ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

Objective To evaluate the feasibility of process scale-up for the production of human prothrombin complex concentrate(PCC) by comparing the quality parameters of PCC samples obtained at different stages of process scale-up.Methods The PCC production process was scaled up sequentially through bench scale, pilot scale and production scale.Samples were collected at critical process control points across the three scales for comparative quality analysis. The final PCC products from each scale were tested in accordance with the Chinese Pharmacopoeia(VolumeⅢ, 2020 edition) to assess process stability and regulatory compliance during scale-up.Results After the first ultrafiltration step, no statistically significant differences were observed in the potency of human coagulation factor Ⅸ(FⅨ) or protein content among samples from the three scales(F = 1. 066 and 0. 590, respectively, each P > 0. 05). The FⅨ recovery rates were(69. 3 ± 10. 3)%,(73. 9 ±11. 1)%, and(69. 8 ± 7. 3)%, respectively, with no significant difference( F = 0. 330, P > 0. 05). Following solvent/detergent(S/D) treatment, the pH remained stable, and no significant differences were observed in FⅨ potency or protein content(F =1. 414 and 0. 542, respectively, each P > 0. 05). After the secondary ion-exchange chromatography step, no significant differences were found in FⅨ potency or specific activity(F = 0. 437 and 0. 201, respectively, each P > 0. 05), with FⅨ recovery rates of(90. 6 ± 6. 7)%,(82. 6 ± 4. 6)% and(87. 2 ± 6. 1)%, respectively, with no significant difference(F = 2. 513, P > 0. 05).At the bulk solution stage, no significant differences were observed in FⅨ potency or specific activity(F = 0. 187 and 0. 135,respectively, each P > 0. 05) with stable pH, and FⅨ recovery rates were(90. 6 ± 7. 5)%,(97. 2 ± 8. 3)%, and(92. 2 ± 6. 4)%,respectively, with no significant difference(F = 1. 016, P > 0. 05). After dry-heat virus inactivation, no significant differences were noted in the potency of factorsⅡ, Ⅶ, Ⅸ, and Ⅹ(F = 0. 11, 0. 473, 0. 818, and 0. 244, respectively, each P > 0. 05).The critical quality attributes of final PCC products from all three scales were consistent and complied with the requirements of Chinese Pharmacopoeia(Volume Ⅲ, 2020 edition).Conclusion The established PCC production process is stable, reliable, and reproducible, demonstrating the feasibility of process scale-up.

Objective To compare the quality and centrifugal efficiency of human plasma cryoprecipitates extracted by GQ142 high-speed tube centrifuge and BKB45 continuous flow centrifuge and the differences in the production process of human coagulation factor Ⅷ(FⅧ).Methods The main functions, parameters and work efficiency of GQ142 high-speed tube centrifuge and BKB45 continuous flow centrifuge were compared. Cryoprecipitates were extracted for FⅧ production,sampling and testing, comparing the quality, yield, and virus safety of cryoprecipitates, as well as the quality and virus safety of FⅧ production process and finished products.Results Compared with GQ142 high-speed tube centrifuge, BKB45 continuous flow centrifuge had more perfect functions and higher working efficiency. The appearance of the cryoprecipitates extracted by both centrifuges was normal, the virus safety was in accordance with the internal quality control standard, and there was no statistically significant difference in cryoprecipitates yield(t = 1. 507, P > 0. 05). The recovery rates of FⅧactivity were(48. 7 ± 4. 2)% and(49. 2 ± 5. 4)%, respectively, with no statistically significant difference(t =-0. 250, P >0. 05). There was no statistically significant difference in FⅧ potency, protein content and FⅧ specific activity among cryoprecipitate solution, post chromatographic products and ultrafiltration products(t =-1. 466,-2. 084,-0. 998,-1. 701,-1. 973, 0. 472,-0. 975, 1. 116, and-1. 215, respectively, each P > 0. 05). The recovery rates of FⅧ activity of post chromatographic products were(38. 0 ± 4. 4)% and(38. 7 ± 5. 6)%, respectively, with no statistically significant difference(t =-0. 275, P > 0. 05). The pH of ultrafiltration products was stable. The appearance of the finished products was normal, and the virus safety indicators, FⅧ potency, moisture, pH, protein content and FⅧ specific activity were all in accordance with the quality standards of Chinese Pharmacopoeia(Vol Ⅲ, 2020 edition).Conclusion Compared with GQ142 high-speed tube centrifuge, BKB45 continuous flow centrifuge can significantly improve production efficiency while ensuring the quality of cryoprecipitates and FⅧ, making it suitable for large-scale production.

Objective To compare the quality and centrifugal efficiency of human plasma cryoprecipitates extracted by GQ142 high-speed tube centrifuge and BKB45 continuous flow centrifuge and the differences in the production process of human coagulation factor Ⅷ(FⅧ).Methods The main functions, parameters and work efficiency of GQ142 high-speed tube centrifuge and BKB45 continuous flow centrifuge were compared. Cryoprecipitates were extracted for FⅧ production,sampling and testing, comparing the quality, yield, and virus safety of cryoprecipitates, as well as the quality and virus safety of FⅧ production process and finished products.Results Compared with GQ142 high-speed tube centrifuge, BKB45 continuous flow centrifuge had more perfect functions and higher working efficiency. The appearance of the cryoprecipitates extracted by both centrifuges was normal, the virus safety was in accordance with the internal quality control standard, and there was no statistically significant difference in cryoprecipitates yield(t = 1. 507, P > 0. 05). The recovery rates of FⅧactivity were(48. 7 ± 4. 2)% and(49. 2 ± 5. 4)%, respectively, with no statistically significant difference(t =-0. 250, P >0. 05). There was no statistically significant difference in FⅧ potency, protein content and FⅧ specific activity among cryoprecipitate solution, post chromatographic products and ultrafiltration products(t =-1. 466,-2. 084,-0. 998,-1. 701,-1. 973, 0. 472,-0. 975, 1. 116, and-1. 215, respectively, each P > 0. 05). The recovery rates of FⅧ activity of post chromatographic products were(38. 0 ± 4. 4)% and(38. 7 ± 5. 6)%, respectively, with no statistically significant difference(t =-0. 275, P > 0. 05). The pH of ultrafiltration products was stable. The appearance of the finished products was normal, and the virus safety indicators, FⅧ potency, moisture, pH, protein content and FⅧ specific activity were all in accordance with the quality standards of Chinese Pharmacopoeia(Vol Ⅲ, 2020 edition).Conclusion Compared with GQ142 high-speed tube centrifuge, BKB45 continuous flow centrifuge can significantly improve production efficiency while ensuring the quality of cryoprecipitates and FⅧ, making it suitable for large-scale production

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Objective To explore the impact of high glucose(HG)intervention on immune escape of pancreatic cancer cells and its molecular mechanisms.Methods PANC-1 cells were treated with different concentrations of glucose(0,7.5,15,30 mmol/L)for 24 h to establish high glucose intervention PANC-1 cells.miR-429 mimics and its negative control(mimics NC)were transfected into PANC-1 cells,which were divided into control group,HG group,HG+mimics NC group,HG+mimics group,HG+mimics+oe-NC group,and HG+mimics+oe-ZEB1 group.Flow cytometry was utilized to measure the expression level of cell surface molecule PD-L1;qRT-PCR was used to detect the expression levels of miR-429 and ZEB1 mRNA in cells;Western blot was used to detect the ex-pression level of ZEB1 protein in cells.The above-mentioned PANC-1 cells from each group were co-cultured with CD8+T cells to establish a co-culture system,and CCK-8 was used to assess cell proliferation activity;apoptosis levels of cells were measured using flow cytometry;lactate dehydrogenase(LDH)release assay was used to detect the killing effect of CD8+T cells on PANC-1 cells;dual-luciferase reporter system was used to validate the target-regulatory relationship between mi R-429 and ZEB1.Results HG could promote the expression of cell surface mole-cules PD-L1 and ZEB1 in PANC-1 cells(P＜0.05),inhibit the expression of miR-429,and exhibit concentration dependence.Overexpression of miR-429 could significantly suppress the expression of cell surface molecule PD-L1 induced by HG in PANC-1 cells,while overexpression of ZEB1 could reverse the inhibitory effect of miR-429 over-expression on the expression of cell surface molecule PD-L1 induced by HG.After establishing a co-culture system with CD8+T cells,compared with the control group,the proliferation activity of PANC-1 cells in the HG group sig-nificantly increased,and the apoptosis rate and cytotoxicity significantly decreased(P＜0.05).Compared with the HG+mimics NC group,the proliferation activity of PANC-1 cells in the HG+mimics group significantly decreased,and the apoptosis level and cytotoxicity significantly increased(P＜0.05).Compared with the HG+mimics group,the proliferation activity of PANC-1 cells in the HG+mimics+oe-ZEB1 group significantly increased,and the apop-tosis rate and cytotoxicity significantly decreased(P＜0.05).Dual luciferase reporter gene assay confirmed that miR-429 negatively regulated ZEB1.Conclusion High glucose promotes immune escape of PANC-1 cells by down-regulating the expression level of miR-429,negatively regulating the expression of ZEB1 mRNA,and increasing the expression level of cell surface molecule PD-L1 in PANC-1 cells.

Objective:To understand the prevalence of chronic kidney disease (CKD) in adults in Qingdao.Methods:A multi-stage stratified random sampling method was used to select 6 240 local residents aged ≥18 years in Qingdao as study subjects from May 2019 to September 2020, the demographic data of the study subjects were collected by face-to-face survey method. The prevalence of CKD in adults in Qingdao were analyzed using software SPSS 25.0.Results:A total of 5 996 adults in Qingdao were included in this study. The overall prevalence rate of CKD in the adults was 8.22%. The prevalence rates of CKD in men and women were 7.70% and 8.74%, respectively. The prevalence rate of CKD was 10.28% in urban residents and 7.25% in rural residents, the differences in the prevalence of CKD among different age, educational level and marital status groups were significant ( P<0.001). The prevalence of CKD tended to increase with age and decrease with the increase of education level. Conclusions:The prevalence of CKD in adults of Qingdao was relatively high. It is necessary to actively carry out the early prevention and treatment of CKD and strengthen the screening and prevention of CKD to reduce the incidence and slow development of CKD.

OBJECTIVE To explore the effect of silencing RNA-373(mir-373)on the proliferation and apoptosis of laryngeal cancer cells and its mechanism.METHODS Laryngeal cancer cells were divided into control group,overexpression group and silence group.Stable overexpression group and silence group were established by cell transfection.MTT assay was used to detect cell proliferation,TUNEL method was used to detect the apoptotic ability,cell invasion was detected by Transwell chamber,cell migration was detected by cell scratch test,Western blot was used to detect the expression of β-Catenin,c-myc,CyclinD1,MMP-9,bc1-2 and Bax in Wnt/β-catenin signaling pathway.RESULTS Compared with over expression group,the expression of mir-373 in silence group was significantly decreased(t=15.062,P<0.05).Compared with the overexpression group,the apoptosis rate was higher and the proliferation rate was lower in the silencing group at different time points(t=31.025,16.453,22.475,29.672,P<0.05).Compared with overexpression group,the invasion ability and migration number of cells in silencing group were lower(t=35.254,37.205,P<0.05).Compared with overexpression group,the expression levels of β-Catenin,c-myc,CyclinD1,MMP-9,bc1-2 protein in silencing group were lower,and Bax protein was higher(t=4.218,5.307,4.609,5.005,4.328,3.984,P<0.05).CONCLUSION Silencing mir-373 may promote apoptosis and inhibit invasion,proliferation and migration of laryngeal cancer cells by promoting Bax expression,inhibiting the expression of β-Catenin,c-myc,CyclinD1,MMP-9 and bc1-2,and blocking Wnt/β-catenin signaling pathway.

Objective To investigate the determinants of linezolid-associated neurological adverse reactions in patients with multidrug-resistant tuberculosis and develop a risk prediction model for such adverse events.Methods A prospective cohort study design was employed to select 120 patients with drug-resistant pulmonary tuberculosis who received a chemotherapy regimen containing linezolid at Guangzhou Chest Hospital from April 2023 to January 2024 as the study population.Clinical data,adverse reactions,and plasma concentration of linezolid were collected during fasting and at 2 hours post-medication.Univariate analysis and multivariate logistic regression were conducted to identify factors influencing linezolid-related neurological adverse reactions.Furthermore,a prediction model for such adverse reactions was developed,and its predictive efficacy and calibration ability were evaluated using ROC analysis.Results Re-treatment(OR=2.540,P=0.028),coexistence of cavities(OR=4.092,P=0.021),anemia(OR=10.921,P=0.005),and Cmin≥0.7665 mg/L(OR=6.813,P<0.001)are independent risk factors for the occurrence of linezolid-related neurological adverse reactions.The prediction model,based on these four factors,exhibits an AUC of 0.851(95%CI:0.774～0.929),accompanied by a Youden index of 0.590,a sensi-tivity of 66.7%,and a specificity of 92.3%.Moreover,the prediction model demonstrates excellent calibration ability.(Hosmer-lemeshow χ2=8.719,P=0.273).Conclusion In MDR/RR-TB patients,the presence of cavita-tion,retreatment,and anemia may confer a heightened risk of linezolid-related neurological adverse reactions.A risk prediction model incorporating these four indicators demonstrates significant predictive value for the occurrence of such adverse events.