AIM:To investigate the effect of dihydroartemisinin ( DHA) adjuvant treatment on enhancing the antitumor effect of 5-fluorouracil (5-FU) against gastric cancer .METHODS:The gastric cancer BGC-823 cells were di-vided into control group , DHA group, 5-FU group, 5-FU+DHA group and 5-FU+DHA+SIRT1 plasmid group.The via-bility of BGC-823 cells treated with DHA and 5-FU was measured by MTT assay .The expression of SIRT1 and NADPH ox-idase, activation of caspase-9 and caspase-3, and phosphorylation of ASK1 and JNK in the BGC-823 cells treated with DHA and 5-FU were determined by Western blot .The production of ROS and the apoptosis of the BGC-823 cells treated with DHA and 5-FU were analyzed by flow cytometry .RESULTS:Dihydroartemisinin significantly inhibited the expression of SIRT1 and increased NADPH oxidase protein level (P<0.05).DHA increased the sensitivity of BGC-823 cells to 5-FU, thus decreasing the IC50 of 5-FU to the gastric cancer cells.However, transfection with SIRT1 plasmid decreased the cytotoxicity of DHA and 5-FU co-treatment to the BGC-823 cells.DHA promoted the production of ROS and phosphoryla-tion of ASK1 and JNK induced by 5-FU in the BGC-823 cells ( P<0.05 ) .However , ROS scavenger N-acetylcysteine ( NAC) or JNK specific inhibitor SP600125 inhibited the cell death and activation of caspase-9 and caspase-3 induced by DHA and 5-FU co-treatment (P<0.05).In addition, NAC significantly inhibited the phosphorylation of JNK in the BGC-823 cells co-treated with DHA and 5-FU.However, treatment with SP600125 did not influence the ROS production in the BGC-823 cells, indicating that JNK was the downstream target of ROS pathway .CONCLUSION: Combination of DHA with 5-FU induces caspase-dependent apoptosis in gastric cancer cells through the SIRT 1/NADPH oxidase/ROS/JNK sig-naling pathway .

OBJECTIVETo investigate the expression of calcyclin in pancreatic carcinoma and its relation to the patients' prognosis.

METHODSHuman pancreatic carcinoma tissue microarray was constructed, which contained 63 cores of 3 normal adult pancreas tissues, 6 chronic pancreatitis tissues, 51 pancreatic carcinoma tissues and 3 islet cell carcinoma tissues. Immunohistochemistry was performed to detect the expression of calcyclin in these tissues, and the relationship between calcyclin and the clinicopatholoical features of pancreatic carcinoma was analyzed.

RESULTSThe positivity rate of calcyclin in the pancreatic carcinoma tissue was 76.5% (39/51), and calcyclin staining was more intense in the malignant cells than in the benign cells (P=0.007), suggesting a correlation between calcyclin expression and pancreatic carcinoma. No evidence was found for an association of calcyclin expression with the variables including the patients' gender, age at surgery, and tumor grade. Weak staining for calcyclin was noted in chronic pancreatitis tissues.

CONCLUSIONCalcyclin expression is related to the pancreatic carcinomas and up-regulation of calcyclin expression is possibly an early event in pancreatic and pragression of development cancer.

Adult ; Aged ; Biomarkers, Tumor ; genetics ; metabolism ; Cell Cycle Proteins ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms ; genetics ; metabolism ; Pancreatitis, Chronic ; genetics ; metabolism ; S100 Calcium Binding Protein A6 ; S100 Proteins ; genetics ; metabolism

OBJECTIVETo assess if the modulating effect of platelet-derived growth factor (PDGF)-BB on p21(WAF1) was mediated by upregulating transforming growth factor (TGF)-beta(1) expression in vascular smooth muscle cells (VSMC).

METHODSTGF-beta(1) mRNA and protein expressions were measured by reverse transcription-PCR and ELISA, the protein expressions of p21(WAF1) and the downstream TGF-beta signalling including TGF-beta type I receptor (ALK-5 in VSMC), Smurf2, pSmad2/3, Smad4, Smad7 were detected by Western blot.

RESULTSPDGF-BB significantly upregulated the expressions of TGF-beta(1) at mRNA (0.79-fold) and protein (1.98-fold) levels in VSMC, significantly inhibited the expression of p21(WAF1) (-67 +/- 12)%, and enhanced the expressions of ALK-5, pSmad2/3, Smad4, Smurf2 protein by 1.21-fold, 0.95-fold, 0.69-fold and 2.55-fold respectively, inhibited Smad7 expression (-65 +/- 9)%, these alterations were partially restored by anti-TGF-beta(1) neutralizing antibody.

CONCLUSIONSThese findings suggested that PDGF-BB inhibited p21(WAF1) expression in VSMC partially through upregulating TGF-beta(1) expression via PDGF-BB and TGF-beta signalling pathways.

Animals ; Cell Division ; Cells ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Male ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Platelet-Derived Growth Factor ; pharmacology ; Proto-Oncogene Proteins c-sis ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transforming Growth Factor beta1 ; metabolism

Objective:To explore any effect of on the limb and cardiopulmonary functioning of stroke survivors of combining new Bobath technique with cardiopulmonary rehabilitation.Methods:A total of 160 stroke survivors with limb disorders were randomly divided into an observation group and a control group, each of 80. Both groups were given routine rehabilitation and the new version of Bobath training, but the observation group was additionally provided with 12 weeks of cardiopulmonary rehabilitation. Before and after the treatment the limb functioning of both groups was evaluated along with their ability in the activities of daily living and the recovery of damaged nerve function, using the simplified Fugl-Meyer (FMA) motor function scoring, the modified Barthel index (MBI) and the Chinese stroke scale (CSS). Peak oxygen uptake (VO 2peak), peak metabolic equivalent (METpeak), peak heart rate (HRpeak) and anaerobic thresholds (ATs) were documented. Results:After the treatment the average FMA, MBI and CSS scores and cardiopulmonary indexes had improved significantly in both groups. All were then significantly better in the observation group than in the control group.Conclusions:Combining the new Bobath technique with cardiopulmonary rehabilitation can significantly improve the limb and cardiopulmonary functioning of stroke survivors, as well as their skill in the activities of daily living and the recovery of the damaged nerve functionality. This combination is therefore worthy of clinical promotion and application.

BACKGROUND:Icariin can promote bone formation and inhibit bone resorption,but it is difficult to dissolve in water,and its bioavailability is very low in vivo.Therefore,a suitable carrier is essential to fully utilize the biological activity of icariin.OBJECTIVE:To prepare an icariin/β-tricalcium phosphate (β-TCP) composite scaffold and to characterize its biological characteristics.METHODS:Three-dimensional printing technology was utilized to prepare porous β-TCP scaffolds carrying nano zinc oxide,and the compressive strength of porous β-TCP scaffolds was detected before and after addition of nano zinc oxide.Water absorption and porosity of the porous β-TCP scaffolds were also measured.Ultrasonic emulsification solvent dialysis was performed to prepare icariin/poly(lactic-co-glycolic acid) (PLGA) microspheres,followed by the detection of water absorption and porosity.The porous β-TCP scaffolds and icariin/PLGA microsphere suspension were mixed to prepare icariin/β-TCP composite scaffolds.Microstructure observation of the composite scaffolds was done by scanning electron microscope,and meanwhile,water absorption and porosity were detected.The composite scaffold was then immersed into PBS,and icariin concentration in the supematant was measured at corresponding time points,based on which Icariin cumulative release curve was drawn.RESULTS AND CONCLUSION:(1) The porous microstructure of the porous β-TCP scaffold was regular,well distributed,and the connectivity was good.The pore spacing was about 600 μm.After addition of nano zinc oxide particles,the surface structure of the scaffold was more compact and the crystallinity was higher.(2) PLGA microspheres were spherical with a diameter of 1-4 μm,and the microspheres were uniform in size.(3) The maximum compressive strength of the porous beta tricalcium phosphate scaffold was (2.98±0.78) MPa,and increased to (8.95±0.29) MPa after addition of nano zinc oxide.(4) The water absorption rate and porosity were (25.09±0.96)％ and (66.93±2.84)％ for the porous β-TCP scaffold,(28.46±1.85)％ and (32.65±3.32)％ for the icariin/β-TCP composite scaffold,respectively.(5)The average encapsulation efficiency of the PLGA microspheres was (78.87±2.31)％,and the drug loading was (6.04±1)％.(6) The release amount of icariin could reach 52％ of the total amount at 16 days and 60％ of the total amount at 32 days.These findings indicate that the icariin/β-TCP composite scaffold has good mechanical properties and sustained-release performance.

OBJECTIVE: To evaluate the relationship between postoperative knee function and the sagittal position of tibial component in unicompartmental knee arthroplasty (UKA). METHODS: We retrospectively enrolled the patients who underwent UKA from January 2016 to May 2020. They were assigned into 2 groups according to postoperative posterior tibial slope (PTS): the normal PTS group (PTS≥3° and PTS < 8°) and the abnormal PTS group (PTS < 3° or ≥8°). The patients were followed up for at least 12 months. The postoperative Knee Society Clinical Score (KSS-C), Knee Society Functional Score (KSS-F) and knee range of motion (ROM) were compared between the two groups. RESULTS: A total of 72 patients (82 knees) were included with 51 patients (58 knees) in PTS normal group and 21 patients (24 knees) in PTS abnormal group. All the patients were followed up with median of 23.6 months. There was no significant difference in the general data [gender, age, body mass index (BMI)], pre-operative knee range of motion, preoperative KSS-C score and KSS-F score (P > 0.01). The KSS-C score, KSS-F score, and knee range of motion significantly improved after surgery (P < 0.01) for all the patients. The postoperative KSS-C score in normal PTS group (88.76±2.79) was significantly higher than the KSS-C score in abnormal PTS group (84.42±3.35, P < 0.01), but no significant difference between the 2 groups was observed in postoperative KSS-F score and knee range of motion (P > 0.01). In addition, there was no correlation between the change of PTS and postoperative KSS-C score (r=-0.034, 95%CI: -0.247 to 0.186, P = 0.759), KSS-F score (r = -0.014, 95%CI: -0.238 to 0.198, P = 0.901) and knee range of motion (r= 0.045, 95%CI: -0.214 to 0.302, P = 0.686). CONCLUSION The posterior tibial slope between 3° and < 8° can be recommended to improve knee joint function in mobile UKA, and excessive or insufficient PTS should be avoided.
Arthroplasty, Replacement, Knee ; Humans ; Knee Joint/surgery* ; Knee Prosthesis ; Osteoarthritis, Knee/surgery* ; Range of Motion, Articular ; Retrospective Studies ; Treatment Outcome

Objective: To study the therapeutic effect of Huoxue Tongluo Decoction (HXTLD) on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved. Methods: Network pharmacology was used to predict the key active ingredients and targets of HXTLD. Surgical methods were used to create a rat model of ischemic stroke. The rats were then given a suspension of HXTLD by ig administration. Erectile function was evaluated by Apomorphine (APO) induction. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (Real-time PCR) and Western blotting were used to detect the expression of related mRNAs and proteins in rat penile corpus cavernous tissue and brain tissue. Hematoxylin & Eosin (HE) staining was used to investigate structural changes in the penile cavernous tissue. Results: Network pharmacology showed that tumor necrosis factor (TNF), nitric oxide synthase 3 (eNOS), and vascular endothelial growth factor (VEGF) were the key targets of HXTLD in the treatment of erectile dysfunction caused by ischemic stroke. Experimental studies showed that HXTLD improved erectile dysfunction caused by ischemic stroke. HE results showed that HXTLD improved the structure of the corpus cavernosa. HXTLD also inhibited the expression of TNF and VEGF proteins in penile tissue (P < 0.05) and enhanced the expression of eNOS protein in penile tissue (P < 0.05). Conclusion: HXTLD improved the erectile function of rats with erectile dysfunction caused by ischemic stroke by regulating the mRNA and protein levels of TNF, eNOS and VEGF.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Objective: To estimate the effectiveness of the primary screening strategy for liver cancer in rural areas to provide basic information for the optimization and perfection of the technical program for the early detection and treatment of liver cancer. Methods: Residents including males aged 35-64 and females aged 45-64 from 9 counties in rural China between 2013 and 2015 were selected as the target population. The participant was classified into a high-risk and non-high-risk group based on the standardized questionnaire or HBsAg, and the Chi-squared test was applied to compare differences between the two groups. The Cox proportional hazard regression models were applied to assess hazard ratio (HR) and its 95% confidence interval (CI). Results: 358 348 participants were recruited from 2013 to 2015. 1 196 individuals were identified with liver cancer until December 31, 2021, with an incidence density of 52.0/10(5) person-years. Of the participants, 54 650 were assessed as high risk (15.3%) based on the questionnaire and the status of HBsAg. The high-risk population had a higher incidence density (168.3/10(5) person-years vs 31.5/10(5) person-years) and higher risk of developing liver cancer (HR=2.98, 95% CI=2.64-3.35), compared to the non-high-risk group. Based on the questionnaire-based high-risk assessment system, 47 884 (13.4%) individuals were identified as high risk, who showed statistical differences in terms of incidence density and incidence risk, in comparison to the low-risk population (all P<0.05). HBsAg can screen out a higher proportion of high-risk individuals who are women, non-smokers, non-drinkers, and individuals without a family history of liver cancer (all P<0.05). The sensitivity analysis of the effectiveness of the whole primary screening method is stable, and high-risk individuals still had a higher risk of liver cancer. Conclusions: The primary screening method of the questionnaire-based risk assessment system and HBsAg can achieve satisfactory effectiveness. The questionnaire-based risk assessment system could identify high-risk individuals to some extent, however, it still needs to be improved to meet the actual requirements.
China/epidemiology* ; Early Detection of Cancer ; Female ; Hepatitis B Surface Antigens ; Humans ; Incidence ; Liver Neoplasms/epidemiology* ; Male ; Mass Screening ; Risk Factors