Preparation and <i>in Vitro</i>Drug Release Evaluation of Once-Daily Metformin Hydrochloride Sustained-Release Tablets

The objective of this study was to develop once-daily metformin hydrochloride sustained-release tablets (MHSRT) and evaluate their in vitro release behavior. MHSRT were prepared by the film coating method. The in vitro drug release rate of MHSRT and the commercial tablets Fortamet? made in the United States of America in water was fitted with zero order kinetic equation, and Ritger-Peppas kinetic equation in 0.1 M HCl and pH 6.8-phosphate buffer, respectively. The similarity factor f2 values of MHSRT in three different dissolution medium were 82, 80 and 74, respectively in comparison with imported Fortamet?, which were all greater than 50. The results of storage-stability showed that MHSRT were stable for at least 6 months under stress condition (40℃ ± 2℃, RH 75% ± 5%). Therefore, in this study, MHSRT were successfully prepared using optimized formulation technologies that meet mass produce. The in vitro release behavior of MHSRT was almost similar to that of imported Fortamet?.

Clinical observation of Baitou Weng Decoction combined with mesalazine sustained-release tablets in treating heat-toxic and smoldering ulcerative colitis

Objective:To observe the clinical efficacy of Baitou Weng Decoction combined with mesalazine sustained-release tablets in the treatment of ulcerative colitis with febrile heat and its effect on immune function and serum inflammatory factors.Methods: A total of 84 patients with ulcerative colitis were randomly divided into control group and treatment group, with 42 cases in each group. The control group was given mesalazine sustained-release tablets orally, while the treatment group was given Baitou Weng Decoction and mesalazine sustained-release tablets orally. The treatment period was 30 days and the patients were followed up for 3 months. After treatment, the clinical efficacy, quality of life, immune function and serum inflammatory factors of the two groups were observed.Results: The effective rate of treatment group (90.47%) was higher than that of control group (73.81%) (P<0.05);compared with before treatment, the scores of inflammatory bowel disease quality of life questionnaire scale in both groups were significantly improved (P<0.05), and the difference between the two groups was significant (P<0.05);after treatment, the plasma CD4+/CD8+ ratio and NK+ levels in both groups were significantly higher than those before treatment (P<0.05), and the treatment group was changed. The serum levels of tumor necrosis factor-α, interleukin-17 and interleukin-23 were significantly decreased in both groups after treatment (P<0.05), and the improvement was more significant in the treatment group (P<0.05). No significant adverse reactions were observed in the treatment group.Conclusions: Modified Baitou Weng Decoction combined with mesalazine in the treatment of heat-toxic and incandescent ulcerative colitis can significantly improve the clinical efficacy, improve the quality of life of patients, effectively regulate the expression level of serum inflammatory factors in ulcerative colitis patients, promote the recovery of patients' immune function, and have high drug safety.

Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet,T p; sustained-release capsule,T J and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. T max, C max and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5±16.9 % (T P) and 110.4%±9.6 % (T J). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, T max, C max MRT and DF had significant difference (P<0.05); C av , C min and AUC 0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.

Simultaneous Analysis of Indapamide and Related Impurities in Sustained-Release Tablets by a Single-Run HPLC-PDA Method

The contents of indapamide and related impurities in generic indapamide sustained-release tablets were simultaneously detected by a single-run high performance liquid chromatography equipped with photodiode array detector(HPLC-PDA)method for the quality control in this paper.The results showed the method had a good selectivity and was validated through linearity,limits of detection and quantification,recovery,and precision.The linear ranges of indapamide,2-methyl-1-nitroso-2,3-dihydro-1H-indole(impurity A,ImA),4-chloro-N-(2-methyl-1H-indol-1-yl)-3-sulphamoyl-benzamide(impurity B,ImB)and 4-chloro-3-sulfamoylbenzoic acid(impurity 1,Im1)were 0.028-1.80μg/mL(R=0.99995),0.060-1.20μg/mL(R=0.9996),0.0324-1.20μg/mL(R=0.99985)and 0.060-1.20μg/mL(R=0.9997)with detection limits of 0.0093,0.012,0.012 and 0.006μg/mL,respectively.ImA and Im1 were not detectable in the generic drug.The content of indapamide was 96.7%of the labeled amount with a relative standard deviation(RSD)of 1.30%,and the percentage of ImB relative to the labeled amounts of indapamide was 0.106%with an RSD of 1.82%.The content of other unspecified impurities all met the reference quality standards.The results provided references for the quality control and the quality standard study of generic indapamide sustained-release tablets.

Preparation and evaluation of sustained-release azithromycin tablets in vitro and in vivo

The objective of this study was to prepare azithromycin(AZI)sustained-release products in order to allow for a high dose to be administered,reduce gastrointestinal side-effects and increase the compliance of patients.AZI sustained-release tablets with different release performance(F-I:T_(100%)=3 h and F-II:T_(100%)=8 h in pH 6.0 phosphate buffer)were successfully prepared by wet granulation.The in vitro release rate and drug release mechanism were studied.The release rate of F-Iwas affected by dissolutionmedia with different pH,but not for F-II.HixsoneCrowellmodel was the best regression fitting model for F-I and F-II.Additionally,F-I and F-II both belonged to non-Fick diffusion.Oral pharmacokinetics of the two tablets and one AZI dispersible tablet as reference were studied in six healthy beagle dogs after oral administration.Compared with the reference,the C_(max) of F-I and F-II were decreased,and the T_(max) were prolonged,in that case which meet the requirement of sustained-release tablets.The relative bioavailability of F-I and F-II were 79.12%and 64.09%.T-test ofAUC_(0-144),and AUC_(0-∞) for F-I and F-II indicated there was no significant difference between F-I and F-II.These mean that the extended release rate did not induce different pharmacokinetics in vivo.

Nerve growth factor-basic fibroblast growth factor poly-lactide co-glycolid sustained-release microspheres and the small gap sleeve bridging technique to repair peripheral nerve injury

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.

Tunable and sustained-release characteristics of venlafaxine hydrochloride from chitosan–carbomer matrix tablets based on in situ formed polyelectrolyte complex film coating

The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. Taking venlafaxine hydrochloride(VH) as a drug model, the feasibility of using chitosan(CS), carbomer(CBM) combination system to achieve this goal was studied. Formulation and process variables influencing drug release from CS–CBM matrix tablets were investigated. It was found that CS–CBM combination system weakened the potential influence of CS, CBM material properties and gastric emptying time on drug release profile. Demonstrated by direct observation, differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR), in situ self-assembled polyelectrolyte complex(PEC) film was formed on the tablet surface during gastrointestinal tract transition, which contributed to the tunable and robust control of drug release. The sustained drug release behavior was further demonstrated in vivo in Beagle dogs, with level A in vitro and in vivo correlation(IVIVC) established successfully. In conclusion, CS–CBM matrix tablets are promising system to tune and control the release of highly water-soluble drugs with good system robustness.

Combustion Characteristics of Solid Sustained-Release Energetic Materials

A solid sustained-release energetic material sample,an eruption device and a complete test system were prepared further to analyse the combustion characteristics of solid sustainedrelease energetic materials.The high-temperature heat flux generated by the combustion of the samples from the eruption device was used to penetrate the Q235 target plate.In addition,the meaning and calculation formula of energy density characterising the all-around performance of heat flux were proposed.The numerical simulation of the combustion effect of samples was carried out.According to the data comparison,the numerical simulation results agreed with the experimental results,and the maximum deviation between the two was less than 8.9%.In addition,the structure of the combustion wave and high-temperature jet was proposed and analysed.Based on theoretical analysis,experimental research and numerical simulation,the theoretical burning rate formula of the sample was established.The maximum error between the theoretically calculated mass burning rate and the experimental results was less than 9.8%.Therefore,using the gas-phase steady-state combustion model to study the combustion characteristics of solid sustained-release energetic materials was reasonable.The theoretical burning rate formula also had high accuracy.Therefore,the model could provide scientific and academic guidance for the theoretical research,system design and practical application of solid sustained-release energetic materials in related fields.

The Therapeutic Effect of Biling Weitong Granules Combined with Oryz-Aspergillus Enzyme and Pancreatin Tablet on Reflux Esophagitis with Functional Dyspepsia

Objective:To investigate the therapeutic effect of Biling Weitong Granules combined with oryz-aspergillus enzyme and pancreatin tablets on patients with reflux esophagitis with functional dyspepsia.Methods:Sixty patients diagnosed with reflux esophagitis with functional dyspepsia who were admitted to the Affiliated Hospital of Hebei University between June 2020 and June 2023 were selected and divided into two groups:the control group and the observation group,each consisting of 30 cases.The control group received oryz-aspergillus enzyme and pancreatin tablets only,while the observation group received Biling Weitong Granules in addition to the tablets.The clinical efficacy,Chinese medicine syndrome points,esophageal kinetic indexes,gastrointestinal hormone levels,and therapeutic safety of both groups were evaluated.Results:The total efficiency of the observation group reached 93.33%,significantly higher than the 73.33%of the control group(P<0.05).After treatment,patients in the observation group exhibited significantly lower scores for Chinese medicine symptoms such as early satiety,belching,abdominal distension,abdominal pain,and loss of appetite compared to the control group(P<0.05).Furthermore,the observation group showed significantly higher upper esophageal sphincter pressure,lower esophageal sphincter pressure,and distal esophageal contraction scores compared to the control group(P<0.05).Additionally,levels of gastric motility hormone,vasoactive intestinal peptide,and gastrin were significantly higher in the observation group compared to the control group(P<0.05).Throughout the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,indicating comparable safety of the two treatment modalities(P>0.05).Conclusion:The combination of Biling Weitong Granules with oryz-aspergillus enzyme and pancreatin tablets demonstrates significant efficacy in the treatment of reflux esophagitis with functional dyspepsia,with a better safety profile.This finding warrants further clinical promotion.

The preparation and the in-vitro pharmacodynamics study of the intracapsular sustained-release preparations for the prevention of posterior capsule opacification

Docetaxel-loaded sustained-release preparation based on 2-Hydroxyethyl methacrylate(HEMA)and Methyl methacrylate(MMA)cross-linked copolymer(P(HEMA-co-MMA))was prepared to examine the potential use for preventing posterior capsule opacification(PCO).The preparations were prepared by polymerizing the mixture of HEMA,MMA,cross-linking agent(EGDMA),initiator(AIBN)and docetaxel.The influence factors and mechanism of drug release were studied in the experiments.FT-IR,X-RD and SEM methods were used to characterize the polymer(P(HEMA-co-MMA))and docetaxel-loaded sustained-release preparations.Biocompatibility of P(HEMA-co-MMA)and in-vitro effect of docetaxel-loaded sustained-release preparations were also evaluated.The results showed that docetaxel could release sustainedly from these preparations prepared by cross-linking polymerization.And the release rate could be accelerated by increasing the MMA ratio or EGDMA ratio of the polymer.Release mechanism of docetaxel fitted the Higuchi model well.The results of IR and X-RD showed that only a hydrogen bond was formed between docetaxel and P(HEMA-co-MMA).Docetaxel dispersed in P(HEMA-co-MMA)in amorphous form.The elution test showed that P(HEMA-co-MMA)had good biocompatibility and the in-vitro pharmacodynamics study proved that docetaxel could release stably from the preparations and inhibit HLECs’proliferation.The docetaxel-loaded sustained-release preparations proved to be a promising therapy for preventing PCO.These results also lay a theoretical and experimental foundation for the future.

Preparation and evaluation of tamsulosin hydrochloride sustained-release pellets modified by two-layered membrane techniques

The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques.Centrifugal granulator and fluidizedbed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively.The prepared pellets were evaluated for physicochemical characterization,subjected to differential scanning calorimetry(DSC)and in vitro release of different pH.Different release models and scanning electron microscopy(SEM)were utilized to analyze the release mechanism of Harnual■ and home-made pellets.By comparing the dissolution profiles,the ratio and coating weight gain of Eudragit■ NE30D and Eudragit■ L30D55 which constitute the inside membrane were identified as 18:1 and 10%-11%.The coating amount of outside membrane containing Eudragit■ L30D55 was determined to be 0.8%.The similarity factors(f_(2))of home-made capsule and commercially available product(Harnual■)were above 50 in different dissolution media.DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual■ and self-made pellets before and after dissolution.According to Ritger-Peppas model,the two dosage form had different release mechanism.

No long-term survival benefit with sustained-release 5-fluorouracil implants in patients with stages Ⅱ and Ⅲ gastric cancer

BACKGROUND The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil(5-FU) in advanced-stage gastric cancer is still unelucidated.AIM To explore the long-term survival benefit of using sustained-release 5-FU implants in stage Ⅱ and stage Ⅲ gastric cancer patients.METHODS Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release(SR) chemotherapy with 5-FU was used or not(NSR). The primary end-point was 5-year overall survival. Kaplan–Meier method with logrank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients.RESULTS In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219(70.9%) were men, with an average age of 58.25 years. Furthermore, 56(18.1%) received neoadjuvant chemotherapy, and 191(61.8%) were in TNM stage Ⅲ. In addition, 158 patients received intraoperative sustainedrelease chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate(P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival.CONCLUSION Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.

Evaluation of Control Effects against Sugarcane Pests：A New Sustained-release and Long-lasting Pesticide and Convenient and Efficient Pesticide Application Technology

[Objective]The paper was to screen a new ideal sustained-release,long-lasting and low-toxic pesticide and convenient and efficient pesticide application technology for controlling Ceratovacuna lanigera and Baliathrips serratus. [Method]2% Imidacloprid GR were selected and applied in the soil for field efficacy trial. [Result] The optimum dosage of 2% imidacloprid GR was 30 kg/hm^2( active ingredient 600 g),which can be mixed with fertilizer( 30 kg pesticide and 40-80 kg fertilizer per hm^2) once combined with sugarcane planting management or big ridging during February and June. The control effects against C. lanigera and B. serratus could be more than 98. 2% and 81. 1%,respectively. The actual yield and sugar content in various pesticide treatments were increased by 33 390 kg/hm^2 and 6. 6% respectively compared to blank control. [Conclusion]2% imidacloprid GR has good control effects on C. lanigera and B. serratus. It is a new pesticide with ideal sustained-release,long-lasting and low-toxin effects against C. lanigera and B. serratus. Therefore,it could be used alternatively with other pesticides,to delay production and development of drug resistance.

PDLLA/β-TCP/HA/CHS/NGF Sustained-release Conduits for Peripheral Nerve Regeneration

Using nerve guide conduits (NGCs) to promote the regeneration of PNI is a feasible alternative to autograft.Compared with NGCs made of single material,composite NGCs have a greater development prospect.Our previous research has confirmed that poly(D,L-lactic acid)/β-tricalcium phosphate/hyaluronic acid/chitosan/nerve growth factor (PDLLA/β-TCP/HA/CHS/NGF) NGCs have excellent physical and chemical properties,which can slowly release NGF and support cell adhesion and proliferation.In this study,PDLLA/β-TCP/HA/CHS/NGF NGCs were prepared and used to bridge a 10 mm sciatic nerve defect in 200-250 g Sprague-Dawley (SD) rat to verify the performance of the NGCs in vivo.Substantial improvements in nerve regeneration were observed after using the PDLLA/β-TCP/HA/CHS/NGF NGCs based on gross post-operation observation,triceps wet weight analysis and nerve histological assessment.In vivo studies illustrate that the PDLLA/β-TCP/HA/CHS/NGF sustained-release NGCs can effectively promote peripheral nerve regeneration,and the effect is similar to that of autograft.

In vitro release of 1,3-bis(2-chloroethyl)-1-nitrosourea sustained-release microspheres and the distribution in rat brain tissues

BACKGROUND: The implantation of released chemotherapeutic drugs, which takes biodegradable polymer as vector, into the tumor site can get high concentration and release the drug for a long time, it can directly act on the tumor cells, and reduce the general toxicity. OBJECTIVE: To explore the in vitro and in vivo course of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) sustained-release from BCNU-loaded polylactide (PLA) microspheres (MS) and location in rat brain tissue. DESIGN: A repetitive measurement. SETTING:Central Pharmacy, General Hospital of Chinese People's Armed Police Forces. MATERIALS: Thirty male SD rats were used. PLA (Mr5000, batch number: KSL8377) was produced by Wako Pure Chemical Inc.,Ltd. (Japan); BCNU (batch number: 021121) by Tianjin Jinyao Amino Acid Co., Ltd.; BCNU-PLA-MS was prepared by the method of solvent evaporation and pressed into tablets (10 mg/tablet). High-performance liquid chromatography (HPLC) Agilent 1100 (USA); LS9800 liquid-scintillation radiometric apparatus (Beckman). Chromatographic conditions: Elite Hypersil ODS2 C18 chromatographic column (5 μm, 4.6 mm×150 mm); Mobile phase: methanol: water (50:50), flow rate was 1.0 mL per minute, wave length of ultraviolet detection was 237 nm, and the inlet amount of samples was 10 μL. METHODS: The experiments were carried out in the experimental animal center of the General Hospital of Chinese Armed Police from May 2004 to July 2005. ① In vitro BCNU-PLA-MS release test: BCNU-PLA-MS was prepared by the method of solvent evaporation, then placed in 0.1 mol/L phosphate buffered solution (PBS, pH 7.4, 37 ℃), part of MS were taken out at 1, 2, 3, 7, 10 and 15 days respectively, and the rest amount of BCNU in MS was determined by HPLC, then the curve of BCNU-PLA-MS release was drawn. ②In vivo BCNU-PLA-MS release and distribution test: The rats were anesthetized, then BCNU-PLA-MS were implanted to the site 1 mm inferior to the cortex of frontal lobe. Five rats were killed postoperatively at 4 hours, 1, 2, 3, 7 and 15 days, the residual MS was removed from the brain tissue. The rest amount of BCNU was determined with HLPC, and the curve of BCNU-PLA-MS release was drawn as compared with the amount of BCNU in the implanted tablets. Besides, brain tissues (1 g) at the implanted side and the contralateral one were obtained respectively, blood sample (0.5 mL) was also collected, 3H-BCNU was counted radioactively in radioactive liquid flash solution. The distributions of BCNU-PLA-MS in normal rat brain tissue and serum were detected. The analysis of variance was applied to compare the intergroup differences of the measurement data. MAIN OUTCOME MEASURES: ① Characteristics of BCNU-PLA-MS release in phosphate buffered solution (PBS) and rat brain tissue; ② Distributions of BCNU-PLA-MS in normal rat brain tissue and serum. RESULTS: ① Release of BCNU-PLA-MS in PBS and rat brain tissue: The BCNU released from BCNU-PLA-MS could be sustained for over 2 weeks both in PBS and brain tissue. In PBS, the released rate of BCNU was over 15% at 24 hours, nearly 50% at 72 hours and over 90% at 15 days. In brain tissue, the released rate was 8% at 4 hours, 16% at 24 hours, 60% at 72 hours, respectively, and BCNU could be sustained released for over 15 days. ② Distributions of BCNU-PLA-MS in normal rat brain tissue and serum: The concentrations of BCNU in the ipsilateral brain tissue were 6 to 70 times higher than those in the contralateral one. The concentrations of BCNU in the ipsilateral brain tissue were obviously higher than those in serum and contralateral brain tissue (F =103.47, P < 0.01). CONCLUSION: BCNU-PLA-MS can increase the drug concentration in targeted brain tissue, decrease that in the non-targeted brain tissue, reduce general toxic and side effects, and have good releasing function.

Toxic response of aquatic organisms to guide application of artemisinin sustained-release granule algaecide

In our previous study,we prepared the granules by embedding artemisinin into alginate-chitosan using microcapsule technology.These granules can release artemisinin sustainably and have a strong inhibitory effect on the growth of both single Microcystis aeruginosa and mixed algae.To safely and effectively use artemisinin sustained-release granules to control algal blooms,the ecotoxicity was studied by assessing their acute and chronic toxicity to Daphnia magna(D.magna)and Danio rerio(D.rerio),along with their antioxidant activities.The results showed that the 48-h median effective concentration(EC50)of pure artemisinin to D.magna was 24.54 mg/L and the 96-h median lethal concentration(LC50)of pure artemisinin to D.rerio was 68.08 mg/L.Both values were classified as intermediate toxicity according to the Organization for Economic Co-operation and Development(OECD).The optimal algae inhibitory concentration of artemisinin sustained-release granules(1 g/L)had low acute toxicity to both D.magna and D.rerio.The sustained-release granules had higher chronic toxicity to D.magna than to D.rerio.Partial indices of D.magna were inhibited by granules when the concentrations were larger than 0.1 g/L.Low granule concentration had an inductive effect on antioxidant enzyme activities in D.magna and D.rerio.With the increase of the exposure concentration and time,the enzyme activity presented a trend of first increasing and then decreasing,and the overall changes were significant.The change trend and range of enzyme activity indicated that the granules could cause serious oxidative stress to D.magna and D.rerio,and the changes were consistent with the results of toxicity experimentation.

Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

Investigation of Tablet Defects by AI Based Terahertz Technology

Recently a lot of medical tablets with special packets in the global market are available. For the safety and purity of the tablet, we need to scan it by developed scanner technology, which should be not more expensive and easily available in the market. The THz technology is one of them. In the proposed work, we have tasted tablet images with the help of the THz super-resolution scanner, which is already available in our lab. The AI machine learning data concept has been investigated. Good resolution of images has been obtained. Furthermore, the challenging research problems are discussed. Finally, it summarizes the recent updates in terahertz technology for drug inspection and medical applications with potential research challenges.