“LIVING”/CONTROLLED RADICAL POLYMERIZATION OF ETHYL METHYLACRYLATE WITH 2,2’-AZOBISISOBUTYRONITRILE/FERRIC CHLORIDE/TRIPHENYLPHOSPHINE INITIATION SYSTEM

'Living'/controlled radical polymerization of ethyl methacrylate (EMA) was carried out with a 2,2'-azobisisobutyronitrile (AIBN)/ferric chloride (FeCl_3)/triphenylphosphine (PPh_3) initiation system at 85℃. Thc numberaverage molecular weight (M_n) increases linearly with monomer conversion and the rate of polymerization is first order withrespect to monomer concentration. The M_w of PEMA ranges from 3900 to 17600 and the polydispersity indices are quitenarrow (1.09～1.22). The conversion can reach up to～100% and M_w of the polymers obtained is close to that designed. Thepolymerization mechanism belongs to the reverse atom transfer radical polymerization (ATRP). The polymer was end-functionalized by chlorine atom, which acts as a macroinitiator to proceed extension polymerization in the presence ofCuBr/bipy catalyst system via an ATRP process. The presence of ω-chlorine in the PEMA obtained was identified by ~1H-NMR spectrum.

Association of the glycemic background patterns and the diabetes management efficacy in poorly controlled type 2 diabetes

BACKGROUND Inadequate glycemic control in patients with type 2 diabetes(T2DM)is a major public health problem and a significant risk factor for the progression of diabetic complications.AIM To evaluate the effects of intensive and supportive glycemic management strategies over a 12-month period in individuals with T2DM with glycated hemoglobin(HbA1c)≥10%and varying backgrounds of glycemic control.METHODS This prospective observational study investigated glycemic control in patients with poorly controlled T2DM over 12 months.Participants were categorized into four groups based on prior glycemic history:Newly diagnosed,previously well controlled with recent worsening,previously off-target but now worsening,and HbA1c consistently above 10%.HbA1c levels were monitored quarterly,and patients received medical,educational,and dietary support as needed.The analysis focused on the success rates of good glycemic control and the associated factors within each group.RESULTS The study showed significant improvements in HbA1c levels in all participants.The most significant improvement was observed in individuals newly diagnosed with diabetes:65%achieved an HbA1c target of≤7%.The results varied between participants with different glycemic control histories,followed by decreasing success rates:39%in participants with previously good glycemic control,21%in participants whose glycemic control had deteriorated compared to before,and only 10%in participants with persistently poor control,with mean HbA1c levels of 6.3%,7.7%,8.2%,and 9.7%,respectively.After one year,65.2%of the“newly diagnosed patients”,39.3%in the“previously controlled group”,21.9%in the“previously off-target but now worsened'”group and 10%in the“poorly controlled from the start”group had achieved HbA1c levels of 7 and below.CONCLUSION In poorly controlled diabetes,the rate at which treatment goals are achieved is associated with the glycemic background characteristics,emphasizing the need for tailored strategies.Therefore,different and comprehensive treatment approaches are needed for patients with persistent uncontrolled diabetes.

Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

BACKGROUND Mesenchymal stem cells(MSCs)as living biopharmaceuticals with unique properties,i.e.,stemness,viability,phenotypes,paracrine activity,etc.,need to be administered such that they reach the target site,maintaining these properties unchanged and are retained at the injury site to participate in the repair process.Route of delivery(RoD)remains one of the critical determinants of safety and efficacy.This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure(HF)based on phase II randomized clinical trials(RCTs).We hypothesize that the RoD modulates the safety and efficacy of MSCbased therapy and determines the outcome of the intervention.AIM To investigate the effect of RoD of MSCs on safety and efficacy in HF patients.METHODS RCTs were retrieved from six databases.Safety endpoints included mortality and serious adverse events(SAEs),while efficacy outcomes encompassed changes in left ventricular ejection fraction(LVEF),6-minute walk distance(6MWD),and pro-B-type natriuretic peptide(pro-BNP).Subgroup analyses on RoD were performed for all study endpoints.RESULTS Twelve RCTs were included.Overall,MSC therapy demonstrated a significant decrease in mortality[relative risk(RR):0.55,95%confidence interval(95%CI):0.33-0.92,P=0.02]compared to control,while SAE outcomes showed no significant difference(RR:0.84,95%CI:0.66-1.05,P=0.11).RoD subgroup analysis revealed a significant difference in SAE among the transendocardial(TESI)injection subgroup(RR=0.71,95%CI:0.54-0.95,P=0.04).The pooled weighted mean difference(WMD)demonstrated an overall significant improvement of LVEF by 2.44%(WMD:2.44%,95%CI:0.80-4.29,P value≤0.001),with only intracoronary(IC)subgroup showing significant improvement(WMD:7.26%,95%CI:5.61-8.92,P≤0.001).Furthermore,the IC delivery route significantly improved 6MWD by 115 m(WMD=114.99 m,95%CI:91.48-138.50),respectively.In biochemical efficacy outcomes,only the IC subgroup showed a significant reduction in pro-BNP by-860.64 pg/mL(WMD:-860.64 pg/Ml,95%CI:-944.02 to-777.26,P=0.001).CONCLUSION Our study concluded that all delivery methods of MSC-based therapy are safe.Despite the overall benefits in efficacy,the TESI and IC routes provided better outcomes than other methods.Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.

Transient elastography(Fibro Scan~?) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease- Where do we stand?

Non-alcoholic fatty liver disease(NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of steatosis and fibrosis(laboratory tests and ultrasonography) or cannot be applied as a screening procedure(liver biopsy). Among the non-invasive tests, transient elastography(Fibro Scan?, TE) with controlled attenuation parameter(CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs.

Controlled attenuation parameter for evaluating liver steatosis in chronic viral hepatitis

AIM: To assess the performance of controlled attenuation parameter (CAP) in patients with chronic viral hepatitis.

A Concise Review of Gold Nanoparticles-Based Photo-Responsive Liposomes for Controlled Drug Delivery

The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosystem, liposomes naturally come under the spotlight of this trend. This review summarizes the latest development about the design and construction of photo-responsive liposomes with gold nanoparticles for the controlled drug release. Alongside, we overview the mechanism involved in this process and the representative applications.

Controlled delivery of ibuprofen from poly(vinyl alcohol)-poly(ethylene glycol) interpenetrating polymeric network hydrogels

Hydrogels composed of poly(vinyl alcohol)(PVA) and poly(ethylene glycol)(PEG) were synthesized using glutaraldehyde as crosslinker and investigated for controlled delivery of the common anti-inflammatory drug, ibuprofen(IBF). To regulate the drug delivery, solid inclusion complexes(ICs) of IBF in β–cyclodextrin(β–CD) were prepared and added to the hydrogels. The ICs were prepared by the microwave irradiation method, which is more environmentally benign. The formation of IC was confirmed by various analytical techniques and the synthesized hydrogels were also characterized. Controlled release of drug was achieved from the hydrogels containing the ICs in comparison to the rapid release from hydrogels containing free IBF.The preliminary kinetic analysis emphasized the crucial role of β–CD in the drug release process that influences the polymer relaxation, thereby leading to prolonged release. The cytotoxicity assay validated the hydrogels as non-toxic in nature and hence can be utilized for controlled delivery of IBF.

Effect of post-stroke sensory disorders on the recovery processes of motor function and activity of daily living A non-randomized synchronical controlled trial

BACKGROUND： In the rehabilitation of stroke patients, clinicians usually concentrate on motor problems, such as spasm of limbs and restriction of joint motion, while sensory and perceptive problems are almost always neglected, although they are just as important. One such area is the sensory disorder. OBJECTIVE： To evaluate the motor function and activities of daily living in stroke patients with and without sensory disorders after treatment of integrated western and Chinese medicine. DESIGN： A non-randomized synchronically controlled trial. SETTING： First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine. PARTICIPANTS： Totally 500 stroke inpatients were selected from the Department of Acupuncture and Massage, the First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine from January 2003 to December 2004. They all had suffered from stroke in the last 4 weeks and accompanied by sensory disorder of the ipsilateral limb to different severity. The patients were all accorded with the Diagnostic and Efficacy Evaluative Standards for Stroke （in trial） set by the Encephalopathy Emergency Assistant Group, the State Administration of Traditional Chinese Medicine in 1995, and they were diagnosed by imaging examination. The patients were stratified into sensory disorder group （n =220） and normal sense group （n =280）. Informed consent for the detected items and therapeutic program was obtained from the relatives of all the participants. The study was approved by the hospital ethical committee. METHODS： All the patients were treated with acupuncture of Xing Nao Kai Qiao for restoring consciousness and inducing resuscitation, assisted by traditional Chinese medicine and western medicine specific to corresponding symptoms. The therapeutic principles were restoring consciousness and inducing resuscitation, nourishing liver and kidney, and dredging meridian. In addition, the patients were given western medical treatments for decreasing intracranial pressure, thrombolysis, reducing blood viscosity, anticoagulation, anti-arteriosclerosis, ameliorating microcirculation, also administrated with activator for nerve cells. MAIN OUTCOME MEASURES： （1） The severity of motor function deficit was evaluated using clinical neurological deficit score for stroke patients set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995; （2） The activities of daily living was evaluated with Barthel Index, the higher the score, the better the independence, and the less the dependence. RESULTS： All the 500 stroke patients were involved in the final analysis of results. （1） The neurological deficit scores before treatment had no significant difference between the two groups （P 〉 0.05）, but the scores after treatment were significantly decreased as compared with those before treatment in both groups （t =6.59, 12.43, P 〈 0.01）. The neurological deficit score after treatment in the normal sense group was significantly lower than that in the sensory disorder group （t =1.63, P 〈 0.05）. （2） The scores of activities of daily living after treatment were significantly increased as compared with those before treatment in both groups （t =16.03, 25.10, P 〈 0.01）. The scores of activities of daily living in the normal sense group were higher than those in the sensory disorder group both before and after treatment （t =6.07, 14.26, P 〈 0.05）. CONCLUSION： Sensory disorders have obvious negative effects on the recovery of motor function and activities of daily living of stroke patients.

Versatile and controlled quantum teleportation network

A quantum teleportation network involving multiple users is essential for future quantum internet.So far,controlled quantum teleportation has been demonstrated in a three-user network.However,versatile and controlled quantum teleportation network involving more users is in demand,which satisfies different combinations of users for practical requirements.Here we propose a highly versatile and controlled teleportation network that can switch among various combinations of different users.We use a single continuous-variable six-partite Greenberger-Horne-Zeilinger(GHZ)state to realize such a task by choosing the different measurement and feedback operations.The controlled teleportation network,which includes one sub-network,two sub-networks and three sub-networks,can be realized for different application of user combinations.Furthermore,the coherent feedback control(CFC)can manipulate and improve the teleportation performance.Our approach is flexible and scalable,and would provide a versatile platform for demonstrations of complex quantum communication and quantum computing protocols.

Diagnostic value of controlled attenuation parameter for liver steatosis in patients with chronic hepatitis B

AIM: To study the diagnostic value of controlled attenuation parameter (CAP), evaluated by transient elastography, for liver steatosis in patients with chronic hepatitis B (CHB).

Structure-Property Relationships and Models of Controlled Drug Delivery of Biodegradable Poly (D, L-lactic acid) Microspheres

An oil-in-water (O/W) solvent evaporation method was used to prepare biodegradable microspheresbased on poly(D,L-lactic acid) (PLA). Nifedipine, a hydrophobic drug, was chosen as a model molecule in the studyof drug entrapment and release. Effect of preparation conditions on the size, morphology, drug loading, and releaseprofiles of micropheres was investigated. Based on in vitro release experimental findings, a diffusion/dissolutionmodel was presented for quantitative description of the resulting release behaviors and drug release kinetics fromPLA microspheres analyzed. The mathematical models were used to predict the effect of microstructure on theresulting drug release. It provided an approach to determine the suitable structure parameters for microspheres toachieve desired drug release behaviors.

Controlled/"Living"?Radical Polymerization of (-)-Menthyl Methacrylate

The atom transfer radical polymerization(ATRP) of (-)-menthyl methacrylate((-)-MnMA) mediated by CuCl/bipyridine and ethyl 2-bromopropionate or 1-phenylethyl bromide in THF system has been studied. The dependence of the specific rotation on molecular weight and the CD of Poly((-)-MnMA) thus obtained was investigated.

Nitroxide-Mediated Photo-Controlled/Living Radical Polymerization of Methacrylic Acid

The photo-controlled/living radical polymerization of methacrylic acid (MAA) was performed at room temperature by irradiation with a high-pressure mercury lamp using azo initiators and 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl as the mediator in the presence of (4-tert-butylphenyl)diphenylsulfonium triflate (tBuS) as the accelerator. Whereas the bulk polymerization yielded polymers with a bimodal molecular weight distribution in both the absence and presence of tBuS, the solution polymerization in methanol produced unimodal polymers with the molecular weight distribution of 2.0 - 2.3 in the presence of tBuS. The molecular weight distribution of the resulting poly (MAA) decreased with an in- crease in tBuS. The dilution of the monomer concentration also reduced the molecular weight distribution. The use of the initiator with a low 10-h half-life temperature also effectively controlled the molecular weight. The livingness of the polymerization was confirmed by obtaining linear increases in the first-order conversion versus time, the molecular weight versus the conversion, and the molecular weight versus the reciprocal of the initiator concentration.

BIODEGRADABLE POLYMERS WITH A PHOSPHORYL-CONTAINING BACKBONE:TISSUE ENGINEERING AND CONTROLLED DRUG DELIVERY APPLICATIONS

This review provides a glimpse of the potential of the biodegradable phos-phoryl-containing polymers in medical applications. Undoubtedly these polymerspossess unique properties that are yet to be fully understood. Many areas warrantfurther investigation and much optimization remains to be done. The fascinatingchemistry of phosphorus poses interesting hurdles but at the same time leavesample room for polymer scientists to exercise their creativity in designinginteresting biomaterials. As the mutual understanding between basic and clinicalscientists on the need of medical devices and the capabilities of these newbiomaterials expands, imaginative application of new biomaterials to other medi-cal applications can be expected.

pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment

In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.

New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase Ⅱ trial

AIM To evaluate the efficacy and safety of HL tablet extracted from magnolia officinalis for treating patients with nonalcoholic fatty liver disease(NAFLD).METHODS Seventy-four patients with NAFLD diagnosed by ultrasonography were randomly assigned to 3 groups given high dose(400 mg) HL tablet, low dose(133.4 mg) HL tablet and placebo, respectively, daily for 12 wk. The primary endpoint was post-treatment change of hepatic fat content(HFC) measured by magnetic resonance spectroscopy. Secondary endpoints included changes of serum aspartate aminotransferase, alanine aminotransferase(ALT), cholesterol, triglyceride, free fatty acid, homeostasis model assessment-estimated insulin resistance, and body mass index(BMI).RESULTS The mean HFC of the high dose HL group, but not of the low dose group, declined significantly after 12 wk of treatment(high dose vs placebo, P = 0.033; low dose vs placebo, P = 0.386). The mean changes of HFC from baseline at week 12 were-1.7% ± 3.1% in the high dose group(P = 0.018),-1.21% ± 4.97% in the low dose group(P = 0.254) and 0.61% ± 3.87% in the placebo group(relative changes compared to baseline, high dose were:-12.1% ± 23.5%, low dose:-3.2% ± 32.0%, and placebo: 7.6% ± 44.0%). Serum ALT levels also tended to decrease in the groups receiving HL tablet while other factors were unaffected. There were no moderate or severe treatment-related safety issues during the study.CONCLUSION HL tablet is effective in reducing HFC without any negative lipid profiles, BMI changes and adverse effects.

How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB do not guarantee reporting completeness.

Efficacy of a Nutritional Cream Intervention to Treat Depression in Rescuers:A Randomized Controlled Trial

Objective To explore the effectiveness of a nutritional intervention in rescuers who screened positive for depression.Methods A randomized controlled trial design was employed.From June to August,2022,4,460 rescuers were screened using the Self-Rating Depression Scale(SDS),and 1,615 positive cases were identified.Thirty-one volunteers were recruited and randomly divided into a nutritional intervention group and a control group.The intervention group received health education and nutritional intervention(a compound paste therapy primarily composed of red roses and Seville orange flowers),while the control group received psychological education.SDS scores were assessed before and after the intervention.Results There was a statistically significant decline in SDS scores in the nutritional intervention group after the intervention(P<0.05).Furthermore,the SDS scores of the intervention group were significantly lower than those of the control group,both before and after the intervention(P<0.05).No severe adverse reactions were observed during safety evaluation.Conclusion The nutritional intervention effectively reduced the depression scores in rescuers.Early nutritional intervention is recommended for rescuers who initially screen positive for depression.

Real-time model correction using Kalman filter for Raman-controlled cell culture processes

Raman spectroscopy has found extensive use in monitoring and controlling cell culture processes.In this context,the prediction accuracy of Raman-based models is of paramount importance.However,models established with data from manually fed-batch cultures often exhibit poor performance in Raman-controlled cultures.Thus,there is a need for effective methods to rectify these models.The objective of this paper is to investigate the efficacy of Kalman filter(KF)algorithm in correcting Raman-based models during cell culture.Initially,partial least squares(PLS)models for different components were constructed using data from manually fed-batch cultures,and the predictive performance of these models was compared.Subsequently,various correction methods including the PLS-KF-KF method proposed in this study were employed to refine the PLS models.Finally,a case study involving the auto-control of glucose concentration demonstrated the application of optimal model correction method.The results indicated that the original PLS models exhibited differential performance between manually fed-batch cultures and Raman-controlled cultures.For glucose,the root mean square error of prediction(RMSEP)of manually fed-batch culture and Raman-controlled culture was 0.23 and 0.40 g·L^(-1).With the implementation of model correction methods,there was a significant improvement in model performance within Raman-controlled cultures.The RMSEP for glucose from updating-PLS,KF-PLS,and PLS-KF-KF was 0.38,0.36 and 0.17 g·L^(-1),respectively.Notably,the proposed PLS-KF-KF model correction method was found to be more effective and stable,playing a vital role in the automated nutrient feeding of cell cultures.

Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.