of TBM.

[Emphasizing the standard application of toric intraocular lenses].

In the era of refractive cataract surgery, corneal astigmatism is a crucial factor that affects visual quality after cataract surgery. Toric intraocular lenses (IOLs) have a wide correction range, good surgical predictability, minimal damage to the ocular surface, and stable long-term effects, which can significantly improve postoperative visual quality and patient satisfaction. However, there are still several challenges in the clinical application of toric IOLs, including the awareness of astigmatism correction, the accuracy of preoperative biometry, the widespread adoption of the concept of total corneal astigmatism, the management of surgical planning and details, and the control of postoperative residual astigmatism. This article aims to address these issues to further standardize the clinical application of toric IOLs and help improve the overall level of refractive cataract surgery in China.

Beneficial effect of melatonin administration on the function of frozen-thawed rat testicular grafts.

BACKGROUND: Spermatogonia in testis is sensitive to the cytotoxicity of chemotherapy agents. Cryopreservation of testicular tissue may offer fertility restoration in young male cancer survivors. OBJECTIVE: To investigate the effect of melatonin on the survival of testicular grafts following cryopreservation and transplantation. MATERIALS AND METHODS: Wister rats were randomly allocated into three groups: control group; saline group (cryopreservation + autograft + saline); and melatonin group (cryopreservation + autograft + melatonin). Malondialdehyde (MDA) content, glutathione peroxidase (GPx) activity and superoxide dismutase (SOD) activity were assessed on day 7 after autograft transplantation. At day 30, graft recovery, spermatogonia per round tubule, and serum testosterone concentration in grafts were measured. RESULTS: Melatonin significantly diminished MDA content, enhanced GPx and SOD activities. Furthermore, the recovery rate, number of spermatogonia per round tubule, and serum testosterone concentration in melatonin group was markedly higher than the saline group. CONCLUSION: Melatonin administration at 20 mg/kg is effective in improving the function of frozen and thawed rat testicular graft. The protective role of melatonin can be attributed partly to the enhanced ROS scavenging and antioxidant enzyme activities. doi.org/10.54680/fr22310110612.

[Comparison on the clinical characteristics of patients with Takotsubo syndrome from China and from Europe/North America].

Objective: To summarize the clinical characteristics of patients with Takotsubo syndrome (TTS) from China and compare these features with patients from Europe/North America. Methods: We reviewed case reports published between 1990 and 2020 with the key words of "Takotsubo syndrome" "stress cardiomyopathy" "apical balloon syndrome" and "broken heart syndrome", in Wanfang, CNKI, Pubmed and Web of Science databases, and 1 294 articles were identified, including 128 articles reporting 163 cases in China and 1 166 articles reporting 1 256 cases in Europe/North America. The characteristics of demographics, triggers, symptoms, electrocardiogram, echocardiography, left ventriculogram,coronary angiography, treatment and prognosis were analyzed and compared between Chinese and European/North American cases. Results: A total of 1 294 articles (1 419 cases: 163 from China, 1 256 from Europe/North America) were included in the final analysis. The characteristics of Chinese cases included: (1) demographic:the age was (59.6±16.9) years, which was similar with that of European/North American ((59.7±17.4) years, P=0.90), and female accounting for 78.5% (128/163), which was lower than that of European/North American (85.4% (1 073/1 256), P=0.02). (2) Triggers:mental triggers accounted for 48.5% (79/163), physical triggers accounted for 43.6% (71/163), and no triggers accounted for 7.9% (13/163), respectively. Compared with Europe/North America, the ratio of patients with mental triggers was higher in China, while the ratio of patients with physical triggers and no triggers was lower (P<0.05). (3) Symptoms: chest pain (52.8% (86/163)), chest tightness (35.0% (57/163)), shortness of breath (33.1% (54/163)), dizziness (16.0% (26/163)), sweating (15.3% (25/163)), palpitations (12.3% (20/163)), syncope (9.2% (15/163)) abdominal pain/diarrhea (8.6% (14/163)), hypotension (7.4% (12/163)), and fatigue (1.2% (2/163)) were illustrated in sequence. Compared with patients in Europe/North America, the ratio of patients with chest tightness, dizziness, sweating, palpitations, abdominal pain/diarrhea was higher in Chinese patients, while the ratio of patients with hypotension was lower in Chinese patients (P<0.05). (4) Electrocardiogram: main manifestations were myocardial ischemia symptoms, such as ST-segment elevation (63.8% (104/163)), T wave inversion (46.0% (75/163)), ST-segment depression (8.6% (14/163)). Compared with European/North American, the ratio of patients with ST-segment elevation, T wave inversion, and atrioventricular block was higher in Chinese patients (P<0.05). (5) Echocardiography and imaging:apical dyskinesia (59.5% (97/163)) and apical/left ventricular bulbar dilation (36.2%(59/163)) dominated the echocardiography findings. Compared with European/North American, the ratio of patients with apical dyskinesia, apical/left ventricular bulbar dilation, and mitral regurgitation was higher in Chinese patients, while the ratio of patients with dyskinesia in other parts and left ventricular ejection fraction<50% was lower in Chinese patients (P<0.05). Left ventricular angiography showed 36.2% (59/163) of apical dyskinesia in Chinese patients, which was higher than that reported in European/North American patients, and 38.7% (63/163) of apical/left ventricular bulbar dilation was reported in Chinese patients, which was similar to that reported in European/North American patients. Coronary angiography showed percent of no stenosis or stenosis less than 50% was 87.1% (142/163), which was similar to that reported in European/North American patients (P>0.05). The typical type of TTS accounted for 96.3% (157/163), which was significantly higher than that reported in European/ American patients, while the ratio of basal type and midventricular type was lower (P<0.01). (6) Treatment and prognosis:the applied drugs in China were listed in order as following, ß-blockers (41.1% (67/163)), antiplatelet agents (37.4%(61/163)), ACEI/ARB (36.2%(59/163)), anticoagulants (27.0%(44/163)), diuretics (19.6% (32/163)), etc. Compared with Europe/North America, the ratio of antiplatelet agents, anticoagulants, statins, diuretics, and nitrates use was higher in China (P<0.05), while the use of oxygen therapy and IABP was similar (P>0.05). The hospital mortality in China was 5.5% (9/163), during 1-year follow-up the recurrence rate was 3.7% (6/163) and the mortality was 0. The prognosis was similar with that in Europe/North America. Conclusions: Compared with TTS cases in Europe/North America, TTS cases in China also occur usually in middle-aged and elderly women, most of whom have mental/physical triggers and typical imaging manifestations, followed by a low hospital mortality rate and recurrence rate.

[Spatial and temporal distribution and predictive value of chest CT scoring in patients with COVID-19].

Objective: To explore a modified CT scoring system, its feasibility for disease severity evaluation and its predictive value in coronavirus disease 2019 (COVID-19) patients. Methods: This study was a multi-center retrospective cohort study. Patients confirmed with COVID-19 were recruited in three medical centers located in Beijing, Wuhan and Nanchang from January 27, 2020 to March 8, 2020. Demographics, clinical data, and CT images were collected. CT were analyzed by two emergency physicians of more than ten years' work experience independently through a modified scoring system. Final score was determined by average score from the two reviewers if consensus was not reached. The lung was divided into 6 zones (upper, middle, and lower on both sides) by the level of trachea carina and the level of lower pulmonary veins. The target lesion types included ground-glass opacity (GGO), consolidation, overall lung involvement, and crazy-paving pattern. Bronchiectasis, cavity, pleural effusion, etc., were not included in CT reading and analysis because of low incidence. The reviewers evaluated the extent of the targeted patterns (GGO, consolidation) and overall affected lung parenchyma for each zone, using Likert scale, ranging from 0-4 (0=absent; 1=1%-25%; 2=26%-50%; 3=51%-75%; 4=76%-100%). Thus, GGO score, consolidation score, and overall lung involvement score were sum of 6 zones ranging from 0-24. For crazy-paving pattern, it was only coded as absent or present (0 or 1) for each zone and therefore ranging from 0-6. Results: A total of 197 patients from 3 medical centers and 522 CT scans entered final analysis. The median age of the patients was 64 years, and 54.8% were male. There were 76(38.8%) patients had hypertension and 30(15.3%) patients had diabetes mellitus. There were 75 of the patients classified as moderate cases, as well as 95 severe cases and 27 critical cases. As initial symptom, dry cough occurred in 170 patients, 134 patients had fever, and 125 patients had dyspnea. Reparatory rate, oxygen saturation, lymphocyte count and CURB 65 score on admission day varied among patients with different disease severity scale. There were 50 of the patients suffered from deterioration during hospital stay. The median time consumed for each CT by clinicians was 86.5 seconds. Cronbach's alpha for GGO, consolidation, crazy-paving pattern, and overall lung involvement between two clinicians were 0.809, 0.712, 0.678, and 0.906, respectively, showing good or excellent inter-rater correlation. There were 193 (98.0%) patients had GGO, 147 (74.6%) had consolidation, and 126(64.0%) had crazy-paving pattern throughout clinical course. Bilateral lung involvement was observed in 183(92.9%) patients. Median time of interval for CT scan in our study was 7 days so that the whole clinical course was divided into stages by week for further analysis. From the second week on, the CT scores of various types of lesions in severe or critically patients were higher than those of moderate cases. After the fifth week, the course of disease entered the recovery period. The CT score of the upper lung zones was lower than that of other zones in moderate and severe cases. Similar distribution was not observed in critical patients. For moderate cases, the ground glass opacity score at the second week had predictive value for the escalation of the severity classification during hospitalization. The area under the receiver operating characteristic curve was 0.849, the best cut-off value was 5 points, with sensitivity of 84.2% and specificity of 75.0%. Conclusions: It is feasible for clinicians to use the modified semi-quantitative CT scoring system to evaluate patients with COVID-19. Severe/critical patients had higher scores for ground glass opacity, consolidation, crazy-paving pattern, and overall lung involvement than moderate cases. The ground glass opacity score in the second week had an optimal predictive value for escalation of disease severity during hospitalization in moderate patients on admission. The frequency of CT scan should be reduced after entering the recovery stage.

[Analysis of early recurrence within 6 months in patients of esophageal squamous cell carcinoma after neoadjuvant therapy followed by surgery].

Objectives: To examine the prognosis factors of recurrence of esophageal carcinoma within 6 months after neoadjuvant therapy followd by surgery. Methods: The clinical data of 187 patients with esophageal squamous cell carcinoma who underwent neoadjuvant therapy followed by curative esophagectomy between January 2018 and April 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital were analyzed retrospectively. There were 160 males and 27 females, aging (63.0±7.1) years (range:43 to 76 years). The t test, χ2 test and rank-sum test were used for univariate analysis of the prognosis factors for recurrence within 6 months postoperative, while the Logistic regression was used for multivariate analysis. Results: There were 30 patients (16.0%) developed recurrence within 6 months after operation, including local recurrence in 1 case, regional recurrence in 11 cases, hematogenous recurrence in 13 cases, and combined recurrence in 5 cases. Univariate analysis suggested that there was a significant difference in T staging of tumor before neoadjuvant therapy (cT), tumor regression grade, circumferential resection margin, pathological T stage (ypT) and pathological N stage (ypN) between the recurrence patients and non-recurrence patients (all P<0.05). Logistic regression analysis suggested that the cT3-4 (OR=2.701, 95%CI: 1.161 to 6.329, P=0.021) and ypN(+)(OR=1.654, 95%CI: 1.045 to 2.591, P=0.032) were the independent prognosis factors for recurrence within 6 months. Conclusion: The combination of neoadjuvant therapy and surgery is not effective in reducing early postoperative recurrence in patients who have invaded the epineurium before treatment, and still have positive lymph nodes after neoadjuvant therapy.

[Pathological characteristics and molecular diagnosis of non-tuberculosis Mycobacterium lung disease].

Objective: To investigate the clinicopathological features of non-tuberculosis mycobacterial lung disease and the role of molecular pathology in diagnosis. Methods: Forty-five formalin-fixed, paraffin embedded (FFPE) specimens were collected from the Department of Pathology, Beijing Chest Hospital from February 2016 to August 2019. The clinical, imaging and histopathologic features, bacteriologic data and morphologic characteristics of acid fast bacilli (AFB) were analyzed retrospectively. Specific gene sequence IS6110 of Mycobacterium tuberculosis (MTB) was detected by fluorescence PCR. Identification of Mycobacteria was by melting curve method. Fifty cases of pulmonary tuberculosis were selected in the same period as control. Results: The NTM lung cases included 18 cases (40.0%, 18/45) of M. intracellulare, eight cases (17.8%, 8/45) of M. xenopi, six cases (13.3%, 6/45) of M. avium, six cases (13.3%, 6/45) of M. kansasii, six cases (13.3%, 6/45) of M. chelonae and one case (2.2%, 1/45) of M. simiae. Histopathologically, there were necrotizing granulomas in 34 cases (75.6%, 34/45), non-necrotizing granuloma in one case (2.2%, 1/45) and non-granulomatous lesions in 10 cases (22.2%, 10/45). The necrosis was pink necrosis, basophilic necrosis rich in nuclear fragments and suppurative necrosis. Pulmonary TB showed more pink necrosis and basophilic necrosis, the difference was statistically significant (χ(2)=10.270, P=0.001; χ(2)=7.449, P=0.006). Seventeen cases (37.8%, 17/45) of NTM lung disease showed giant multinucleated giant cells, which were significantly different from those in pulmonary tuberculosis group (χ(2)=13.446, P<0.01). The number and morphology of AFB were also different. More AFB were found in M. intracellular cases and significant AFB were easily seen in M. kansasii infection. Conclusions: M. tuberculosis and NTM cannot be reliably differentiated by histologic features or by AFB morphology. Molecular assays are important to distinguish tuberculosis from NTM lung disease.

[Detection of tuberculosis genes associated with drug-resistance in paraffin-embedded tissue specimens using next generation sequencing technology].

Objective: To evaluate the use of multiplex PCR amplicon sequencing (mPCR-NGS) technology in detecting gene mutations related to drug resistance of Mycobacterium tuberculosis (MTB) in formalin-fixed paraffin-embedded tissue specimens, and to explore its clinical value in the diagnosis of drug-resistant tuberculosis. Methods: Fifty clinical MTB strains isolated in the Changping District Tuberculosis Control Institute of Beijing from April 2013 to October 2015 with drug susceptibility test (DST) results of rifampicin, isoniazid, ethambutol, streptomycin, ofloxacin, capreomycin, kanamycin and amikacin available were recovered, including 42 drug-resistant strains and 8 drug-sensitive strains. The mPCR-NGS test was established to detect genes related to the 8 anti-tuberculosis drugs according to the previously published studies and databases. Fifty-five paraffin-embedded tissue specimens from drug-resistant tuberculosis patients were collected in the Department of Pathology, Beijing Chest Hospital, Capital Medical University during November 2017 to September 2018. All the specimens showed no less than one mutation in the gene regions related to drug resistance of any of the 4 drugs (rifampicin, isoniazid, ethambutol or fluoroquinolones) by probe melting curve assay. The effectiveness of mPCR-NGS test was evaluated on clinical MTB isolates using phenotypic DST as the reference. Clinical evaluation of mPCR-NGS test on formalin-fixed paraffin-embedded specimens from TB patients was performed using probe melting curve assay as the reference. The sensitivity, specificity and coincidence of mPCR-NGS were analyzed. Results: Using phenotypic DST as the reference, the sensitivities of the mPCR-NGS for detecting drug-resistance of rifampicin, isoniazid, streptomycin, and ethambutol were 95% (38/40), 93% (27/29), 93% (27/29), and 72% (13/18), respectively; and the specificities were 100% (10/10), 95% (20/21), 100% (21/21), and 94% (30/32), respectively. The sensitivities for capreomycin, kanamycin and amikacin were all 100% (2/2, 3/3, 3/3), and the specificities were 98% (47/48), 100% (33/33) and 100% (47/47), respectively. The sensitivity and specificity of ofloxacin were 70% (7/10) and 100% (40/40), respectively. The total coincidence rate for the 8vdrugs was 94%, and the Kappa value was 0.87. The 55 paraffin-embedded tissue specimens included in this study were all tested by probe melting curve assays. Among them 28 were resistant to rifampicin, 37 resistant to isoniazid, 13 resistant to ethambutol, and 17 resistant to fluoroquinolones. Using the probe melting curve assay as the reference, the sensitivities of the mPCR-NGS for detecting resistant to rifampicin, isoniazid, ethambutol, and fluoroquinolones were 100% (28/28), 95% (35/37), 100%, and 100%, respectively; and the specificities were all 100% (42/42, 38/38). The total coincidence rate of the two methods was 99%, and the Kappa value was 0.98. Conclusions: mPCR-NGS showed good sensitivities and specificities in detecting drug-resistant gene mutations both in clinical MTB isolates and paraffin-embedded tissue specimens. mPCR-NGS has the potential to be an accurate and rapid molecular pathological technology for diagnosis of drug-resistant tuberculosis.

[Estimating the burden of influenza-associated hospitalization for cases of severe acute respiratory infection, Beijing, 2015].

Objective: To estimate the influenza infection rate among severe acute respiratory infection(SARI) cases and the hospitalization rates of SARI attributable to influenza, based on two sentinel hospital surveillance databases in Beijing, 2015. Methods: Surveillance was conducted at two sentinel hospitals in Beijing in 2015. A total of 1 842 patients who admitted to the sentinel hospitals and met the definition of SARI were enrolled in the study. The respiratory tract specimens of SARI cases were collected, and sent to laboratories within 48 hours for influenza RNA detection. The catchment area of sentinel hospitals was defined by reviewing the home address of inpatients; A total of 1 491 patients were sampled and tested for influenza. The population size of catchment areas was obtained from demographic year book. We investigated the number of pneumonia patients admitted to the sentinel hospitals and other hospitals in catchment areas in 2015, and calculated the proportions of pneumonia patients that were admitted to sentinel hospitals in catchment areas. The catchment population size was calculated using the number of total population of catchment areas multiply by the proportions of pneumonia patients that were admitted at sentinel hospitals. Results: Among 1 491 patients, 13.7% (205 cases) was test positive for influenza viruses, 2 (0.9%) cases positive for influenza A (H1N1), 91 (44.6%) cases influenza A (H3N2), 1 (0.5%) case influenza B/Victoria, 111 (54.0%) cases influenza B/Yamagata. Influenza was associated with an estimated 30 (95%CI:9-51) SARI hospitalizations per 100 000 during 2015. The hospitalization rate was 243 (95%CI: 232-255), 86 (95%CI: 59-112),1(95%CI: 0-5), 8 (95%CI: 0-23) and 92 (95%CI: 16-168) SARI hospitalizations per 100 000 population for<5 years children, 5-14 years children, 15-24 years adult, 25-59 years adult and ≥60 years population, respectively. The hospitalization rate of SARI attributed to influenza A and B was 14 (95%CI:4-17) and 16 (95%CI:0-23) per 100 000 population, respectively. Conclusion: The influenza positive rate among SARI cases was relatively high. The hospitalization burden of SARI attributed to influenza was the greatest in children under 5 year-old.

Clinical Outcomes of Patients with Severe Hepatic Hereditary Hemorrhagic Telangiectasia After Banding of the Hepatic Artery and Banding/Ligation of Branches of the Hepatic Artery.

OBJECTIVE/BACKGROUND: To evaluate the effectiveness of double banding/ligation of hepatic arteries in treating patients with hepatic hereditary hemorrhagic telangiectasia (HHHT). METHODS: From January 2004 to December 2013, 35 patients were diagnosed with HHHT, among whom 11 woman and two men with a mean ± SD age of 44 ± 9 years were treated by double hepatic artery banding/ligation for cardiac insufficiency and/or portal hypertension. The outcomes were evaluated prospectively by measuring clinical manifestations, imaging features, liver and cardiac function, pulmonary arterial systolic pressure, and post-operative complications. Quality of life was evaluated with the Short Form Health Survey questionnaire. RESULTS: For each patient, the common hepatic artery and one branch of the left and/or right hepatic artery were banded, and other significantly dilated hepatic artery branches were ligated. No patient died after surgery. Clinical symptoms were improved in all patients, although ischemic cholangitis was observed in two patients and treated conservatively. Cardiac function, classified per the New York Heart Association (NYHA) cardiac functional grading, improved (NYHA III-IV vs. NYHA I-II); pulmonary arterial systolic pressure significantly decreased in all patients (48 ± 8 mmHg vs. 24 ± 4 mmHg; P < .001) and remained in the normal range (26 ± 3 mmHg) at the end of follow up. The levels of γ-glutamyl transpeptidase and alkaline phosphatase decreased in 11 patients (144 ± 94 U/L vs. 71 ± 34 U/L; P = .003) and 10 patients (207 ± 71 U/L vs. 105 ± 32 U/L; P = .001), respectively. Patients were followed up for 50 ± 28 months (range 6-113 months); one death resulted from causes unrelated to surgery and all dimensions of quality of life improved in all surviving patients. CONCLUSIONS: This study helps to establish double hepatic artery banding/ligation as an effective therapy for selected patients with HHHT.

Construction of a genetic linkage map and identification of QTL associated with growth traits in Malus sieversii.

110 F(1) individuals of apple were obtained by crossing between a good quality cultivar'Red Fuji'ofMalus domestica and an accession'Hongrou Apple'ofMalus sieversi. Using Joinmap3.0, a molecular genetic linkage map of Malus sieversii was constructed by 175 SSR and 105 SRAP markers which were integrated into 17 linkage groups and spanned 1299.67cM in genome with an average distance of 4.6cM between the markers. By using interval mapping method,17 QTLs for eight growth traits of Malus sieversii were detected, including 2 QTLs for tree height on cl and c16, 2 QTLs for stem height on c7, 2 QTLs for stem thickness on c3, 2 QTLs for new shoot length on c15 and c16, 2 QTLs for new shoot diameter on c2, 3 QTLs for internode number on c1, c2 and c2, 2 QTLs for internode length on c 1 and c2, 2 QTLs for lenticel density on c17, respectively. The phenotypic variations explained by each QTL ranged from 10.15% to 41.66%, and their LOD values varied from 2.54 to 4.53, of which five QTLs were major effect genes (LOD≥3.5).

Population pharmacokinetics of valnemulin in swine.

This study was carried out in 121 pigs to develop a population pharmacokinetic (PPK) model by oral (p.o.) administration of valnemulin at a single dose of 10 mg/kg. Serum biochemistry parameters of each pig were determined prior to drug administration. Three to five blood samples were collected at random time points, but uniformly distributed in the absorption, distribution, and elimination phases of drug disposition. Plasma concentrations of valnemulin were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration-time data were fitted to PPK models using nonlinear mixed effect modeling (NONMEM) with G77 FORTRAN compiler. NONMEM runs were executed using Wings for NONMEM. Fixed effects of weight, age, sex as well as biochemistry parameters, which may influence the PK of valnemulin, were investigated. The drug concentration-time data were adequately described by a one-compartmental model with first-order absorption. A random effect model of valnemulin revealed a pattern of log-normal distribution, and it satisfactorily characterized the observed interindividual variability. The distribution of random residual errors, however, suggested an additive model for the initial phase (<12 h) followed by a combined model that consists of both proportional and additive features (≥ 12 h), so that the intra-individual variability could be sufficiently characterized. Covariate analysis indicated that body weight had a conspicuous effect on valnemulin clearance (CL/F). The featured population PK values of Ka , V/F and CL/F were 0.292/h, 63.0 L and 41.3 L/h, respectively.

Estimation of the genetic parameters of sheep growth traits based on machine vision acquisition.

In the realm of animal phenotyping, manual measurements are frequently utilised. While machine-generated data show potential for enhancing high-throughput breeding, additional research and validation are imperative before incorporating them into genetic evaluation processes. This research presents a method for managing meat sheep and collecting data, utilising the Sheep Data Recorder system for data input and the Sheep Body Size Collector system for image capture. The study aimed to investigate the genetic parameter changes of growth traits in Ujumqin sheep by comparing machine-generated measurements with manual measurements. The dataset consisted of 552 data points from the offspring of 75 breeding rams and 399 breeding ewes. Six distinct random regression models were assessed to pinpoint the most suitable model for estimating genetic parameters linked to growth traits. These models were distinguished based on the inclusion or exclusion of maternal genetic effects, maternal permanent environmental effects, and covariance between maternal and direct genetic effects. Fixed factors such as individual age, individual sex, and ewe age were taken into account in the analysis. The genetic parameters for the yearling growth traits of Ujumqin sheep were calculated using ASReml software. The Akaike information criterion, the Bayesian information criterion, and fivefold cross-validation were employed to identify the optimal model. Research findings indicate that the most accurate models for manually measured data revealed heritability estimates of 0.12 ± 0.15 for BW, 0.05 ± 0.07 for body slanting length, 0.03 ± 0.07 for withers height, 0.15 ± 0.12 for hip height, 0.11 ± 0.11 for chest depth, 0.13 ± 0.13 for shoulder width, and 0.53 ± 0.15 for chest circumference. The optimal models for machine-predicted data showed heritability estimates of 0.1 ± 0.09 for body slanting length, 0.14 ± 0.12 for withers height, 0.55 ± 0.15 for hip height, 0.34 ± 0.15 for chest depth, 0.26 ± 0.15 for shoulder width, and 0.47 ± 0.16 for chest circumference. In manually measured data, genetic correlations ranged from 0.35 to 0.99, while phenotypic correlations ranged from 0.07 to 0.90. In machine data, genetic correlations ranged from -0.05 to 0.99, while phenotypic correlations ranged from 0.03 to 0.84. The results suggest that machine-based estimations may lead to an overestimation of heritability, but this discrepancy does not impact the selection of breeding models.

Record performance of electrical injection sub-wavelength metallic-cavity semiconductor lasers at room temperature.

We demonstrate a continuous wave (CW) sub-wavelength metallic-cavity semiconductor laser with electrical injection at room temperature (RT). Our metal-cavity laser with a cavity volume of 0.67λ3 (λ = 1591 nm) shows a linewidth of 0.5 nm at RT, which corresponds to a Q-value of 3182 compared to 235 of the cavity Q, the highest Q under lasing condition for RT CW operation of any sub-wavelength metallic-cavity laser. Such record performance provides convincing evidences of the feasibility of RT CW sub-wavelength metallic-cavity lasers, thus opening a wide range of practical possibilities of novel nanophotonic devices based on metal-semiconductor structures.

Isolation of novel microsatellite markers from Paralichthys lethostigma (Paralichthyidae) and their cross-species application in Pleuronectiformes.

We investigated the genetic diversity of the southern flounder Paralichthys lethostigma. Microsatellite-enriched libraries were constructed and novel microsatellite markers were developed and applied for genetic detection of wild populations. Cross-species amplification was also conducted in five pleuronectiforme species. Of 45 randomly selected and sequenced clones, 43 contained a CA or GA repeat motif. Fourteen pairs of primers were designed to investigate the polymorphism and genetic structure of a wild population collected from North Carolina State coastal waters. Two loci were monomorphic and 12 loci were polymorphic. The number of alleles per polymorphic locus ranged from 2 to 16, with an average of 7.3, and the expected heterozygosity per locus ranged from 0.10 to 0.92, with an average of 0.58. Cross-species amplification showed that most of the markers could successfully amplify Paralichthys olivaceus DNAs, few markers amplified in Verasper variegatus and Verasper moseri, and none of them could amplify Scophthatmus maximus and Cynoglossus semilaevis DNAs. The isolated polymorphic markers would be useful for the genetic breeding and assessment of genetic variation within the genus Paralichthys.