This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

Objective To analyze the risk factors for gait disorder in patients with developmental dysplasia of the hip(DDH)after total hip replacement.Methods Sixty DDH patients who underwent total hip replacement at The Second People's Hospital of Kunshan from August 2018 to August 2023 were selected as research objects.Of them,19 patients with gait disorders were assigned to observation group,and 41 without gait disorders were taken as control group.Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for gait disorders in DDH patients after total hip replacement.Results There was no significant difference in the gender,age,disease duration,place of residence,educational level,American Society of Anesthesiologists(ASA)grade,surgical time,intraoperative blood loss,Tonnis classification,or symmetrical skin lines on lower limbs between the two groups(P>0.05).But there were significant differences in terms of equal length of lower limbs,anterior pelvic tilt,cerebral small vessel disease,Parkinson disease,and peripheral nerve injury in lower limbs between the two groups(P<0.05).Equal length of lower limbs,anterior pelvic tilt,cerebral small vessel disease,Parkinson disease,and peripheral nerve injury in lower limbs were risk factors for gait disorders in DDH patients after total hip replacement(P<0.05).Conclusion The occurrence of gait disorders is related to the equal length of lower limbs,anterior pelvic tilt,cerebral small vessel disease,Parkinson disease,and peripheral nerve injury in lower limbs in DDH patients after total hip replacement.Symptomatic treatment should be given timely so as to prevent gait disorders and improve the prognosis.

Objective To study the application of mesoporous silica nanoparticle(MSN)as drug carriers in the treatment of osteoarthritis(OA).Methods Core-cone structured MSN(MSN-CC)was synthesized by sol-gel method,modified by polyethyleneimine(PEI),and loaded with hyaluronic acid synthase 2(HAS2).Forty OA model rats were randomly assigned to OA group,MSN-CC-PEI group,hyaluronic acid(HA)group,or MSN-CC-PEI-HAS2 group.Ten healthy rats were assigned to control group.Normal saline 100 μL was injected into the knee joint in the control group and OA group.MSN-CC-PEI 100 μL,HA solution 100 μL,and MSN-CC-PEI-HAS2 100 μL were injected in MSN-CC-PEI group,HA group,and MSN-CC-PEI-HAS2 group,respectively.The levels of HA,interleukin-1β(IL-1β),and prostaglandin E2(PGE2)in the joint effusion and the foot swelling degree were measured at 1,2,and 3 weeks after injection.Results HA level in the MSN-CC-PEI-HAS2 group was significantly lower than that in the HA group at 1 week after intervention(P<0.05),while HA level in the MSN-CC-PEI-HAS2 group was significantly higher than that in the HA group at 2 and 3 weeks after intervention(P<0.05).With the time going on,HA level in the HA group was gradually decreased(P<0.05),but HA level in the MSN-CC-PEI-HAS2 group was gradually increased(P<0.05).At 1 and 2 weeks after intervention,compared with the HA group,IL-1β,PGE2 and foot swelling degree in the MSN-CC-PEI-HAS2 group were increased(P<0.05).At 3 weeks after intervention,compared with the HA group,IL-1β,PGE2 and foot swelling degree in the MSN-CC-PEI-HAS2 group were decreased(P<0.05).With the time going on,IL-1β,PGE2 and foot swelling degree in the HA group and MSN-CC-PEI-HAS2 group were gradually decreased(P<0.05).Conclusion MSN carrier can stably stimulate the secretion of endogenous HA,reduce the inflammatory response within joint cavity of OA rats,and improve the joint morphology and soft tissue pathological changes.

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

Objective To investigate the dosimetric effects of different calculation grid size(CGS)in helical tomotherapy(HT)planning system on stereotactic body radiation therapy(SBRT)for non-small cell lung cancer(NSCLC).Methods Nine NSCLC patients receiving radiation therapy for the first time at some hospital from March 2019 to December 2022 were selected as the subjects.SBRT planning was carried out through the HT system with three different CGS plans(Fine,Normal,and Coarse)and the same pitch,modulation factor(MF)and optimization conditions,and the target area indexes of the three CGS plans were compared including conformity index(CI),homogeneity index(HI),dosimetric parameters of the organ at risk(OAR),point dose verification pass rate,treatment time,number of monitor units and Sinograms.SPSS 22.0 was used for statistical analysis.Results For target area HI,there weres significant differences between CGS Fine plan and Coarse plan and between CGS Normal plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan(P＞0.05).For target area CI,there were significant differences between CGS Fine plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan and between CGS Normal plan and Coarse plan(P＞0.05).For OAR dosimetric parameters,CGS Fine plan and Coarse plan had significant differences in heart Dmax and Dmean,esophageal Dmax and Dmean,V5,V20,V30 and Dmean of the whole lung and affected lung,V5 and Dmax of the affected lung and heart V10 and V30(P＜0.05),CGS Normal plan and Coarse plan had obvious differences in esophageal Dmax(P＜0.05),and the remained dosimetric parameters were not statistically significant(P＞0.05).Fine,Normal and Coarse plans had the point dose verifica-tion pass rates being 0.96％,1.50％and 1.77％,respectively.In terms of treatment time and number of monitor units,there were significant differences between Fine plan and Coarse plan(P＜0.05)while no statistical differences were found between Fine and Normal plans and between Normal and Coarse plans(P＞0.05).Sinograms analyses showed Fine plan had evenly distributed segment color gradient,Coarse plan had areas of very dark and very light color gradients and Normal plan was somewhere in between.Conclusion Low CGS has to be used as much as possible to obtain accurate dose distribution during SBRT planning for NSCLC patients,which contributes to the execution of the radiation therapy plan and the prevention of ad-verse effects.[Chinese Medical Equipment Journal,2024,45(2):52-57]

Objective To observe the clinical efficacy of ultra-micro acupotomology combined with high and low frequency repetitive transcranial magnetic stimulation(rTMS)in the treatment of upper limb spasm after stroke.Methods A total of 106 patients with upper limb spasm after stroke were randomly divided into observation group and control group,53 cases in each group.Both groups were treated with conventional drugs and exercise therapy.The control group was treated with high and low frequency rTMS.The observation group was treated with ultra-micro needle knife on the basis of the control group.Both groups were treated for four weeks.After two weeks and four weeks of treatment,the clinical efficacy of the two groups was evaluated respectively.The changes of modified Ashworth scale(MAS)score and upper limb Fugl-Meyer scale score were observed before and after treatment in the two groups.The changes of Berg Balance Scale(BBS)score and modified Barthel Index(BI)score were compared before and after treatment between the two groups.The safety and adverse reactions of the two groups were evaluated.Results(1)After two weeks of treatment,the total effective rate was 81.13％(43/53)in the observation group and 62.26％(33/53)in the control group.The curative effect of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After four weeks of treatment,the total effective rate was 90.57％(48/53)in the observation group and 73.58％(39/53)in the control group.The curative effect of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(3)After two and four weeks of treatment,the MAS score and upper limb Fugl-Meyer score of the observation group were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the MAS score and upper limb Fugl-Meyer score,the differences were statistically significant(P＜0.05).(4)After two and four weeks of treatment,the BBS score and modified BI Score of the observation group were significantly improved(P＜0.05),and the improvement of BBS score and modified BI score in the observation group was significantly superior to that in the control group,the differences were statistically significant(P＜0.05).(5)There was no significant difference in the incidence of adverse reactions between the observation group and the control group(P＞0.05).Conclusion Ultra-micro acupotomology combined with high and low frequency rTMS in the treatment of upper limb spasm after stroke can significantly improve the clinical symptoms of patients,improve the muscle strength of the upper limbs of patients,the movement and balance ability of the upper limbs,and improve the daily living ability of patients,there being remarkable curative effect.

Objective To explore the selection strategy of diagnostic and therapeutic regimens and assess the efficacy for postoperative infection following internal fixation of patellar fractures. Methods A retrospective analysis was conducted on the clinical data of 12 patients with postoperative infection after internal fixation of patellar fractures. Results A total of 6 patients underwent complete removal of the internal fixation devices during debridement and were subsequently fixed with knee braces, while the other 6 had their original internal fixation devices removed and replaced with Kirschner wire fixation. Three patients developed septic arthritis and underwent knee arthroscopic lavage treatment. All 12 patients underwent bacterial culture and metagenomic next-generation sequencing (mNGS) testing, and the key pathogenic bacteria were successfully identified by mNGS. All wounds achieved primary healing within 2 weeks after closure. At the final follow-up, all patients exhibited good fracture healing, with Böstman patellar fracture function scores ranging from 24 to 29 (mean score of 26.58), and the outcomes were evaluated as excellent in 7 cases and good in 5, resulting in an excellent and good rate of 100.0%. Conclusion For patients with early and delayed postoperative infections following internal fixation of patellar fractures, removal of the internal fixation devices can help reduce the risk of infection recurrence. For patients with concurrent septic arthritis, early diagnosis and timely implementation of arthroscopic joint debridement and irrigation and drainage are crucial.

Objective To evaluate the bioequivalence of test product and reference product in a single dose of amoxicillin clavulanate potassium tablet under fasting and fed conditions in healthy volunteers.Methods An open label,randomized,single dose,four-period,crossover bioequivalence study was designed.Fasting and postprandial tests were randomly divided into 2 administration sequence groups according to 1:1 ratio,amoxicillin clavulanate potassium tablet test product or reference product 375 mg,oral administration separately,liquid chromatography tanden mass spectrometry was applied to determine the concentration of amoxicillin and clavulanate potassium in plasma of healthy subjects after fasting or fed administration,while Phoenix WinNonlin 8.2 software were used for pharmacokinetics(PK)parameters calculation and bioequivalence analysis.Results Healthy subjects took the test product and the reference product under fasting condition,the main PK parameters of amoxicillin are as follows:Cmax were(5 075.57±1 483.37)and(5 119.86±1 466.73)ng·mL-1,AUC0_twere(1.32 × 104±2 163.76)and(1.30 × 104±1 925.11)ng·mL-1,AUC0-∞were(1.32 × 104±2 175.40)and(1.31 ×104±1 935.86)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(3 298.27±1 315.23)and(3 264.06±1 492.82)ng·mL-1,AUC0-twere(7 690.06±3 053.40)and(7 538.39±3 155.89)ng·mL-1,AUC0-∞were(7 834.81±3 082.61)and(7 671.67±3 189.31)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-tand AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Healthy subjects took the test and reference product under fed condition,the main PK parameters of amoxicillin are as follows:Cmax were(4 514.08±1 324.18)and(4 602.82±1 366.48)ng·mL-1,AUC0-twere(1.15 × 104±1 637.95)and(1.15 × 104±1 665.69)ng·mL-1,AUC0-∞ were(1.16 × 104±1 646.26)and(1.15 × 104±1 607.20)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(2 654.75±1 358.29)and(2 850.51±1 526.31)ng·mL-1,AUC0-twere(5 882.82±2 930.06)and(6 161.28±3 263.20)ng·mL-1,AUC0-∞ were(6 022.70±2 965.05)and(6 298.31±3 287.63)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-t and AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Conclusion The two formulations were bioequivalent to healthy adult volunteers under fasting and fed conditions.

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Infant, Newborn ; Humans ; Infant, Premature ; Infant, Low Birth Weight ; Blood Transfusion ; Infant, Premature, Diseases