[摘 要] 甲状腺癌是内分泌系统中最为常见的恶性肿瘤，近年来其发病率呈现出显著的上升趋势。乙酰化修饰作为一种重要的蛋白质翻译后修饰，参与调控各个类型甲状腺癌相关基因的转录表达、细胞周期进程及侵袭能力。组蛋白去乙酰化酶（HDAC）抑制剂在甲状腺癌治疗中显示出潜在的应用前景。本文通过调研近年来相关文献，系统回顾了乙酰化修饰在参与甲状腺癌发生发展过程中的生物学功能及其调控机制，进一步探讨HDAC抑制剂在临床治疗中的应用前景，为甲状腺癌的靶向治疗提供坚实的理论依据和提出可行的治疗策略。

Objective: To examine the association of joint effect of overweight and obesity with dyslipidemia on left ventricular hypertrophy (LVH) in children, so as to provide scientific evidence for the prevention of early cardiovascular damage in children. Methods: Data were obtained from the second followup crosssectional survey of Huantai Childhood Cardiovascular Health Cohort study in 2021, comprising 1 047 children aged 10-15 years with complete information. Based on overweight and obesity status and dyslipidemia status, all participants were divided into four groups:normal weight with normal lipid levels, normal weight with dyslipidemia, overweight and obesity with normal lipid levels, and overweight and obesity with dyslipidemia. Left ventricular mass index (LVMI) levels and prevalence of LVH across four groups were compared. Multivariate Logistic regression model was used to examine the association of joint effect of overweight and obesity with dyslipidemia on LVH in children. Results: There were significant differences in LVMI levels [(28.66±7.10, 29.63±4.71,31.49±5.86,32.65±4.80)g/m2.7] and prevalence of LVH (4.28%, 12.50%, 22.74%, 31.30%) across four groups (F/χ2=50.76, 90.92, P<0.05). After adjustment for confounding variables such as gender,age,screen time,sleep duration,fruit and vegetable intake,carbonated beverage consumption,physical activity and elevated blood pressure, compared to children with both normal weight and normal lipid levels, the risk of LVH in children with dyslipidemia alone increased (OR=3.27, 95%CI=1.57-6.82，P<0.05). Children with overweight and obesity alone also had a significantly increased risk of LVH (OR=6.33, 95%CI=3.76-10.66), and the highest risk was observed in those with both overweight and obesity with dyslipidemia (OR=9.66, 95%CI=5.35-17.43) (P<0.05). Conclusions The joint effect of overweight and obesity with dyslipidemia is positively correlated with LVH in children. To prevent LVH in children, both overweight and obesity with dyslipidemia should be paid attention to.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

By reviewing the research history on quality comparison between wild and cultivated Chinese crude drugs， this paper systematically combed the relevant research reports since the 1950s， and summarized and analyzed the results of existing comparative studies， and found that the existing comparative research on the quality of wild and cultivated Chinese crude drugs were mainly focused on several aspects， including characteristics， microstructures， chemical compositions， pharmacodynamic effects， and genetic diversity. Among these， comparative studies of chemical compositions have been the dominant approach， with a particular emphasis on comparing the contents of index components. However， research on pharmacodynamic effects remained relatively limited. Due to various factors such as sample quantity， sample origin， growth period and cultivation methods， the differences in quality between wild and cultivated Chinese crude drugs vary significantly. In general， most wild Chinese crude drugs exhibited higher quality than cultivated products， with significant differences in their characteristics. The contents and proportions of some chemical components underwent noticeable changes， particularly with a marked increase in the proportion of primary metabolites after cultivation. The quality of cultivated Chinese crude drugs is closely related to the cultivation practices employed. Chinese crude drugs produced through wild nurturing， simulated wild planting， ecological cultivation， and other similar methods demonstrate quality levels comparable to those of wild Chinese crude drugs. Based on the analysis results， it is recommended to explicitly specify the cultivation practices and cultivation period of cultivated Chinese crude drugs in comparative studies of the quality between wild and cultivated Chinese crude drugs. Multiple technical approaches， including characteristics， microscopy， non-targeted metabolomics combined with quantitative analysis of differential components， and bioefficacy evaluation， should be employed to comprehensively assess the quality disparities between wild and cultivated Chinese crude drugs. Moreover， research efforts should be intensified to investigate the changes in pharmacodynamic effects resulting from differences in plant cell wall composition， primary metabolites， and secondary metabolites， in order to guide the production of high-quality Chinese crude drugs.

ObjectiveBased on the traditional quality evaluation methods summarized in previous dynasties， this paper systematically contrasted cultivated Astragali Radix（CA） and wild-simulated Astragali Radix（WA） from the aspects of character， microstructure and chemical composition by modern technological means. MethodThe collected CA and WA were compared in characters and microscopic characteristics in cross section， and comparative analysis were performed on the contents of cellulose， extracts， carbohydrate， total flavonoids， total saponins， etc. Then ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometer（UPLC-Q-TOF-MS） and desorption electrospray ionization mass spectrometry imaging（DESI-MSI） were used to comparatively analyze the secondary metabolites and their spatial distributions in the xylem and phloem of CA and WA. ResultIn terms of characters， the characters and sectional features of WA was consistent with the characteristics of high-quality Astragali Radix， while the CA was quite different from the traditional high-quality Astragali Radix. In terms of microscopy， the phellem layer of CA was thin， and the section fissures were mostly distributed through the cambium in a long strip shape without obvious growth ring characteristics. The cork layer of WA was thick， and the cracks in the section were distributed in the center of the xylem and the outer edge of the phloem in an irregular cavity shape. The cambium was tight without cracks， and had obvious characteristics of a growth ring. In terms of chemical composition， the contents of water-soluble extract， 80% ethanol extract and sucrose of CA was significantly higher than those of WA， while the contents of total saponins， lignin and hemicellulose were significantly lower than those of WA. And the contents of 100% ethanol extract， total polysaccharides and total flavonoids in both of them were generally similar， but slightly higher in WA. The contents of 2 kinds of monoacyl-substituted flavonoid glycosides in the xylem of WA was significantly higher than those of CA， while the contents of 2 kinds of flavonoid aglycones and one flavonoid glycoside were on the contrary. The contents of 7 saponins in phloem of WA were significantly higher than those of CA. ConclusionThere are significant differences between CA and WA in characters， microstructure and chemical components， in which CA has a fast growth rate and a short planting period， and the primary metabolites such as water-soluble extracts and sucrose are more enriched， which is the reason for its firm texture and sweetness being significantly higher than those of WA. However， the contents of lignin， hemicellulose and some secondary metabolites in WA are significantly higher than those in the CA， which are close to the traditional description of characters and quality. Based on the results of this study， it is suggested to strengthen the production of WA， improve the supply capacity of WA， and gradually upgrade the current standard. It is recommended to increase the contents of monoacyl-substituted flavonoid glycosides， total saponins and other indicators that can characterize different production methods， so as to guide the high-quality production of Astragali Radix.

ObjectiveBased on the experience of traditional quality evaluation， the quality of Atractylodis Macrocephalae Rhizoma（AMR） with different production methods such as direct seeding， transplanting after seedling raising， topping and non-topping， and difference in growth years was compared. MethodVernier caliper was used to measure the trait data of AMR in different production methods. Paraffin sections of AMR with different production methods were made by saffron solid green staining， and the microstructure was observed. The contents of water-soluble and alcohol-soluble extracts in AMR with different production methods were determined according to the 2020 edition of Chinese Pharmacopoeia. The content of water-soluble total polysaccharides in AMR with different production methods was detected by sulfuric acid-anthrone method. Fiber analyzer was used to detect the content of fiber components in AMR with different production methods. The contents of monosaccharides， oligosaccharides and some secondary metabolites in AMR with different production methods were detected by ultra performance liquid chromatography（UPLC）， and the differences of chemical components were compared by multivariate statistical analysis methods such as principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）. ResultIn terms of traits， the 3-year-old AMR with direct seeding and without topping was close to the high-quality AMR with "phoenix-head and crane-neck， strong sweetness and clear aroma" recorded in ancient materia medica， followed by the 3-year-old AMR with topping after transplanting， while the 2-year-old AMR with topping after transplanting with high market circulation rate was generally fat and strong with mild odor. In the microscopic aspect， the arrangement of xylem vessels and fiber bundles in the 3-year-old samples formed two obvious rings. Compared with the 2-year-old samples cultivated in Bozhou and Zhejiang， the 3-year-old samples without topping after transplanting had more wood fibers. In terms of chemical composition， the contents of 70% ethanol extract， fructose， glucose， sucrose， 1-kestose， atractylenolide Ⅰ， chlorogenic acid， neochlorogenic acid， cryptochlorogenic acid and other components in 3-year-old AMR with direct seeding and without topping were significantly higher than those in the other three samples（P<0.05）. The contents of cellulose， 70% ethanol extract， sucrose， atractylenolide Ⅰ， atractylone and other components in 3-year-old AMR with topping after transplanting were significantly higher than those in the 2-year-old AMR with high market circulation rate（P<0.05）， while the contents of water-soluble extract and water-soluble total polysaccharides in 2-year-old samples with topping after transplanting were significantly higher than those in the 3-year-old AMR with topping after transplanting， direct seeding and without topping（P<0.05）. ConclusionUnder the current mainstream production mode， too much manual intervention makes AMR heavily enriched in polysaccharides and increased the yield， but the accumulation of sweet substances， fragrant substances and fiber substances is insufficient， which affects its quality. The current quality standard of AMR has some shortcomings in guiding the high quality production of it， it is suggested to revise the quality standard of AMR， supplement the quantitative analysis of secondary metabolites， and strengthen the production of imitation wild AMR.

Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.

Objective To develop a physiological pharmacokinetic(PBPK)model of ritonavir,simulate ritonavir-mediated drug interactions,and provide future predictions for ritonavir pharmacokinetics(PK)and drug-drug interaction(DDI).Methods The PBPK model of ritonavir was constructed by searching relevant databases,collecting data on the physicochemical properties,PK,DDI related parameters and clinical studies of ritonavir,and using PK-Sim software to optimize and validate the parameters of the model to evaluate the performance of the constructed PBPK model in describing the PK characteristics and predicting the DDI of ritonavir.Results The ritonavir PBPK model demonstrated good performance,and by calculating the geometric mean folded error(GMFE)between the Sim and actual Obs values,the GMFEs of ritonavir AUC and Cmax were 1.11 and 1.16,respectively,and the GMFEs of ritonavir AUC and Cmax after combination with ritonavir were 1.24 and 1.26,respectively.Conclusion The PBPK model of ritonavir has been successfully constructed,and the effect of ritonavir on the metabolic enzyme cytochrome P450 3A4 is significant.Therefore,when ritonavir is combined with the victim drugs,individualized dosing can be guided according to the PBPK model.