Pharmaceutical excipients, as an indispensable part of drug preparation, play crucial roles as drug carriers, improving drug release, ensuring drug stability, and enhancing patient compliance. Traditional Chinese Medicine (TCM) boasts a rich developmental history. With the modernization of technology, the deep integration of pharmacy, chemistry, and materials science has provided broader opportunities for innovative research in TCM. Simultaneously, the demand for high-quality excipients has become increasingly critical.This paper aims to review current research and applications of excipients in TCM preparations, including pre-mixed and co-processed excipients, modified excipients, and the unification of drugs and excipients, such as flavoring agents, fillers, penetration enhancers, and delivery systems. A meticulous synthesis and analysis of existing research aims to provide a reference for selecting excipients in TCM preparations, stimulate innovation in excipient development for TCM, and advocate for the development of personalized excipients.

Objective To investigate the relationship between cognitive impairment and sleep parameters in acute ischemic stroke patients with obstructive sleep apnea(OSA).Methods A total of 343 patients with acute ischemic stroke and OSA were selected.The cognitive function was assessed using the simple mental state examination scale(MMSE).Patients were divided into the stroke with OSA and cognitive impairment group(MMSE＜27 points,n=119)and the stroke with OSA without cognitive impairment group(MMSE≥27 points,n=224).General data,TOAST etiological classification and distribution of cerebral infarction lesions were collected.The intelligent sleep monitoring system was used to calculate apnea hypopnea index(AHI)and evaluate OSA.Objective sleep monitoring parameters were collected at night.Sleep monitoring was conducted within 24 h of admission and continuous monitoring for≥3 nights.Continuous monitoring duration≥7 h every night to obtain night sleep structure parameters.Multifactor Logistics regression was used to analyze the relationship between cognitive impairment and sleep parameters in stroke patients with OSA.Results Compared with the stroke with OSA without cognitive impairment group,the proportion of age,diabetes history and HHcy history,the proportion of patients with infarct lesions located in frontal,temporal,parietal,occipital,thalamus,basal ganglia,brainstem and hemioval center increased in the stroke with OSA and cognitive impairment group,and the number of years of education decreased,the number of waking times,the proportion of light sleep and AHI increased,the nighttime sleep efficiency and deep sleep period decreased(P＜0.05).Logistics regression analysis showed that after controlling for years of education,age and other interference factors,nighttime sleep efficiency and AHI were strongly associated with cognitive impairment in acute ischemic stroke patients with OSA(P＜0.05).The increased nighttime sleep efficiency was protective factor for cognitive impairment,and increased AHI was risk factor for cognitive impairment.Conclusion Cognitive impairment in acute ischemic stroke patients with OSA is closely related to sleep parameters,in which the increased sleep efficiency at night is a protective factor for cognitive impairment,and the increased AHI is a risk factor.

Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensi-tivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen"green"natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression.Considering the high GST levels in HCC patients,this compound demon-strated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

Objective:To explore the effect of moderate intensity physical exercise on depression, anxiety and cognitive function of schizophrenic patients and its possible biochemical mechanism.Methods:Totally 148 patients with schizophrenia who were hospitalized in hospital from March 2019 to March 2021 were randomly divided into control group ( n=75) and exercise group ( n=73). The patients of the two groups were given drug treatment and routine exercise according to clinical practice, and the patients in exercise group were given additional medium-intensity physical exercise.Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate the poor mental state of the subjects.The verbal fluency task(VFT), digital span test(DST), trail making test-A(TMT-A) and the positive and negative symptom scale (PANSS) were used to evaluate cognitive function.The levels of endocannabinoids (eCBs) receptors were detected by high performance liquid chromatography, and the levels of monoamine neurotransmitters and eCBs in the patients' serum were determined by enzyme-linked immunosorbent assay (ELISA). SPSS 19.0 software was used for statistical analysis.The measurement data between the two groups were compared by t-test and the counting data between the two groups were compared by χ2 test. Results:(1) After effective intervention, the scores of SAS, SDS, TMT-A and PANSS of the two groups were significantly lower than those before intervention, and the difference before and after intervention between the two groups was statistically significant( t=6.00, 6.52, 25.79, 17.03, all P<0.01). The scores of SAS, SDS, TMT-A and PANSS after intervention in the exercise group were significantly lower than those in the control group( t=4.66, 20.88, 6.61, 8.95; all P<0.01). The number of VFT and DST in the two groups after intervention were significantly higher than those before intervention, and the differences before and after intervention between the two groups were statistically significant( t=13.78, 22.76, both P<0.01). After effective intervention, the number of VFT and DST in exercise group were significantly higher than those in the control group( t=5.02, 5.15, both P<0.01). (2) After effective intervention, the contents of monoamine neurotransmitters and eCBs in serum of the two groups were significantly higher than those before intervention, and HVA level ((63.68±6.99) pg/mL), MHPG level ((175.90±16.22) pg/mL), 5-HIAA level ((29.94±4.19) pg/mL) and CBR1 level ((6.70±1.40)μg/L), 2-AG level ((61.90±5.73)pmol/g) and AEA level ((76.48±6.59) pmol/g) in exercise group were significantly higher than those in the control group ((52.97±5.37)pg/mL, (138.50±11.52)pg/mL, (23.87±3.15)pg/mL, (5.71±1.29)μg/L, (52.13±5.14)pmol/g, (67.66±5.88)pmol/g)( t=10.43, 16.21, 10.91, 8.65, all P<0.01). Conclusion:Moderate intensity physical exercise can significantly improve their depression, anxiety and cognitive function, which may be related to regulating the levels of ECBS and their receptors in patients with chronic schizophrenia to increase monoamine neurotransmitters.

Objective:To investigate the effect of vancomycin (Vm)-loaded microbubbles (MBs) combined with ultrasound targeted microbubble destruction (UTMD) technique on the morphological structure, thickness and bacterial viability of methicillin-resistant Staphylococcus aureus (MRSA) biofilms.Methods:Vm-MBs were prepared by thin film hydration. Sterile coverslips in a diameter of 13 mm were placed in 24-well plates to construct in vitro biofilm models using MRSA as the test strain, and the biofilm morphology was observed by naked eye and light microscopy after crystal violet staining. LIVE/DEAD, SYTO59 and DIL were used to stain biofilms and MBs, respectively. After staining, the biofilm morphology and position of the biofilm in relation to MBs were observed using laser confocal scanning microscopy. The biofilms were divided into control group, Vm group, Vm-MBs group, UTMD group and Vm-MBs+UTMD group according to the random number table method, with 9 samples in each group. After biofilms of each group were treated accordingly for 24 hours, the morphological and structural changes of biofilms in each group were observed using laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining; the difference in biofilm density in each group was measured with the aid of an enzyme marker following crystal violet staining; the difference in biofilm thickness and bacterial viability in each group were observed by laser confocal scanning microscopy. Results:The prepared Vm-MBs met the experimental requirements. The constructed biofilm model observed by naked eye, light microscopy and laser confocal scanning microscopy showed that the biofilm structure was dense with a relatively uniform thickness of (13.8±0.2)nm, a small amount of dead bacteria inside the membrane and the percentage of live bacteria of (94.9±0.3)%. Laser confocal scanning microscopy showed that MBs could penetrate into deeper layers of biofilms. After the respective treatment was given to each group for 24 hours, Laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining showed that the biofilm morphological structure was most significantly disrupted in Vm-MBs+UTMD group compared to control, Vm, Vm-MBs and UTMD groups. In Vm-MBs+UTMD group, a large number of dead bacteria was observed, with only a few scattered planktonic bacteria and irregular changes in cell membrane morphology. Crystal violet staining showed that the biofilm density was significantly lower in Vm-MBs+UTMD group compared to control group ( P<0.05), while the differences between Vm, Vm-MBs and UTMD groups were not statistically significant (all P>0.05). Laser confocal microscopy showed that the biofilm thickness was thinner in Vm-MBs, UTMD and Vm-MBs+UTMD groups compared to control group (all P<0.05), with no significant difference between Vm group and control group ( P>0.05) and that the biofilm thickness was thinner in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), with no significant differences between the other groups (all P>0.05). Bacterial activity in Vm, Vm-MBs, UTMD and Vm-MBs+UTMD groups was significantly lower than that in control group (all P<0.01), with lower in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), but without significant difference between the other groups (all P>0.05). Conclusion:Vm-MBs combined with UTMD technology can effectively destroy the biofilm morphological structure to reduce biofilm thickness. Meanwhile, Vm-MBs combined with UTMD technology can release antibiotics and significantly decrease bacterial viability to improve antibiotic bactericidal efficacy.

OBJECTIVE To compare the phar macokinetics o f ligustrazine hydrochlori de，salvianic acid and rosemarinic acid from Shenxiong glucose injection （SGI）in normal and acute myocardial ischemia （AMI）rats. METHODS Male SD rats were randomly divided into normal group and model group ，with 9 rats in each group. AMI model was established by isoproterenol hydrochloride modeling method. Three rats in each group were selected for model verification. The remaining 6 rats in each group were given SGI （1.2 mL/kg）or equal volum of normal saline via tail vein ；0.3 mL blood was collected through orbital venous bush 0.083，0.167，0.333，0.5，0.75，1，1.5，2，3，5 h after administration. Using luteoloside as internal standard ，the plasma concentrations of ligustrazine hydrochloride ，salvianic acid and rosemarinic acid were determined by ultra performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were fitted by WinNonlin 8.1 software，and statistical analysis was performed by SPSS 18.0 software. RESULTS The linear ranges of ligustrazine hydrochloride ，salvianic acid and rosmarinic acid were 0.06-29.96，0.01-5.15 and 0.006-3.09 μ g/mL（all r＞0.99），respectively. The results of methodological investigation were all in line with the requirements of Chinese Pharmacopoeia （2020 edition）. Compared with normal rats ，CLz of ligustrazine hydrochloride in AMI model rats was significantly increased （P＜0.05）；t1/2 and Vz of salvianic acid were significantly prolonged or increased （P＜0.05）；but the cmax and AUC 0－5 h were significantly decreased （P＜0.05）；AUC0－5 h of rosmarinic acid was significantly decreased （P＜0.05）. CONCLUSIONS The exposure levels of salvianic acid and rosmarinic acid in SGI are lower in AMI model rats than in normal rats ，and the elimination of ligustrazine hydrochloride in AMI model rats is stronger than that in normal rats.

Objective:To identify the gene mutations associated with facial cleft-related orbital hypertelorism in 3 pairs of monozygotic twins with different phenotypes (with/without hypertelorism) and to investigate their mechanisms.Methods:From May 2014 to May 2019, 3 pairs of monozygotic twins, 2 males and 4 females, aged 5-18 years, were treated in Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, one with normal orbital distance and widening of orbital distance was caused by facial fissure. Among the twins, there was 1 case of orbital hypertelorism and the other case of without orbital hypertelorism, and the hypertelorism was caused by facial cleft. To screen for mutations in hypertelorism, whole genome sequencing was performed on 3 pairs of twins. The Sanger method was used to sequence the exons of 33 patients with facial fissure associated hypertelorism and 50 healthy individuals in the same period to identify the genes selected by the whole genome sequencing. The periosteal tissues were obtained from patients and healthy people during plastic surgery. The cells were cultured, the activity of alkaline phosphatase was measured, and the osteogenic differentiation was identified by alizarin red staining, real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expression of signal transduction pathways in periosteal cells.Results:Whole genome sequencing analysis showed that in all three sets of twins, a new synonymous mutation (c.1479G>A, p. Q493Q) was found in the MAML3. In Sanger exon sequencing, 17(51.5%) of 33 patients with hypertelorism carried the mutation, while no mutation was detected in 50 normal controls. The result of periosteum-derived cytology showed that the expression of MAML3 mRNA and protein in the patient-derived cells was lower than that in the healthy-derived cells. Three, 7, 14 days after osteoinduction, the ALP activity in the cells from the patients was higher than that from the healthy subjects (8.540±1.450, 20.740±2.514, 24.090±3.213 vs. 5.268±0.482, 11.680±1.527, 13.200±0.592; all P<0.05). Fourteen days after osteoinduction, the result of alizarin red staining showed that there were more erythema formation in the cells from the patients than those from the healthy subjects, these result suggest that MAML3 mutation may lead to over-differentiation of human periosteal-derived cells. The mRNA and protein expression levels of hes1 and hes5 downstream of the Notch signal pathway were down-regulated in the periosteal cells of the patients, while Wnt3a and β-catenin mRNA and protein expression levels were up-regulated in the Wnt signal pathway. Conclusions:The MAML3 gene (c.1479G>A, p. Q493Q) mutation is one of the causative genes of facial cleft-related hypertelorism. Notch and Wnt/β-catenin signaling pathway play an important role in the pathogenesis of hypertelorism.

Objective:To identify the gene mutations associated with facial cleft-related orbital hypertelorism in 3 pairs of monozygotic twins with different phenotypes (with/without hypertelorism) and to investigate their mechanisms.Methods:From May 2014 to May 2019, 3 pairs of monozygotic twins, 2 males and 4 females, aged 5-18 years, were treated in Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, one with normal orbital distance and widening of orbital distance was caused by facial fissure. Among the twins, there was 1 case of orbital hypertelorism and the other case of without orbital hypertelorism, and the hypertelorism was caused by facial cleft. To screen for mutations in hypertelorism, whole genome sequencing was performed on 3 pairs of twins. The Sanger method was used to sequence the exons of 33 patients with facial fissure associated hypertelorism and 50 healthy individuals in the same period to identify the genes selected by the whole genome sequencing. The periosteal tissues were obtained from patients and healthy people during plastic surgery. The cells were cultured, the activity of alkaline phosphatase was measured, and the osteogenic differentiation was identified by alizarin red staining, real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expression of signal transduction pathways in periosteal cells.Results:Whole genome sequencing analysis showed that in all three sets of twins, a new synonymous mutation (c.1479G>A, p. Q493Q) was found in the MAML3. In Sanger exon sequencing, 17(51.5%) of 33 patients with hypertelorism carried the mutation, while no mutation was detected in 50 normal controls. The result of periosteum-derived cytology showed that the expression of MAML3 mRNA and protein in the patient-derived cells was lower than that in the healthy-derived cells. Three, 7, 14 days after osteoinduction, the ALP activity in the cells from the patients was higher than that from the healthy subjects (8.540±1.450, 20.740±2.514, 24.090±3.213 vs. 5.268±0.482, 11.680±1.527, 13.200±0.592; all P<0.05). Fourteen days after osteoinduction, the result of alizarin red staining showed that there were more erythema formation in the cells from the patients than those from the healthy subjects, these result suggest that MAML3 mutation may lead to over-differentiation of human periosteal-derived cells. The mRNA and protein expression levels of hes1 and hes5 downstream of the Notch signal pathway were down-regulated in the periosteal cells of the patients, while Wnt3a and β-catenin mRNA and protein expression levels were up-regulated in the Wnt signal pathway. Conclusions:The MAML3 gene (c.1479G>A, p. Q493Q) mutation is one of the causative genes of facial cleft-related hypertelorism. Notch and Wnt/β-catenin signaling pathway play an important role in the pathogenesis of hypertelorism.

To study the clinical application value of ultrasound-guided fine needle aspiration biopsy (US-FNAB) and contrast-enhanced ultrasound (CEU) in the diagnosis of thyroid imaging reported and data system Grade 4 (TI-RADS 4) nodules.
 Methods: A retrospective analysis of 134 patients with thyroid nodules surgery were selected, and their results of preoperative color Doppler ultrasonography were TI-RADS 4. The data of US-FNAB and CEU before operation and the results of pathological section after operation were collected. The pathological results were taken as the gold standard, and the specimens obtained by US-FNAB puncture were used for HE staining and cytological diagnosis. The sensitivity, specificity, accuracy and the cost were calculated for CEU and US-FNAB, respectively. The diagnostic efficacy of the 2 methods was compared.
 Results: Of 134 thyroid nodules, there were 131 malignant nodules (97.76%) and 3 benign ones (2.24%). The sensitivity of US-FNAB and CEU were 87.02% and 93.89% respectively. The specificity of US-FNAB and CEU were 100.00% and 66.67%. The accuracy of US-FNAB and CEU were 87.31% and 93.28% respectively. Comparisons of the diagnostic accuracy were performed by χ2 test. There was no significant difference in sensitivity between CEU and US-FNAB (P>0.05). However, the sensitivity of US-FNAB and CEU were 87.50% and 100.00%, respectively, when the maximum diameter of nodule was less than 10 mm, and there was statistical significance (P<0.05). The sensitivity of US-FNAB and CEU were 92.73% and 85.45%, respectively, when the maximum diameter of nodule was more than 10 mm, and there was no statistical significance (P>0.05). The cost and risk of US-FNAB was higher than those of CEU.
 Conclusion: The sensitivity of US-FNAB is higher than that of CEU for thyroid nodules with the diameter larger than 10 mm. With high detection rate, good safety and low cost, CEU can still be used for thyroid nodules with the diameter less than 10 mm, which is diagnosed as negative nodules by US-FNAB.
Biopsy, Fine-Needle ; Data Systems ; Humans ; Retrospective Studies ; Sensitivity and Specificity ; Thyroid Neoplasms ; Thyroid Nodule

Objective To survey the distribution pattern and subject domain knowledge of the literatures about ventilator-associated pneumonia (VAP). Methods Literatures about VAP published until December 2017 were identified in SinoMed database for statistics and analysis. The information of author, organization and province was extracted by BICOMS software for generating co-occurrence matrix, at the same time, the topic words were cluster analyzed by Gcluto software to generate topical visual surface maps and visualization matrices, and the current research hotspots were analyzed. NetDraw from Ucinet 6.0 software was used to arrange the relationship among topic words according to the centrality, and the social network diagrams of authors, authors' provinces and institutions were draw to analyze the current status of VAP research cooperation. Results 4 851 VAP-related literatures were retrieved preliminarily, and 43 were excluded from abstracts, news reports, information and missing literatures. Finally, a total of 4 808 articles were enrolled in the visual analysis. From 2001 to 2004, the number of VAP-related literatures published was less than 10. Since 2009, the number of VAP documents had increased steadily, from 2010 to 2017, the peak period of publications reached 91.7% (4 411/4 808). According to the analysis of the amount of publications, the top three of 34 provincial administrative regions that published VAP-related literature in China were Guangdong Province (n = 628), Jiangsu Province (n = 478) and Zhejiang Province (n = 404), the number of hospitals issued by the First Affiliated Hospital of Chongqing Medical University was the largest (n = 20); there was only one journal with more than 100 articles, and there were 154 journals with only one article, accounting for 34.8% of the total number of journals. A total of 9 921 authors participated in the VAP-related literature writing, the number of high-yielding authors was not large, and the institution could not establish an effective social network diagram, suggesting that communication and cooperation should be strengthened in hospitals and outside hospitals. The results of the topic words social network analysis showed that the VAP research field was centered around the core of "mechanical ventilation", "intensive care unit (ICU)", "risk factor analysis", "nursing", "etiological analysis", "preventive measures" and "pathogens". The current research hotspots were at the edge of the network map, such as "drug sensitivity analysis", "Acinetobacter baumannii", "bronohoalveolar lavage (BAL)" and "acute exacerbation of chronic obstructive pulmonary disease (AECOPD)". By clustering 80 high-frequency topic words, at present, VAP research hotspots were mainly focus on five topics: obstructive pulmonary disease, especially in acute exacerbation, was prone to VAP; concerned about newborns and children's VAP; types, drug resistance and selection of antimicrobial agents for VAP pathogens in ICU; clinical efficacy and prognosis of VAP through preventive measures, pulmonary supportive care and comprehensive care interventions; oral care and airway management during mechanical ventilation was also the key aspect of the treatment of VAP. Conclusions In recent years, the academics had attached great importance to the study of VAP, the number of publications had reached a historical peak, and the research direction was diverse. However, it was necessary to strengthen cooperation among research institutes, collect and count epidemiological data, improve and expand the research quality and scale of clinical diagnosis, nurse, prevention, pathogen distribution and drug resistance analysis.