Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes, and multi-target drugs provide a promising therapy idea for the treatment of cancer. Natural products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic drugs. In this paper, 50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database, and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first time. Through the multi-target anti-cancer prediction system, some dominant fragments that act on multiple tumor-related targets were analyzed, which could be helpful in designing multi-target anti-cancer drugs. Anti-cancer traditional Chinese medicine (TCM) and its natural products were collected to form a TCM formula-based natural products library, and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction system. As a result, alkaloids, flavonoids and terpenoids were predicted to act on multiple tumor-related targets. The predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological experiments. In conclusion, the multi-target anti-cancer prediction system is very effective and reliable, and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer drugs. The anti-cancer natural compounds found in this paper will lay important information for further study.
Antineoplastic Agents/pharmacology* ; Bayes Theorem ; Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional ; Neoplasms/drug therapy*

Objective:To explore the risk factors of abdominal hemorrhage (AH) in patients with severe acute pancreatitis (SAP) and its impact on outcome.Methods:The clinical data of 231 SAP patients admitted to Diagnosis and Treatment Center for SAP of Guizhou Province from January 1, 2015 to December 31, 2019 were retrospectively analyzed. These patients were divided into AH group and non-AH group. The general information, etiology, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, organ failure, complications, interventions, bleeding time, bleeding site and outcome were compared between the two groups. Binary multivariate Logistic regression analysis was used to explore the risk factors of AH in SAP patients and whether the time and location of AH were risk factors affecting the outcome.Results:A total of 231 patients were enrolled in the analysis, including 198 patients without AH and 33 with AH (14.3%). There was no significant difference in gender, age or etiology between the two groups. The scores of APACHE Ⅱ and SOFA in AH group were significantly higher than those in non-AH group [APACHE Ⅱ score: 18 (12, 24) vs. 13 (9, 19), SOFA score: 9 (5, 15) vs. 5 (4, 11), both P < 0.01]. The incidences of acute kidney injury (AKI), gastrointestinal dysfunction, coagulation disorders, necrotic infection, pseudocyst and gastrointestinal fistula in AH group were significantly higher than those in non-AH group (66.7% vs. 47.0%, 36.4% vs. 7.1%, 18.2% vs. 6.6%, 66.7% vs. 9.1%, 66.7% vs. 34.3%, 9.1% vs. 1.5%, all P < 0.05). The proportions of requiring mechanical ventilation (MV) and surgical intervention in AH group were significantly higher than those in non-AH group (69.7% vs. 43.4, 48.5% vs. 14.6%, both P < 0.01). The length of intensive care unit (ICU) stay and hospital stay in AH group were significantly longer than those in non-AH group [length of ICU stay (days): 13 (8, 19) vs. 7 (3, 16), length of hospital stay: 24 (13, 40) vs. 17 (12, 24), both P < 0.01], and the hospital mortality was significantly higher (60.6% vs. 9.6%, P < 0.01). Multivariate Logistic regression analysis showed that APACHE Ⅱ score [odds ratio ( OR) = 1.157, 95% confidence interval (95% CI) was 1.030-1.299, P = 0.014], infectious necrosis ( OR = 12.211, 95% CI was 4.063-36.697, P < 0.01), pseudocyst ( OR = 3.568, 95% CI was 1.238-10.283, P = 0.019) and requiring MV ( OR = 0.089, 95% CI was 1.354-6.625, P = 0.007) were the risk factors of AH in SAP patients. In 33 AH patients, there was no significant difference in hospital mortality between early hemorrhage (occurred within 2 weeks of onset) and late hemorrhage (occurred 2 weeks after onset) groups [66.7% (8/12) vs. 57.1% (12/21), P > 0.05]. All 4 patients in the unspecified bleeding site group died during hospitalization; half or more patients died in the pseudocyst/abscess bleeding (14 cases), mesenteric/intestinal bleeding (13 cases) and gastric variceal bleeding (2 cases) groups (7 cases, 8 cases and 1 case respectively), and there were significant differences among the groups ( P < 0.05). Multivariate Logistic regression analysis showed that neither bleeding time ( OR = 0.989, 95% CI was 0.951-1.028, P = 0.574) nor bleeding site ( OR = 2.009, 95% CI was 0.822-4.907, P = 0.126) was the risk factor of death in patients with SAP combined with AH. Conclusions:Both early and late bleeding significantly increased the length of hospital stay and mortality of SAP patients. APACHE Ⅱ score, infectious necrosis and pseudocyst were the risk factors of AH in SAP patients. Neither bleeding time nor bleeding site was the risk factors of death in patients with SAP combined with AH. However, it still needed to be confirmed by a large sample clinical study.

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

A new variant of concern for SARS-CoV-2,Omicron(B.1.1.529),was designated by the World Health Organization on November 26,2021.This study analyzed the viral genome sequenc-ing data of 108 samples collected from patients infected with Omicron.First,we found that the enrichment efficiency of viral nucleic acids was reduced due to mutations in the region where the primers anneal to.Second,the Omicron variant possesses an excessive number of mutations compared to other variants circulating at the same time(median:62 vs.45),especially in the Spike gene.Mutations in the Spike gene confer alterations in 32 amino acid residues,more than those observed in other SARS-CoV-2 variants.Moreover,a large number of nonsynonymous mutations occur in the codons for the amino acid residues located on the surface of the Spike protein,which could potentially affect the replication,infectivity,and antigenicity of SARS-CoV-2.Third,there are 53 mutations between the Omicron variant and its closest sequences available in public databases.Many of these mutations were rarely observed in public databases and had a low muta-tion rate.In addition,the linkage disequilibrium between these mutations was low,with a limited number of mutations concurrently observed in the same genome,suggesting that the Omicron vari-ant would be in a different evolutionary branch from the currently prevalent variants.To improve our ability to detect and track the source of new variants rapidly,it is imperative to further strengthen genomic surveillance and data sharing globally in a timely manner.

BACKGROUND: Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA. METHODS: Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48. RESULTS: At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed. CONCLUSIONS: This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted. TRIAL REGISTRATION Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.
Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; China ; Diphosphonates ; Double-Blind Method ; Drug Therapy, Combination ; Humans ; Methotrexate/therapeutic use* ; Technetium/therapeutic use* ; Treatment Outcome

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

Objective To compare the clinical efficacy and safety of docetaxel combined with carboplatin (TP) and epirubicin combined with cyclophosphamide sequential docetaxel (EC-T) adjuvant in the treatment of three negative breast cancer in phase III . Methods 62 cases of three negative breast cancer patients in phase III from May 2012 to October 2016 were selected and randomly divided into the control group and the experimental group, with 31 patients in each group. The control group was treated with epirubicin combined with cyclophosphamide and sequential docetaxel, and the experimental group was treated with docetaxel and carboplatin. The clinical indicators were compared and analyzed. Results There was no significant difference in the recent remission rate (77.42%) between the experimental group and the control group (74.19%). Two groups of patients with adverse reactions were restored within one month. There were 10 cases of WBC decrease in the experimental group, with the incidence rate of 32.25%. There were 18 cases of WBC decrease in the control group, the incidence rate was 58.06%, the difference was statistically significant (P<0.05). Conclusion Docetaxel combined with carboplatin and epirubicin adjuvant combined with cyclophosphamide than star sequential docetaxel in the treatment of three patients with negative breast cancer stage III were tolerated, TP occurred leukopenia and alopecia with low probability.

Objective To establish an anxiety-like gastric hypersensitivity ( GHS) rat model of functional dyspep-sia induced by new sequential stress. Methods Twenty-six male 1-day-old Sprague-Dawley rat pups were randomly di-vided into control and model groups ( n=13 in each group) . The model rats received sequential stress from postnatal day 2:neonatal maternal separation (NMS), acute gastric irritation (AGI) and restraint stress (RS). The control rats were reared freely with their mothers without undergoing the sequential stress. From postnatal 8th week all rats started to receive elevated plus maze ( EPM ) , open field test ( OF ) , abdominal withdrawal reflex ( AWR ) and electromyographic test ( EMG) . Results EPM and OF experiments depicted that the model rats showed obvious anxiety-like behavior ( P<0. 05 or P<0. 01). AWR and EMG tests exhibited that the model rats had elevated gastric hypersensitivity to gastric distention (P<0. 05 or P<0. 01). Conclusions An anxiety-like GHS rat model of functional dyspepsia can be successfully estab-lished with our new method of sequential stress.

Objective To investigate the epidemiologic characteristics of patients with severe acute pancreatitis (SAP) and the effects of its complications on prognoses in past 7 years in the north area of Guizhou province. Methods Data of 209 patients with SAP admitted to the Department of Critical Care Medicine of Affiliated Hospital of Zunyi Medical College from January 2009 to January2016 were retrospectively analyzed, and they were divided into a survival group (178 cases) and a death group (31 cases) according to the prognosis. The gender, age, diagnosis (primary and recurrent), the length of stay in hospital, the levels of creatinine and total bilirubin (TBil), the time of blood purification, hematocrit (HCT) level on the first day after admission, pathogenesis, complications [infection, pseudocyst, intra-peritoneal hemorrhage, acute renal failure (ARF), acute respiratory distress syndrome (ARDS), abdominal compartment syndrome (ACS), pancreatic encephalopathy, multiple organ dysfunction syndrome (MODS)], sequential organ failure (SOFA) score (maximum SOFA score during hospital stay), application of hormones, surgical interference, etc. related factors were compared, the SAP epidemiological characteristics, factors affecting prognosis and the effect of complications on prognosis in intensive care unit (ICU) were analyzed in the two groups.Results Of the 209 patients 98 cases were diagnosed biliary pancreatitis accounting for the majority (46.9%), hyperlipidemic pancreatitis 76 cases (36.3%), alcoholic pancreatitis 6 cases (2.8%) and idiopathic pancreatitis29 cases (13.9%). The age (years: 47.1±13.5 vs. 53.2±12.0), creatinine (μmol/L: 109.4±100.3 vs. 335.7±222.4), the ration of intra-peritoneal hemorrhage [4.5% (8) vs. 38.7% (12)], ARF [1.1% (2) vs. 54.8% (17)], ACS [1.1% (2) vs. 9.7% (3)], MODS [18.5% (33) vs. 74.2% (23)] and SOFA score (3.3±2.4 vs. 10.5±5.4), percentage of patients using hormones [5.6% (10) vs. 29.0% (9)] were significantly lowered (allP < 0.05) and the time of blood purification was shortened (days: 1.95±1.97 vs. 4.81±5.84) in survival group than those in death group; while the gender, diagnosis, the length of stay in hospital, TBil, HCT on the first day after admission, pathogenesis, complications (infection, pseudocyst, ARDS and pancreatic encephalopathy) and surgical treatment situation were compared between the two groups, no statistical significant differences were seen (allP > 0.05). Logistic regression analysis showed that creatinine > 300μmol/L [odds ratio (OR) was 2.651, 95% confidence interval (95%CI) was 1.459-3.935,P = 0.017], intra-peritoneal hemorrhage (OR was 5.231, 95%CI was 3.517-7.159,P = 0.000), ARF (OR was 3.731, 95%CI was 2.641-4.857,P = 0.000), ACS (OR was 2.517, 95%CI was 1.003-3.098,P = 0.000), use of hormone (OR was 1.012, 95%CI was 0.825-2.051,P = 0.000) and SOFA score (OR was 3.179, 95%CI was 2.630-6.021 andP = 0.000), MODS (OR was 4.716, 95%CI was 2.086-7.902 andP = 0.031) were the risk factors having critical effects on the prognosis of thedisease, The higher the creatinine level, the worse the prognosis. The mortality of ARF was very high reaching 89.5%; the mortalities of patients with complications as intra-peritoneal haemorrhage, ACS, MODS, pancreatic encephalopathy, AKI, infection, pancreatic pseudocyst and ARDS were as follows: 60.0%, 60.0%, 41.1%, 33.3%, 32.1%, 23.1%, 17.7%, 13.1% respectively.Conclusion Biliary disease andhyperlipidemia are the major causes of SAP in north area of Guizhou province, creatinine > 300μmol/L, intra-peritoneal hemorrhage, ARF, ACS, SOFA score, use of hormones are the independent risk factors leading to poor outcome in patients with SAP and the use of hormones cannot ameliorate the disease situation.

OBJECTIVETo explore clinical effects of internal fixation in treating displaced clavicle fracture combined with coracoid process.

METHODSFrom January 2005 to July 2012, 9 patients with displaced clavicle fracture combined with coracoid process were treated by internal fixation. Among them, there were 6 males and 3 females with an average age of 40.1 (ranged from 20 to 57) years old. According to Eyres classification: 3 cases were type II B, 1 case was type II A, 3 cases were type III B, and 2 cases were type V A. All patients had history of injury, and diagnosed as coracoid fracture X-ray and CT before operation. Herscovici criteria was used to evaluate function of shoulders joint after operation.

RESULTSSeven of 9 patients were followed up from 6 to 18 (averaged 11) months. The incisions were healed at stage I, coracoid process obtained bony healing, and reduction of acromioclavicular joint well. According to Herscovici criteria, 6 patients got excellent results and 1 in good.

CONCLUSIONInternal fixation for the treatment of displaced clavicle fracture combined with coracoid process could restore physiological anatomical position of coracoid process, and benefit for recovery of limb function.

Adult ; Clavicle ; injuries ; Female ; Fracture Fixation, Internal ; methods ; Fractures, Bone ; surgery ; Humans ; Male ; Middle Aged ; Recovery of Function ; Scapula ; injuries ; Shoulder Joint ; injuries