ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

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 observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To observe the effect of omeprazole enteric-coated capsules on clinical symptoms and serum inflammatory factor levels in children with chronic gastritis and peptic ulcer.Methods Children with chronic gastritis and peptic ulcer were divided into treatment group and control group by random number table method.The control group was given triple therapy of ranitidine hydrochloride tablets,amoxicillin and clarithromycin,while the treatment group was treated with omeprazole enteric-coated capsules combined with amoxicillin and clarithromycin.Clinical efficacy,symptom relief time,and changes in serum motilin(MOT),gastrin(GAS)and inflammatory factors[interlrukin-6(IL-6)and interlrukin-8(IL-8)]were compared between the two groups.Results There were 48 cases in treatment group and 48 cases in control group.After treatment,the total effective rates in treatment group and control group were 93.74％(45 cases/48 cases)and 85.42％(41 cases/48 cases),with significant difference(P＜0.05).After treatment,the disappearance time of ulcer induced pain in treatment group and control group were(1.51±0.26)and(2.08±0.42)d;the disappearance time of acid regurgitation were(2.29±0.40)and(2.93±0.33)d;the disappearance time of burning sensation were(2.37±0.21)and(2.85±0.54)d;the length of hospital stay were(6.21±1.07)and(6.94±1.25)d;serum MOT levels were(298.48±35.15)and(273.58±31.25)pg·mL-1;serum GAS levels were(167.28±19.46)and(128.32±18.61)ng·L-1;IL-6 levels were(58.67±5.39)and(76.14±6.63)mg·mL-1;IL-8 levels were(50.08±5.16)and(58.68±5.49)mg·mL-1.The above indexes were significantly different between control group and treatment group(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 8.33％and 12.50％,with no statistical significance(P＞0.05).Conclusion Omeprazole enteric-coated capsules in the treatment of children with chronic gastritis and peptic ulcer can effectively alleviate various clinical symptoms and improve clinical efficacy.At the same time,it can lower serum levels of inflammatory factors and improve inflammation,with good effect.

Objective To explore the protective mechanism of icariin on neuronal oxidative damage,providing a basic pharmacological basis for the treatment of cognitive impairment.Methods Glutamate was used to induce oxidative stress injury in HT22 cells.HT22 cells were divided into control group(normal cultured cells),model group(glutamate injury model)and experimental-L,-M,-H groups(5,10 and 20 μmol·L-1 icariin pretreatment for modeling,respectively).Cell proliferation was detected by cell counting kit-8(CCK-8)method;cytotoxicity was detected by lactate dehydrogenase(LDH)method;reactive oxygen species(ROS)levels were detected by flow cytometry;superoxide dismutase(SOD)levels were detected by biochemical kits;the expression levels of Kelch-like epichlorohydrin-related protein-1(Keap1),nuclear factor E2-related factor 2(Nrf2)were detected by Western blotting;the corresponding mRNA expression was detected by real-time fluorescence quantification polymerose chain reaction.Results The cell viability of control group,model group and experimental-L,-M,-H groups were(100.00±1.31)％,(66.38±2.44)％,(72.07±4.95)％,(82.41±3.57)％and(87.97±4.98)％;LDH release were(0.48±0.52)％,(18.82±2.09)％,(15.32±1.17)％,(10.37±1.39)％and(6.51±0.87)％;ROS level were(14.23±1.13)％,(41.74±1.60)％,(35.69±1.08)％,(33.28±1.69)％and(30.32±2.03)％;SOD levels were(54.84±1.17),(37.95±1.13),(48.02±1.28),(50.56±1.34)and(52.55±1.04)U·mg-1;Keap1 protein levels were 0.36±0.01,0.52±0.03,0.46±0.04,0.39±0.09 and 0.35±0.12;Nrf2 protein levels were 0.29±0.02,0.13±0.08,0.18±0.03,0.21±0.11 and 0.26±0.04;catalase(CAT)mRNA levels were 1.01±0.08,0.81±0.06,0.90±0.04,1.05±0.15 and 1.33±0.26;SOD mRNA levels were 1.09±0.12,0.83±0.03,0.86±0.08,0.94±0.08 and 1.09±0.16.Among the above indicators,the differences between the model group and the control group were statistically significant(all P＜0.01);the differences between the experimental-M,-H groups and the model group were statistically significant(P＜0.01,P＜0.05).Conclusion Icariin may activate the Keap1/Nrf2/antioxidant response element(ARE)signaling pathway,regulate the expression of related proteins,and reduce the level of ROS to effectively alleviate oxidative stress injury in neuronal cells.

Objective To explore the role of resveratrol in the immune response and proliferation of macrophages induced by homocysteine(Hcy).Methods ANA-1 cells were divided into control group(conventional culture),model group(100 μmol·L-1 Hcy),experimental-L,-M,-H groups(adding 25,50 and 100 μmol·L-1 resveratrol to model group,respectively),Hcy+Ad-SIRT1 group(100 μmol·L-1 Hcy+Ad-SIRT1),Hcy+si-FOXO1 group(100 μmol·L-1 Hcy+si-FOXO1),Hcy+Res-L+Ad-SIRT1+si-FOXO1 group(100 μmol·L-1 Hcy+25 μmol·L-1 Resveratrol transfected with Ad-SIRT1+si-FOXO1).The cell proliferation was detected by methyl thiazolyl tetrazolium(MTT),and the concentration of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the supernatant of cell culture medium was detected by enzyme-linked immunosorbent assay.The gene and protein expression of silencing information regulator 1(SIRT1)and forkhead protein 01(FOXO1)were detected by Western blot.Results The optical density of 450 nm in control group,model group and experimental-L,-M,-H groups were 0.25±0.02,0.36±0.02,0.33±0.01,0.30±0.02 and 0.29±0.01,respectively.Compared with the control group,the cell proliferation in the model group was significantly increased(P＜0.05).Cell proliferation in experimental-L,-M,-H groups was significantly decreased compared with model group(all P＜0.05).IL-6 in the supernatant of cell culture medium of control group,model group and experimental-L group were(394.04±20.06),(614.23±21.09)and(501.53±16.52)pg·mL-1,respectively;TNF-α were(516.54±18.96),(717.22±24.81)and(632.74±19.11)pg·mL-1,respectively;SIRT1 relative protein expression were(1.00±0.05),(0.57±0.05)and(0.77±0.04),respectively;the relative protein expression of FOXO1 were 1.00±0.05,2.31±0.18 and 1.58±0.11,respectively.Compared with the control group,the above indexes in the experimental-L group had statistical significance(all P＜0.05).The contents of IL-6 and TNF-α in cell culture fluid supernatant in model group,experimental-L group,Hcy+Ad-SIRT1 group and Hcy+si-FOXO1 group were significantly lower than those in model group,with statistical significance(all P＜0.05).After co-transfection with Ad-SIRT1 and si-FOXO1,the contents of IL-6 and TNF-α in cell culture medium superserum of experimental-L group were significantly lower than those of Ad-SIRT1 group and si-FOXO1 group(all P＜0.05).Conclusion Resveratrol can attenuate the immune response and proliferation of macrophages induced by Hcy,which may be related to the alteration of SIRT1/FOXO1 pathway.

ObjectiveTo investigate the effects of berbamine hydrochloride on sorafenib resistance in hepatocellular carcinoma cells and the underlying mechanisms. MethodThe sorafenib-resistant cell line SMMC-7721/S was selected by the concentration increment method starting at 1.25 μmol·L^-1 sorafenib. Both SMMC-7721 and SMMC-7721/S cells were treated with 0， 2.5， 5， 10， 15， 20 μmol·L^-1 sorafenib， and the cell counting kit-8 （CCK-8） assay was employed to determine the half maximal inhibitory concentration （IC₅₀） and calculate the resistance index （RI）. Western blot was conducted to compare the expression of proteins involved in autophagy and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway between SMMC-7721 and SMMC-7721/S cells. Furthermore， SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 2.5， 5， 10 μmol·L^-1 sorafenib， and the cell growth was assessed by the CCK-8 assay. In addition， SMMC-7721 and SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 5 μmol·L^-1 sorafenib， and the cell proliferation was examined by the colony formation assay. The immunofluorescence assays with Microtubule-associated protein 1 light chain 3 （LC3） and LysoTracker as probes were employed to assess the lysosomal acidification in SMMC-7721 cells treated with 5 μmol·L^-1 berbamine hydrochloride or 0.1 μmol·L^-1 autophagy inhibitor bafilomycin A1 （Baf）. Further， the expression of proteins involved in autophagy and PI3K/Akt/mTOR signaling pathway was determined by Western blot and compared between groups. ResultSorafenib showed the IC₅₀ of 9.56 mol·L^-1 （P<0.01） and 7.99 mol·L^-1 for SMMC-7721/S and SMMC-7721 cells， respectively， at 24 h. The resistance index （RI） of SMMC-7721/S for sorafenib was 1.20 （P<0.01）， which indicated mild resistance. Compared with SMMC-7721 cells， SMMC-7721/S cells exhibited up-regulated expression of p-mTOR， p-Akt， and LC3Ⅱ， down-regulated expression of p62 protein （P<0.01）， and unchanged Akt protein level. CCK-8 and colony formation assays demonstrated that the combination of berbamine hydrochloride and sorafenib exhibited a synergistic effect （Q>1.15）， with berbamine hydrochloride partially reversing the resistance of liver cancer cells to sorafenib. The immunofluorescence detection of LC3 revealed that berbamine hydrochloride and Baf significantly increased LC3 in SMMC-7721 cells. The detection with LysoTracker as the probe showed that berbamine hydrochloride inhibited the acidity of lysosomes in SMMC-7721 cells （P<0.01）， indicating the suppression of autophagy. Berbamine hydrochloride further enhanced the downregulation of p-mTOR and p-Akt protein levels and did not change the Akt protein level in SMMC-7721 cells exposed to sorafenib. Berbamine hydrochloride inhibited the increase in p-mTOR expression， down-regulated the p-Akt protein level， and did not change the total Akt protein level in the SMMC-7721/S cells exposed to sorafenib. ConclusionBerbamine hydrochloride can ameliorate the resistance of liver cancer cells to sorafenib by inhibiting cellular autophagy and the PI3K/Akt/mTOR signaling pathway.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Additive manufacturing(3D printing)technology aligns with the direction of precision and customization in future medicine,presenting a significant opportunity for innovative development in high-end medical devices.Currently,research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants.Primary areas including metallic orthopaedic implants,polyether-ether-ketone(PEEK)bone implants,and biodegradable implants have been developed for clinical and industrial application.Recent research achievements in these areas are reviewed,with a discussion on the additive manufacturing technologies and applications for customized implants.Challenges faced by different types of implants are analyzed from technological,application,and regulatory perspectives.Furthermore,prospects and suggestions for future development are outlined.

Objective:To investigate the vaccination status, characteristics and prognosis of patients suffering from a combination of COVID-19 and chronic lymphocytic anemia (CLL) in China.Methods:Clinical data of 328 patients with chronic lymphocytic leukemia (CLL) who were first diagnosed with COVID-19 and treated in the Department of Hematology of Jiangsu Provincial People’s Hospital between November 2022 and February 2023 were retrospectively analyzed. Univariate and multivariate analysis of data of patients with severe/critical COVID-19 were conducted by applying the binary logistic regression model.Results:The median age of the CLL patients was 60 (24-87) years. 23.5% (77/328) of these patients suffered from severe/critical COVID-19 infection. Univariate analysis of the data demonstrated that a combination of factors including age >67 years ( OR=2.15, 95% CI 1.24- 3.73, P=0.006), diabetes ( OR=2.09, 95% CI 1.05-4.20, P=0.037), chronic hepatitis B ( OR=2.91, 95% CI 1.30-6.51, P=0.010), CLL progressive ( OR=3.79, 95% CI 1.57-9.15, P=0.003) and CD20 antibody-based treatments within three months prior to the COVID-19 infection ( OR=2.79, 95% CI 1.35-5.77, P=0.006) were the risk factors for severe/critical COVID-19. According to the multivariate analysis, CLL progressive ( OR=2.98, 95% CI 1.10-8.10, P=0.033) was an independent risk factor for severe/critical COVID-19 and administration of the BTK (Bruton tyrosine kinase) inhibitor monotherapy might exert a protective effect and influence a positive outcome of the COVID-19 infection ( OR=0.38, 95% CI 0.16-0.90, P=0.028). Among the 242 patients who were followed up until October 2023, 9.1% (22/242) had multiple subsequent COVID-19 infections (≥3), and 2.1% (5/242) had persistent COVID-19 infections (patients with persistent positive test for the SARS-CoV-2 antigen testing until missing follow-up for any reason). The peak value of the anti-SARS-CoV-2-IgG titres was observed between three and four months post symptom onset (median: 3.511 S/CO vs 1.047 S/CO, P<0.05). The levels of immunoglobulin A gradually decreased following infection with COVID-19, and its trough levels were attained between two to four weeks post infection (median: 0.30 g/L vs 0.74 g/L, P<0.05). According to this study the mortality of patients suffering from a combination of COVID-19 infection and CLL was 2.7% (9/328), and the main reason for their death was respiratory failure and heart failure. Conclusions:A low rate of COVID-19 vaccination and a high rate of severe/critical COVID-19 infection was observed in the CLL patients. CLL progressive was associated with severe/critical COVID-19. Anti-CD20-based treatments received within the past three months might be a risk factor for exacerbation of COVID-19 infection, whereas a monotherapy with BTK inhibitors exert a protective effect and improve outcome of COVID-19 infection.