[Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study].

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34 ~ 21.15) µmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31 ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) µmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) µmol/L, respectively. Conclusion: The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.

Induction of apoptosis by capsaicin in hepatocellular cancer cell line SMMC-7721 is mediated through ROS generation and activation of JNK and p38 MAPK pathways.

Capsaicin, one of the major pungent ingredients found in red peppers, has been shown to have anti-carcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human hepatocellular cancer cell line SMMC-7721, as well as the possible mechanisms involved. Treatment of SMMC-7721 cells with capsaicin resulted in a dose-dependent inhibition of cell-viability and induction of apoptosis which was associated with the generation of ROS and persistent disruption of mitochondrial membrane potential. These effects were significantly blocked when cells were pretreated with a general antioxidant N-acetyl cysteine (NAC). We also found that capsaicin induced JNK and p38 MAPK phosphorylation. JNK and p38 MAPK inhibitor effectively blocked capsaicin-induced SMMC-7721 cell apoptosis. In addition, NAC completely blocked phosphorylation of JNK and p38 MAPK induced by capsaicin. Our results indicate that capsaicin induced in SMMC-7721 cell apoptosis through generation of intracellular ROS and activation of JNK and p38 MAPK pathways.

First Report of Lily Blight and Wilt Caused by Fusarium tricinctum in China.

Lily (Lilium spp.) is one of the most well-known horticultural crops, and plays an important economic role in China. In September 2011, wilted plants were observed on Lilium oriental hybrid cultivar 'Sorbonne' growing in Longde County, Ningxia Hui Autonomous Region, China. Disease symptoms included wilting, stem and root rot, brown spots of bulbs and then bulbs rotting and spalling from the basal disc, plus a progressive yellowing and defoliation of the leaves from the base. Diseased plants were sampled from fields. Small pieces of symptomatic bulbs, stems, and roots from 10 different plants were surface disinfected with 75% ethanol for 30 s, 3% sodium hypochlorite for 5 min, and then washed three times in sterilize distilled water. The tissues were placed onto Martin Agar (2) at 25°C for 7 days. Nine isolates with morphology similar to Fusarium were obtained from the diseased tissues. Isolates were transferred to potato dextrose agar (PDA) and carnation leaf agar (CLA) and incubated at 25°C. Seven were identified as Fusarium oxysporum and one was F. solani, which have been reported as pathogens of lily in China (1). The other isolate, when grown on PDA, rapidly produced dense, white aerial mycelium that became pink with age and formed red pigments in the medium. On CLA, macroconidia with three to five septate were abundant, relatively slender, and curved to lunate. Microconidia were abundant, oval or pyriform, and one to two celled. Chlamydospores were in chains with smooth exine. The rDNA internal transcribed spacer (ITS) region and a portion of the translation elongation factor 1-alpha (EF-1α) gene of the fungus were amplified, with universal primers ITS1/ITS4 and EF1/EF2 primers respectively (3) and sequenced. In addition, the ß-tubulin gene (ß-tub) of the fungus was amplified with modified primers Btu-F-F01 (5'-CAGACMGGTCAGTGCGTAA-3') and Btu-F-R01 (5'-TCTTGGGGTCGAACATCTG-3') (4). BLASTn analysis showed that the ITS sequences of the isolate (GenBank Accession No. JX989827) had 98.9% similarity with those of F. tricinctum (EF611092, JF776665, and HM776425) and the EF-1α sequences of the isolate (JX989828) had 98.1% similarity with those of F. tricinctum (EU744837 and JX397850). The ß-tub sequences of the isolate (JX989829) had 99.0% similarity with those of F. tricinctum (EU490236 and AB587077). The isolate was tested for pathogenicity. Two-month-old 'Sorbonne' seedlings were inoculated by placing 5 ml of conidial suspension (about 106 conidia per ml) over the roots of plants in each pot. Control plants were treated with sterile water in the same way. Plants were placed in a greenhouse at 22 to 25°C with a 15-h photoperiod. There were eight plants per pot and three replicates for each treatment. After 3 weeks, 87.5% of the inoculated plants exhibited browning of the root tips, root rot, and yellowing of the leaves, while control plants were symptomless. The pathogen was reisolated from the infected roots and identified as F. tricinctum, thus fulfilling Koch's postulates. To our knowledge, this is the first report of Fusarium wilt of lily caused by F. tricinctum. This information will provide guidance for the control of lily wilt disease and add information useful for the production of lilies. References: (1) C. Li and J. J. Li. Acta Phytopathol. Sin. (in Chinese) 26:192, 1995. (2) J. P. Martin. Soil Sci. 38:215, 1950. (3) K. O'Donnell et al. Proc. Nat. Acad. Sci. U. S. A. 95:2044, 1998. (4) M. Watanabe et al. BMC Evol. Biol. 11:322. 2011.

Characterization of Th1- and Th2-type immune response in human multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) has become a lethal global threat. Insights into the immune regulation of MDR-TB are urgently needed for the development of new treatments; however, the T cell response to an MDR-TB infection in human remains unclear. In the present study, the proportion of Th1 and Th2 cell subsets and the level of related T cell subset cytokines in peripheral blood were investigated. We detected that an MDR-TB infection resulted in suppressed Th1 and Th2 cell activation, which was more remarkable in patients with MDR-TB than that in drug-sensitive tuberculosis (DS-TB) sufferers when compared to healthy controls (HCs). In addition, MDR-TB infection down-regulated the expression of IFN-γ, IL-2, and IL-10, and up-regulated IL-4, IL-6, and TNF-α expression. Our data suggest that the disturbance between protective and pathogenic effects induced by the immunosuppression of Th1- and Th2-type responses is a substantial characteristic of MDR-TB infections.

[Incidence and outcome of anti-tuberculosis drug-induced hepatotoxicity in tuberculosis inpatients].

OBJECTIVE: Based on the medical records and follow-up records of hospitalized patients who received anti-tuberculosis therapy in the Third People's Hospital of Zhenjiang in Jiangsu province from 2006 to 2012, we investigated the incidence and outcome of anti-tuberculosis drug induced hepatotoxicity(ATDH)and provided evidence for the prevention of ATDH. METHODS: According to tuberculosis patients' medical information and liver function test records, ATDH patients were diagnosed according to the criteria of International Consensus Meeting and American Thoracic Society respectively, then the related factors and outcomes were analyzed. RESULTS: A total of 1 967 hospitalized tuberculosis patients were reviewed retrospectively, in which 1 403(71.3%)were men, 1 790(91.0%)were pulmonary tuberculosis patients, 1 528(77.8%)were patients receiving initiative treatment, 979(49.8%)were sputum smear-positive patients, and 1 297(65.9%)had other complicated diseases. According to the criterion of International Consensus Meeting, the incidence of ATDH was 16.5%, the median time of onset was 25 days. According to the criterion of American Thoracic Society, the incidence of ATDH was 8.3%, the median time of onset was 23 days. The incidence of ATDH was significantly higher in males and HRZE therapy group(P<0.05). Under the two liver criteria, 69.5% and 70.1% of the patients changed primary therapy respectively after ATDH occurred. 89.8% and 88.4% patients' liver function returned to normal range after changing or stopping therapy. CONCLUSION: According to two liver injury criteria, the incidences of ATDH were 16.5% and 8.3% in hospitalized tuberculosis patients respectively, and ATDH mainly occurred in the first month of anti-tuberculosis treatment. The monitoring of liver function should be strengthened in males and HRZE therapy group to reduce the incidence of ATDH.

A transcription map of the minimally deleted region from 13q14 in B-cell chronic lymphocytic leukemia as defined by large scale sequencing of the 650 kb critical region.

Extensive analysis of tumors has demonstrated homozygous and heterozygous deletions in chromosome region 13q14.3 in B-cell chronic lymphocytic leukemia (B-CLL), suggesting the site of a tumor suppressor gene. Since previous searches for this gene have not yielded any viable candidates, we now present the sequence of the BACs which span the minimally deleted approximately 650 kb region between markers D13S319 and D13S25. This sequence has allowed us to create the definitive transcription map for the region which reveals 93 ESTs and 12 Unigene clusters in this region. Using gene prediction programs, a further 19 potential genes are also identified. The genes show an asymmetrical distribution throughout the region with most of them clustering at the extreme ends. This sequencing effort provides for the definitive structure of the B-CLL deletion region and the identification of the vast majority of the potential candidate genes. Of all the genes identified, only three have homologies to known genes: two L1 repeat genes and rabbit epididymal protein 52. This 13q14.3 sequence provides the final substrate from which to characterize the B-CLL tumor suppressor gene.

Expression of receptor protein tyrosine kinase tif is regulated during leukemia cell differentiation.

tif is a recently cloned and characterized cDNA predicting a transmembrane protein with a putative tyrosine kinase structure in its cytoplasmic domain. By analysis of the purified tif cytoplasmic domain expressed in Escherichia coli, we have demonstrated that tif is an active protein tyrosine kinase capable of autophosphorylation on tyrosine residues and this phosphorylation is inhibited by a tyrosine-specific inhibitor genistein. Northern blot analyses of various leukemia cell lines have revealed that tif mRNA expression is primarily confined to those bearing erythroid and megakaryocytic phenotypes. Megakaryocytic differentiation of K562 and HEL cells induced by phorbol 12-myristate 13-acetate is accompanied by down-regulation of tif mRNA expression. In addition, treatment of K562 and HEL with hexamethylene bis-acetamide, but not with hemin, decreases the steady-state level of tif mRNA. These combined results suggest that the receptor tyrosine kinase tif is involved in hematopoietic development.

Characterization of the human NIPSNAP1 gene from 22q12: a member of a novel gene family.

Rapid progress in sequencing of human and other genomes allows high-resolution analysis of their gene content on the basis of comparison between species. We have used a combined computer and biochemical approach to characterize 135 kb of human genomic sequence from 22q12 and discovered a new 10 exon gene, termed NIPSNAP1, located between the neurofibromatosis type 2 and the pK1.3 genes. The NIPSNAP1 gene spans 26 kb of genomic sequence and shows to large introns in the 5'-region. All exon-intron junctions contain the gt/ag consensus splice site. The putative promoter of the NIPSNAP1 gene is TATA-less and resides in a GC-rich island characteristic of housekeeping genes. The NIPSNAP1 mRNA is 2.1 kb, is expressed ubiquitously at variable levels, with the highest expression in liver, is terminated by an uncommon ATTAAA polyadenylation site, and is capable of encoding a 284-amino-acid protein. This NIPSNAP1 protein has a strong sequence similarity limited to the central portion of a hypothetical protein (acc. P34492) from chromosome III of C. elegans, in which the other portions resemble a 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein. Thus, the NIPSNAP1 gene is a member of an evolutionarily well conserved, novel gene family with two members in human and mouse that have now been characterized, and one member in C. elegans. The second human gene, NIPSNAP2, is localized in the vicinity of marker D7S499 on chromosome 7. Although the function of the NIPSNAP protein family is unknown, clues about its role may reside in the co-expression of the C. elegans orthologue, within an operon encoding protein motifs known to be involved in vesicular transport.

The Maquet procedure: effect of tibial shingle length on patellofemoral pressures.

The Maquet procedure--elevation of the anterior tibial tubercle--has been recommended for treatment of symptomatic osteoarthrosis of the patellofemoral joint. Although the operation was first described 30 years ago, it remains controversial, both on a clinical and on a biomechanical basis. In addition, deterioration of the long-term results has been suggested. One of the variables that has been ignored in both clinical and biomechanical studies has been tibial shingle length. In order to judge its effect, we examined contact pressures and areas in 15 cadaver knees with 7 and 20 cm tibial shingle lengths. We found significant patellofemoral pressure diminution only with 2 cm elevations. The short anterior tibial shingle with 2 cm of elevation tipped the patella on its superior pole, with a significant change in angle between the patella and the shingle. We suggest that this creates a potentially less than desirable biomechanical circumstance and believe it may explain the discrepancies among previously published reports.

Absolute Rate Constants for Radical Additions to Alkenes in Solution. The Synergistic Effect of Perfluorination on the Reactivities of n-Alkyl Radicals1.

Laser flash photolysis has been used to determine the absolute rate constants for addition of several partially fluorinated n-alkyl radicals to three styrenes at 25 °C in Freon 113. Fluorination at the γ-position (RCF2CH2CH2•) gives radicals with essentially the same reactivity as non-fluorinated n-alkyls. The RCH2CF2CH2• and RCH2CH2CHF• radicals are both about three times as reactive as RCF2CH2CH2•, but the RCH2CH2CF2• radical is ca. five to six times rather than ca. three times as reactive as RCH2CH2CHF•. Similarly, the perfluorinated radical CF3CF2CF2• is much more reactive than would be expected on the basis of the reactivities of the RCH2CF2CH2• and RCH2CH2CF2• radicals. Thus, perfluorinated n-alkyl radicals are very considerably more reactive than would be predicted from the individual effects of α-, ß-, and γ-fluorination.

Progesterone is neuroprotective after acute experimental spinal cord trauma in rats.

STUDY DESIGN: A standardized rat contusion model was used to test the hypothesis that progesterone significantly improves neurologic recovery after a spinal cord injury that results in incomplete paraplegia. OBJECTIVES: To compare the effect of progesterone versus a variety of control agents to determine its effectiveness in promoting neurologic recovery after an incomplete rat spinal cord injury. SUMMARY OF BACKGROUND DATA: Progesterone is a neurosteroid, possessing a variety of functions in the central nervous system. Exogenous progesterone has been shown to improve neurologic function after focal cerebral ischemia and facilitates cognitive recovery after cortical contusion in rats. METHODS: A standardized rat contusion model of spinal cord injury using the New York University impactor that resulted in rats with incomplete paraplegia was used. Forty mature male Sprague-Dawley rats were randomly assigned to four groups: laminectomy with sham contusion, laminectomy with contusion without pharmacologic treatment, laminectomy with contusion treated with dimethylsulfoxide and dissolved progesterone, and laminectomy with contusion treated with dimethylsulfoxide. Functional status was assessed weekly using the Basso-Beattie-Bresnehan (BBB) locomotor rating scale for 6 weeks, after which the animals were killed for histologic studies. RESULTS: Rats treated with progesterone had better outcomes (P = 0.0017; P = 0.0172) with a BBB score of 15.5, compared with 10.0 in the dimethylsulfoxide control group and 12.0 in the spinal cord contusion without pharmacologic intervention group. This was corroborated in histologic analysis by relative sparing of white matter tissue at the epicenter of the injury in the progesterone-treated group (P < 0.05). CONCLUSIONS: Rats treated with progesterone had a better clinical and histologic outcome compared with the various control groups. These results indicate potential therapeutic properties of progesterone in the management of acute spinal cord injury.

[Effect of vitamin C (V.C) on thermal sensitivity of Lewis tumor].

In this paper, the effect of V.C on thermal sensitivity of the tumor and normal tissues was studied. Average peak reaction and RD50 (50% reaction dosage) were used to evaluate the effect of V.C on thermal sensitivity of the normal tissue. Tumor cure rate and TCD50 (50% tumor cure dosage) were used to evaluate the effect of V.C on that of the tumor tissue. In all mice injected by V.C locally, the average peak reaction markedly increased, RD50 decreased by 1-2 fold; the tumor cure rate was obviously elevated, TCD50 was significantly reduced except those treated by 20' hyperthermia. TGF (therapeutic gain factor) was 1.76. These results indicate that V.C can increase the thermal sensitivity of tumor and normal tissues but the effect on tumor tissue is selective.

[Scanning electron microscopic observation of microvascular cast changes of bone following rigid limb immobilization].

This paper reported the results of scanning electron microscopic observation of microvascular cast changes of tibia following long cast immobilization of lower extremity. Beginning from 10 days after immobilization, the diameter of microvessels, particularly capillaries and sinusoids system in bone marrow, displayed severalfold enlargement compared with the control side. The changes became more obvious at 20 days. The number of sinusoids increased whereas the degree of dilatation declined at 40 days. The vessels within the epiphyseal region also showed more intense dilatation, growth of sinusoid-like structure and proliferation of sinusoidal and capillary system in marrow at 60 to 80 days. Similar changes in the cortical bone emerged as well at 80 days. The above-mentioned changes decreased at 100 days. These results pointed out that the pump effect of muscle on the blood flow in bone almost disappeared completely and disturbance of intraosseous venous drainage occurred. Under the condition of increased but unbalanced bone metabolism and turnover, the intraosseous microvascular system exhibited the described changes. Thus the total bone blood volume and the total bone blood flow increased.

Analysis of the economic burden of diagnosis and treatment of tuberculosis patients in rural China.

SETTING: A county in Jiangsu Province, China. OBJECTIVES: To estimate the costs of the diagnosis and treatment of tuberculosis (TB) from the patient's perspective and to identify determinants of the patient's financial burden. DESIGN: In a cross-sectional survey, we interviewed 316 patients diagnosed from January 2010 to May 2011 who had already completed their anti-tuberculosis treatment. The financial burden on TB patients included out-of-pocket costs and productivity losses. RESULTS: The average per capita total out-of-pocket cost was 3024.0 Chinese yuan (CNY), with a median cost of 1086 CNY (interquartile range [IQR] 480-2456). Mean out-of-pocket medical and non-medical costs were respectively 2565.7 CNY and 458.3 CNY. Productivity lost by patients and family members was 2615.2 CNY (median 500, IQR 250-2025). Factors associated with out-of-pocket costs and productivity losses included hospitalisation, adverse drug reactions, cost of drugs to 'protect' the liver, cost of second-line anti-tuberculosis drugs and diagnostic delay. CONCLUSION: Although the government of China has implemented a 'free TB service policy', the economic burden on patients is still heavy. More patient-centred interventions are essential to reduce the financial burden on patients.

Increased duration of simulated childbirth injuries results in increased time to recovery.

Stress urinary incontinence (SUI) development is strongly correlated with vaginal childbirth, particularly increased duration of the second stage of labor. However, the mechanisms of pelvic floor injury leading to SUI are largely unknown. The aim of this study was to determine the effects of increased duration of vaginal distension (VD) on voiding cystometry, leak point pressure testing, and histology. Sixty-nine virgin female rats underwent VD with an inflated balloon for either 1 or 4 h, while 33 age-matched rats were sham-VD controls. Conscious cystometry, leak point pressure testing, and histopathology were determined 4 days, 10 days, and 6 wk after VD. The increase in abdominal pressure to leakage (LPP) during leak point pressure testing was significantly decreased in both distension groups 4 days after distension, indicative of short-term decreased urethral resistance. Ten days after VD, LPP was significantly decreased in the 4-h but not the 1-h distension group, indicating that a longer recovery time is needed after longer distension duration. Six weeks after VD, LPP was not significantly different from sham-VD values, indicating a return toward normal urethral resistance. In contrast, 6 wk after VD of either duration, the distended rats had not undergone the same increase in voided volume as the sham-VD group, suggesting that some effects of VD do not resolve within 6 wk. Both VD groups demonstrated histopathological evidence of acute injuries and tissue remodeling. In conclusion, this experiment suggests pressure-induced hypoxia as a possible mechanism of injury in vaginal delivery.

Long-term follow-up study on the Maquet procedure with special reference to the causes of failure.

Thirty-nine patients with symptomatic osteoarthrosis (OA) of the patellofemoral joint were treated with 42 anterior tibial tubercle elevations, also known as the Maquet procedure. The patients all had symptomatic OA of the patellofemoral joint that fell into one of three categories: old patellar fracture, chronic patellar subluxation, or postpatellectomy pain. In the latter group, the OA was manifested by erosions of trochlear articular cartilage from the articulating quadriceps tendon-patellar ligament suture line. All 39 patients had a 1.5-2.5-cm tibial tubercle elevation with medial displacement, as necessary, to centralize their patellofemoral mechanisms. Follow-up period averaged 6.1 years. Seventy-nine percent (33 of 42 procedures) had good to excellent results. There was a major complication rate of 7%. Six of the nine failures were attributable to social/psychiatric reasons. Previously unrecognized tibiofemoral OA was the reason for poor results in two of the other failures, and one failure was unexplained. Patients with long-standing symptoms caused by patellofemoral OA should preoperatively be psychologically evaluated and diagnostically arthroscoped before the Maquet procedure is carried out.

A two-level cross-sectional model using grafted polynomials.

A new statistical model is proposed for the analysis of hierarchically structured cross-sectional growth data, especially for where measurements are made over long age ranges. The model combines a two-level model with grafted piecewise polynomials, to make efficient use of available data.

Non-parametric estimation of age-related centiles over wide age ranges.

A new method for estimating age-related centile curves has been developed, which is suitable for measurement covering a wide age range. The method was used to calculate weight centile curves of 8995 children from birth to 6 years obtained by the Collaborating Centre for Physical Growth and Psychosocial Development of Children in Shanghai, China.