Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

OBJECTIVETo investigate the chromosomal aberration in sporadic colorectal carcinoma and its association with clinicopathological features.

METHODSComparative genomic hybridization(CGH) was used to screen the changes in the number of DNA sequence copies in 40 sporadic colorectal cancer patients in order to identify regions that contain genes important for the development and progression of colorectal cancer.

RESULTSIn 40 sporadic colorectal cancer, frequent gain at 20 q, 12 q, 13 q, 7 p, 7 q and 16 q were found, while loss was also found at 18 q, 5 q, 4 q, 8 pand 17 p. The number of chromosomal aberration was closely associated with tumor stage(P<0.05). No significant association was found between the number of chromosomal aberration and tumor site, histopathologic type and histologic grade.

CONCLUSIONSChromosomal aberration exists generally in sporadic colorectal carcinoma. The number of chromosomal aberration and gain of 20q are closely associated with tumor stage.

Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations ; Chromosome Mapping ; Colorectal Neoplasms ; genetics ; pathology ; Comparative Genomic Hybridization ; DNA Probes ; Female ; Gene Dosage ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis

BACKGROUNDToll like receptor (TLR) 9 has been shown to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) in animal models. Its pathogenic role in human SLE, however, was poorly elucidated. This study was performed to investigate the role of TLR9 involved in the aberrant signaling pathway and its correlation with disease activity in SLE.

METHODSmRNA level of TLR9 and interferon (IFN) regulatory factor 5 (IRF5) in peripheral blood mononuclear cells (PBMCs) were determined by real-time polymerase chain reaction (PCR). IFN-a expression was measured in the serum of the SLE patients by enzyme-linked immunosorbent assay (ELISA).

RESULTSTLR9 expression was significantly higher in SLE patients than that in health controls (P = 0.011). SLE patients with positive anti-dsDNA antibody had significantly higher expression of TLR9 than that with negative anti-dsDNA antibody (P = 0.001). TLR9 expression was positively correlated with fever (P = 0.017), alopecia (P = 0.046), safety of estrogens in lupus erythematosus national assessment SLE disease activity index (SELENA-SLEDAI) score (r(s) = 0.385, P = 0.003), and the level of IRF5 (r(s) = 0.35, P = 0.027) and IFN-a (r(s) = 0.627, P = 0.001) in SLE patients.

CONCLUSIONTLR9 is associated with SLE disease activity and might be involved in the IFN-a pathway of SLE.

Adolescent ; Adult ; Antibodies, Antinuclear ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interferon Regulatory Factors ; metabolism ; Interferon-alpha ; blood ; Leukocytes, Mononuclear ; metabolism ; Lupus Erythematosus, Systemic ; blood ; genetics ; metabolism ; Male ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Toll-Like Receptor 9 ; genetics ; metabolism ; Young Adult

BACKGROUNDInfants in some areas of China developed urinary lithiasis after being fed with powdered milk that was tainted with melamine in 2008 and very small proportion of the infants developed acute renal failure caused by urinary tract calculus obstruction. The aim of this article was to summarize clinical characteristics, diagnosis and treatment of infants with urinary calculus and acute renal failure developed after being fed with melamine tainted formula milk.

METHODSData of infant patients with urinary calculus and acute renal failure due to melamine tainted formula milk admitted to the Beijing Children's Hospital Affiliated to the Capital Medical University and the Xuzhou Children's Hospital in 2008 were used to analyze the epidemiological characteristics, clinical manifestations, imaging features as well as effects of 4 types of therapies.

RESULTSAll the 34 infants with urinary calculus were complicated with acute renal failure, their blood urea nitrogen (BUN) was (24.1+/-8.2) mmol/L and creatinine (Cr) was (384.2+/-201.2) micromol/L. The chemical analysis on the urinary calculus sampled from 15 of the infants showed that the calculus contained melamine and acidum uricum. The time needed for the four types of therapies for returning Cr to normal was (3.5+/-1.9) days for cystoscopy group, (2.7+/-1.1) days for lithotomy group, (3.8+/-2.3) days for dialysis group, and (2.7+/-1.6) days for medical treatment group, which had no statistically significant difference (P=0.508). Renal failure of all the 34 infants was relieved within 1 to 7 days, averaging (3.00+/-1.78) days.

CONCLUSIONSMelamine tainted formula milk may cause urinary calculus and obstructive acute renal failure. It is suggested that firstly the patients with urinary calculus complicated with acute renal failure should be treated with dialysis or medication to correct electrolyte disturbance, in particular hyperkalemia, and then relieve the obstruction with available medical and surgical methods as soon as possible. It was observed that the short-term prognosis was satisfactory.

Acute Kidney Injury ; diagnosis ; etiology ; pathology ; therapy ; Child, Preschool ; Cystoscopy ; Female ; Humans ; Infant ; Male ; Peritoneal Dialysis ; Retrospective Studies ; Treatment Outcome ; Triazines ; poisoning ; Urinary Calculi ; complications ; diagnosis ; pathology ; therapy

BACKGROUNDComputed tomography (CT) is better than routine magnetic resonance imaging (MRI) in detecting intracranial calcification. This study aimed to assess the value of MR susceptibility weighted imaging (SWI) in the detection and differentiation of intracranial calcification and hemorrhage.

METHODSEnrolled in this study were 35 patients including 13 cases of calcification demonstrated by CT and 22 cases of intracerebral hemorrhage. MR sequences used in all the subjects included axial T1WI, T2WI and SWI. The phase shift (PS) of calcification and hemorrhage on SWI was calculated and their signal features on corrected phase images were compared. The sensitivity of T1WI, T2WI and SWI in detecting intracranial calcification and hemorrhage was analyzed statistically.

RESULTSThe detection rate of SWI for cranial calcification was 98.2%, significantly higher than that of T1WI and T2WI. It was not significantly different from that of CT (P > 0.05). There were 49 hemorrhagic lesions at different stages detected on SWI, 30 on T2WI and 18 on T1WI. The average PS of calcification and hemorrhage was +0.734 +/- 0.073 and -0.112 +/- 0.032 respectively (P < 0.05). The PS of calcification was positive and presented as a high signal or the mixed signal dominated by a high signal on the corrected phase images, whereas the PS of hemorrhage was negative and presented as a low signal or the mixed signal dominated by a low signal.

CONCLUSIONSSWI can accurately demonstrate intracranial calcification, not dependant on CT. Being more sensitive than routine MRI in detecting micro-hemorrhage, SWI may play an important role in differentiating cerebral diseases associated with calcification or hemorrhage.

Adolescent ; Adult ; Aged ; Brain Diseases ; diagnosis ; Calcinosis ; diagnosis ; Cerebral Hemorrhage ; diagnosis ; Child ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged

OBJECTIVETo summarize clinical characteristics, diagnosis and treatment of infants with urinary calculus and acute renal failure developed after being fed with melamine tainted formula milk.

METHODSData of infant patients with urinary calculus and acute renal failure due to melamine tainted formula milk admitted to the Beijing Children's Hospital affiliated to the Capital Medical University and the Xuzhou Children's Hospital in 2008 were used to analyze the epidemiological characteristics, clinical manifestations, image features as well as effects of 4 types of therapies.

RESULTSAll the 34 infants with urinary calculus were complicated with acute renal failure, their blood urea nitrogen (BUN) was (24.1 +/- 8.2) mmol/L and creatinine (Cr) was (384.2 +/- 201.2) micromol/L. The chemical analysis on the urinary calculus sampled from 14 of the infants showed that the calculus contained melamine and acidum uricum. The time needed for the four types of therapies for returning Cr to normal was (3.5 +/- 1.9) d for cystoscopy group, (2.7 +/- 1.1) d for lithotomy group, (3.8 +/- 2.3) d for dialysis group, and (2.7 +/- 1.6) d for medical treatment group, which had no statistically significant difference (P = 0.508). Renal failure of all the 34 infants was relieved within 1 to 7 days, averaging (3.0 +/- 1.8) d.

CONCLUSIONMelamine tainted formula milk may cause urinary calculus and obstructive acute renal failure. It is suggested that firstly the patients with urinary calculus complicated with acute renal failure should be treated with dialysis or medication to correct electrolyte disturbances, in particular hyperkalemia, and then relieve the obstruction with available medical and surgical methods as soon as possible. It is observed that the short term prognosis is satisfactory.

Acute Kidney Injury ; diagnosis ; epidemiology ; therapy ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant Food ; Male ; Triazines ; toxicity ; Urinary Calculi ; diagnosis ; epidemiology ; therapy

The coronavirus disease 2019(COVID-19) is developing rapidly and posing great threat to public health. There is no effective intervention for the severe patients, and their prognosis is poor. It is worth noting that in the fight against COVID-19, China has always put equal emphasis on both Chinese and Western medicine. Traditional Chinese medicine has played an important role in the whole process. It is of great significance to discuss the rules and characteristics of the prescription of traditional Chinese medicine in the treatment of COVID-19. In this study, information was collected from 444 severe COVID-19 patients who were admitted to a hospital designated to treat patients with severe COVID-19 in Wuhan before March 20, 2020. We collected traditional Chinese medicine prescriptions for patients with severe COVID-19, referred to Chinese Pharmacopoeia to standardize the names of traditional Chinese medicine, and extract the property, flavor and channel tropism of traditional Chinese medicines to analyze the rules of the prescriptions. IBM SPSS Modeler 18.0 software was used to conduct correlation analysis of traditional Chinese medicine. Effective traditional Chinese medicines against COVID-19 was identified by the TCMATCOV platform. In the end, 1 532 effective prescriptions were included. Among them, the high-frequency drugs are Poria, Astragali Radix, Pogostemonis Herba, Armeniacae Semen Amarum, Atractylodis Macrocephalae Rhizoma, Pinelliae Rhizoma, Glycyrrhizae Radix et Rhizoma, Magnoliae Officinalis Cortex, Ephedrae Herba, Cinna-momi Ramulus. Most of the drugs have the following functions: resolving dampness, replenishing deficiency, resolving phlegm, cough, and asthma. The core combinations are Pogostemonis Herba-Poria, Astragali Radix-Pogostemonis Herba-Poria, Amomi Fructus-Poria, Amomi Fructus-Pogostemonis Herba, Amomi Fructus-Astragali Radix. The majority of the medicines are with cold and warm properties, and the proportions are 41.03% and 38.46%, respectively. The medicinal flavors are mainly concentrated in sweet and bitter, and the proportions are 34.71% and 30.58%, respectively. The meridian of the drug is more into the lung, stomach and spleen, with lung accounting for 22.87%. From the analysis of high-frequency drugs to the core combinations, one can see that the main treatment principle for severe COVID-19 is to remove internal and external dampness, protect the spleen and stomach, remove evil energy, and support righteousness. TCMATCOV platform was used to calculate the network disturbances of the high-frequency drugs. It was found that the traditional Chinese medicine with a high disturbance score accounted for a high proportion of the classic anti-COVID-19 prescriptions used by clinicians. Among them, the drugs with top scores are Ephedrae Herba, Citri Reticulatae Pericarpium, Eupatorii Herba, Platycodonis Radix, Cinnamomi Ramulus, Astragali Radix, Magnoliae Officinalis Cortex, Atractylodis Macrocephalae Rhizoma, Pogostemonis Herba, Scutellariae Radix. After a further exploration of the action targets, it was showed that disease-specific factor TNF was the target of the above ten drugs, and traditional Chinese medicine can exert anti-inflammatory and immune-modulating effects.
Betacoronavirus ; China ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; drug therapy

OBJECTIVE: To investigate the clinical characteristics, the medicine application and to evaluate the disease activity in patients with osteoarthritis (OA) in China. METHODS: This was a cross-sectional study. Totally 1 066 cases of OA from 40 hospitals in China from April to October 2017 were retrospectively enrolled. Demographic characteristics, clinical data, medicine application, and joint function were evaluated. All the data were analyzed by SPSS software 19.0. t test, Mann-Whitney U test and chi-square test were used for statistical analysis. RESULTS: In the 1 066 cases, the male-to-female ratio was 1:3.6 and the average age was (61.9±11.0) years, with an age range from 36 to 94 years. The incidence of knee OA, hip OA, and hand OA were respectively 81.9% (873/1 066), 14.1% (150/1 066), and 36.3% (387/1 066). In the study, 242 (22.7%) cases had two kinds of joint areas involved and three joint areas were involved in 51 cases (4.8%), and 56.6% (603/1 066) of the patients used more than one kind of non-steroid anti-inflammatory drugs (NSAIDs) while 61.2% (652/1 066) used disease modifying osteoarthritis drugs (DMOADs), including glucosamine (37.5%, 400/1 066), chondroitin sulfate (2.0%, 21/1 066), diacetate (5.9%, 63/1 066), and the combination of these drugs (15.8%, 168/1 066). 8.6% (92/1 066) patients only took analgesics to relieve the pain, not using any kind of NSAIDs or DMOADs. And 232 patients (21.7%) had intra-articular injections, including 9.2% (98/1 066) sodium hyaluronate, 4.5%(48/1 066) glucocorticoid, and 8.1% (86/1 066) combination of the two drugs. The proportion of the patients taking topical drugs accounted for 26.5% (283/1 066) and physical therapy accounted for 15.8% (168/1 066). Compared with those who suffered from knee OA, the patients who suffered from hip OA had more severe disease assessment. Moreover, there were significant differences in pain (Z=-7.625, P<0.001), morning stiffness (Z=-6.229, P<0.001), and joint function (Z=-6.777, P<0.001) between the two groups of the patients who suffered from knee or hip OA with The Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. Furthermore, patients with hip OA took more analgesics (χ²=24.838, P<0.001). CONCLUSION Oral NSAIDs and DMOADs are wildly used in patients with OA in China. However, the treatment of some patients still need to be improved. Patients with hip OA are more seriously ill and require aggressive treatment.
Adult ; Aged ; Aged, 80 and over ; China ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Hip/drug therapy* ; Osteoarthritis, Knee/drug therapy* ; Practice Patterns, Physicians'/statistics & numerical data* ; Retrospective Studies ; Surveys and Questionnaires