Viral shedding pattern of severe fever with thrombocytopenia syndrome virus in severely ill patients: A prospective, Multicenter cohort study.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is spreading rapidly in Asia. The pathway of SFTS virus shedding from patient and specific use of personal protective equipments (PPEs) against viral transmission have rarely been reported. The study was to determine SFTS virus (SFTSV) shedding pattern from the respiratory, digestive and urinary tract to outside in patients. Methods: Patients were divided into mild and severe groups in three sentinel hospitals for SFTS in Anhui province from April 2020 to October 2022. SFTSV level from blood, throat swabs, fecal/anal swabs, urine and bedside environment swabs of SFTS patients were detected by qRT-PCR. Specific PPEs were applied in healthcare workers contacting with the patients who had oropharyngeal virus shedding and hemorrhagic signs. Results: A total of 189 SFTSV-confirmed patients were included in the study, 54 patients died (case fatality rate, 28.57 %). Positive SFTSV in throat swabs (T-SFTSV), fecal/anal swabs (F-SFTSV) and urine (U-SFTSV) were detected in 121 (64.02 %), 91 (48.15 %) and 65 (34.4 %) severely ill patients, respectively. The levels of T-SFTSV, F-SFTSV and U-SFTSV were positively correlated with the load of SFTSV in blood. We firstly revealed that SFTSV positive rate of throat swabs were correlated with occurrence of pneumonia and case fatality rate of patients (P < 0.0001). Specific precaution measures were applied by healthcare workers in participating cardiopulmonary resuscitation and orotracheal intubation for severely ill patients with positive T-SFTSV, no event of SFTSV human-to-human transmission occurred after application of effective PPEs. Conclusions: Our research demonstrated SFTSV could shed out from blood, oropharynx, feces and urine in severely ill patients. The excretion of SFTSV from these parts was positively correlated with viral load in the blood. Effective prevention measures against SFTSV human-to-human transmission are needed.

Increase in the Prevalence of Resistance Determinants to Trimethoprim/Sulfamethoxazole in Clinical Stenotrophomonas maltophilia Isolates in China.

AIMS: This study was carried to reveal the genetic mechanisms of trimethoprim/sulfamethoxazole (SXT) resistance. METHODS: Among 300 clinical Stenotrophomonas maltophilia isolates from China, resistance determinants such as sul and dfrA genes, integrons and transposase were examined using PCR, DNA sequencing and thermal asymmetric interlaced PCR (TAIL-PCR). Data were analyzed using SPSS 20.0. RESULTS: Of the 300 isolates, 116 (38.7%) were resistant to SXT. An alarming trend of increased resistance to SXT were found over the 10-year period. The positive rates of sul and class 1 integrase (intI1) increased gradually with the development of SXT resistance over the 10-year period. Multiple logistic regression analyses indicated that the genes of qacEΔ1-sul1 (81% vs 46.2%, p = 0.000), sul2 (50.9% vs 9.8%, p = 0.000), intI1 (83.6% vs 65.8%, p = 0.000), dfrA12 (25% vs 3.3%, p = 0.000), dfrA17 (15.5% vs 3.8%, p = 0.000) and dfrA27 (4.3% vs 1.6%, p = 0.01) were more prevalent in SXT-resistant isolates than SXT-susceptible isolates except dfrA1(p = 0.83) and dfrA5(p = 0.18). Sequencing data revealed 12 types of resistance gene cassettes (aar-3-dfrA27, dfrA12-aadA2, dfrA17-aadA5, cmlA1, aacA4, aadA5, arr-3-aacA4, aadA1, aadB-aadA4, aacA4-catB8-aadA1, aadB-aac(6')-II-blaCARB-8 and aac(6')-II-blaCARB-8) located in the class 1 integron in 163 isolates (87% SXT-resistant vs 33.7% SXT-susceptible isolates, p = 0.000). A novel finding was the aar-3-dfrA27 (KC748137) gene cassette. The gene of sul2 linked to transposase in 50 SXT- resistant and 7 SXT- susceptible isolates was detected by TAIL-PCR. CONCLUSIONS: The findings demonstrated a higher prevalence of sul, dfrA, intI1 and resistance gene cassettes in class 1 integron in SXT-resistant clinical S. maltophilia isolates in China. The sul1 and dfrA genes located in integrons and the sul2 linked to transposase may imply wide and rapid dissemination of resistance gene in bacteria.

Gastrin acting on the cholecystokinin2 receptor induces cyclooxygenase-2 expression through JAK2/STAT3/PI3K/Akt pathway in human gastric cancer cells.

Gastrin, cholecystokinin2 receptor (CCK2R), and cyclooxygenase-2 (COX-2) have been implicated in the carcinogenesis and progression of gastric cancer. Our study demonstrated that antagonist or siRNA against CCK2R blocked amidated gastrin (G17)-induced activation of STAT3 and Akt in gastric cancer cell lines. G17-increased COX-2 expression and cell proliferation were effectively blocked by CCK2R antagonist and inhibitors of JAK2 and PI3K. In addition, knockdown of STAT3 expression significantly attenuated G17-induced PI3K/Akt activation, COX-2 expression, and cell proliferation. These results suggest that CCK2R-mediated COX-2 up-regulation via JAK2/STAT3/PI3K/Akt pathway is involved in the proliferative effect of G17 on human gastric cancer cells.

Downregulation of miR-101 in gastric cancer correlates with cyclooxygenase-2 overexpression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. It has been demonstrated that COX-2 overexpression depends on different cellular pathways, involving both transcriptional and post-transcriptional regulation. MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators. Here, we characterize miR-101 expression and its role in the regulation of COX-2 expression, which in turn, will provide us with additional insights into the potential therapeutic benefits of exogenous miR-101 for treatment of gastric cancer. Our results showed that miR-101 levels in gastric cancer tissues were significantly lower than those in the matched normal tissue (P < 0.01). Furthermore, lower levels of miR-101 were associated with increased tumor invasion and lymph node metastasis (P < 0.05). We also found an inverse correlation between miR-101 and COX-2 expression in both gastric cancer specimens and cell lines. Significant decreases in COX-2 mRNA and COX-2 levels were observed in the pre-miR-101-infected gastric cancer cells. One possible mechanism of interaction is that miR-101 inhibited COX-2 expression by directly binding to the 3'-UTR of COX-2 mRNA. Overexpression of miR-101 in gastric cancer cell lines also inhibited cell proliferation and induced apoptosis in vitro, as well as inhibiting tumor growth in vivo. These results collectively indicate that miR-101 may function as a tumor suppressor in gastric cancer, with COX-2 as a direct target.

Effect of Mn-Zn ferrite on apatite-wollastonite glass-ceramic (A-W GC).

Magnetic bioactive glass-ceramics (M GC) were prepared by doping apatite-wollastonite glass-ceramic (A-W GC) with Mn-Zn ferrite. The effect of different contents of Mn-Zn ferrite on the phase structure, magnetic property and bioactivity of A-W GC was investigated. X-ray powder diffraction results showed that A-W GC exhibited apatite, fluorapatite and wollastonite as the main phases. The doping of Mn-Zn ferrite caused the formation of a new phase Zn(0.75)Mn(0.75)Fe(1.5)O(4) in M GC. The amount of this new phase increased with increasing content of Mn-Zn ferrite. Under a magnetic field of 7.96 x 10(5) A m(-1), the saturation magnetization of M GC increased from 4.63 to 9.7 A m(2) kg(-1), but the coercive forces of M GC decreased from 2.39 x 10(4) to 7.56 x 10(3) A m(-1) as the Mn-Zn ferrite content increased from 5% to 20% in the material. The bioactivity of samples was evaluated by soaking in simulated body fluid (SBF). The results showed that the doping of Mn-Zn ferrite decreased the bioactivity of A-W GC dramatically. It took 7 days for an apatite layer to form on the surface of A-W GC, while at least 30 days was needed for an apatite layer forming on the surface of M GC.

Inhibition of COX-2 and activation of peroxisome proliferator-activated receptor gamma synergistically inhibits proliferation and induces apoptosis of human pancreatic carcinoma cells.

Although inhibition of cyclooxygenase-2 (COX-2) or activation of peroxisome proliferators-activated receptor gamma (PPAR-gamma) leads to growth inhibition in malignancies, the synergistic anti-tumor effects of combination of COX-2 inhibitor (NS-398) and PPAR-gamma agonist (rosiglitazone) on the human pancreatic cancer cells remains unknown. Here, we evaluated the effects of NS-398 and/or rosiglitazone on the cell proliferation and apoptosis in a pancreatic cancer cell line, SW1990. NS-398 and rosiglitazone decreased cell proliferation in a dose- and time-dependent manner. Proliferating cell nuclear antigen (PCNA) labeling index significantly decreased in the cells treated with either NS-398 or rosiglitazone. Both NS-398 and rosiglitazone alone induced apoptotic cell death of SW1990. The combination of NS-398 and rosiglitazone exerted synergistic effects on proliferation inhibition, and apoptosis induction in SW1990 cells, with down-regulation of Bcl-2 and up-regulation of Bax expression. Our results indicate that simultaneous targeting of COX-2 and PPAR-gamma inhibits pancreatic cancer development more effectively than targeting each molecule alone.

Blockade of cholecystokinin-2 receptor and cyclooxygenase-2 synergistically induces cell apoptosis, and inhibits the proliferation of human gastric cancer cells in vitro.

Gastrin and cyclooxygenase-2 (COX-2) play important roles in the carcinogenesis and progression of gastric cancer. However, it remains unknown whether the combination of cholecystokinin-2 (CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer. Here, we demonstrated that the combination of AG-041R (a CCK-2 receptor antagonist) plus NS-398 (a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition, apoptosis induction, down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells. These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.

4,4-Dichloro-tricyclo-[5.4.0.0]undeca-7,9,11-triene.

The title compound, C(11)H(10)Cl(2), is a useful inter-mediate for the synthesis of 1H-cyclo-propa[b]naphthalene. Strain in the mol-ecule is evidenced by the fact that the cyclo-hexane ring is essentially planar and nearly coplanar with the benzene ring [dihedral angle 1.87 (18)°], and the cyclo-propyl ring is almost perpendicular to the cyclo-hexane ring [dihedral angle 70.99 (12)°]. The mol-ecules are loosely connected into one-dimensional chains by inter-molecular Cl⋯Cl inter-actions with a distance of 3.571 (1) Å. The centroid-to-centroid distance between stacked benzene rings is ca 5.89 Å, indicating that no π-π stacking exists in the crystal structure.

[Studies on the spatial distribution and environmental factors of highly pathogenic avian influenza in Mainland China, using geographic information system technology].

OBJECTIVE: To analyze the spatial distribution of highly pathogenic avian influenza (HPAI) and to explore environmental factors associated with HPAI using geographic information system (GIS) techniques in Mainland China. METHODS: Databases were set up using the information of HPAI during epidemics in 2004, and linked to digital maps at provincial and county administrative layers in the country through the ArcGIS 8.3 software. Spatial cluster analyses, spatial statistics analyses and tracking analyses on epidemic situation of HPAI were implemented. Environmental factors associated with HPAI were also analyzed on data related to weather, vegetation and migratory birds etc. RESULTS: Findings from spatial cluster analyses showed that high incidence area was centralized in 113.261 degrees ordm; east longitude and 23. 119 degrees ordm; north latitude with a radius of 1090.52 kilometers (relative risk= 2.646, P value= 0.001). Spatial statistical analyses showed that HPAI took place mainly in capital cities of provinces and surrounding areas as well as in the circumference areas of arterial rivers, lakes and seacoasts. Results also showed that HPAI occurrences were associated with low air temperature, high relative humidity and high air pressure as well as with east & central migration routes of migratory birds. The average normalized difference vegetation index was 0.36 +/- 0.11 in epidemic areas of HPAI. CONCLUSION: HPAI was unrandomly distributed and geographically clustered in China.

Inhibition of CYP 1A2-dependent MROD activity in rat liver microsomes: an explanation of the hepatic sequestration of a limited subset of halogenated aromatic hydrocarbons.

Many classes of halogenated aromatic compounds (HACs) are highly lipophilic environmental contaminants that exert toxic effects via the Ah receptor signal transduction pathway and whose metabolism generally involves monooxygenase enzymes of the CYP 1A family. Despite their lipophilicity, a high proportion of the body burden of certain polychlorinated dibenzo-p-dioxins and coplanar polychlorinated biphenyls is sequestered in liver, a process believed to involve CYP 1A2. In this work we examined HAC-induced inhibition of the demethylation of 7-methoxyresorufin, a process that is selectively catalyzed by CYP 1A2. 2,3,7,8-Tetrachlorodibenzo-p-dioxin, 3,3',4,4'-tetrachlorobiphenyl (PCB 77) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) were found to be strong competitive inhibitors of methoxyresorufin-O-demethylase activity, consistent with the high ability of hepatic tissue to sequester these compounds selectively.