Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.

OBJECTIVE To explore the effect of Shilinqing granules on calcium oxalate nephrolithiasis in rats and its potential mechanisms through the silence information regulator 1 （SIRT1）/nuclear factor-κB （NF-κB）/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Sixty male SD rats were randomly assigned to control group， model group， and low- ， medium- ， high-dose groups of Shilinqing granules （6.5， 13， 26 g/kg， calculated based on crude drug）， and high-dose of Shilinqing granules+inhibitor group （Shilinqing granules 26 g/kg+SIRT1 inhibitor nicotinamide 5 mg/kg）， with 10 rats in each group. Except for the control group， the remaining groups of rats were given 1% ethylene glycol solution to drink freely and were intubated with 2% ammonium chloride solution 2 mL （once a day， for 4 weeks） to construct a calcium oxalate nephrolithiasis model. At the same time of modeling， the administration groups were intubated or （and） intraperitoneally injected with the corresponding drug solutions， while the control and the model groups were intubated with physiological saline and intraperitoneally injected with dimethyl sulfoxide. The body weight， kidney index， urine/ blood biochemical indicators [24-hour urine volume， urine pH， urinary calcium ion （Ca2+） and urinary oxalic acid （Ox） content， as well as blood creatinine （Scr）， blood urea nitrogen （BUN）， blood Ca2+ content]， serum inflammatory indicators [levels of interleukin-1β （IL-1β）， IL-18]， pathological changes in renal tissue， calcium oxalate crystallization， and crystal scoring were observed. The protein expressions of SIRT1， NLRP3， and NF-κB in renal tissue were detected. RESULTS Compared with the control group， the model group had severe renal tissue damage and a large number of calcium oxalate crystals， with significant decrease or downregulation in body weight， 24-hour urine volume， urine pH， and protein expression of SIRT1 in renal tissue （P＜ 0.05）； crystal score， kidney index， urinary contents of Ca2+ and Ox， serum contents of Scr， BUN and Ca2+， and serum levels of IL- 1β and IL-18， as well as the protein expressions of NF-κB， NLRP3 in renal tissue were significantly increased or upregulated （P＜0.05）. The pathological changes in the rats of 2024ZY2045） each dose group of Shilinqing granules were improved， the calcium oxalate crystals were reduced， and all quantitative indicators were significantly improved as compared with the model group （P＜0.05）； while the SIRT1 inhibitor could significantly reverse the improving effects of high-dose of Shilinqing granules on the above indicators （P＜0.05）. CONCLUSIONS Shilinqing granules can inhibit the formation of calcium oxalate nephrolithiasis in rats， reduce the levels of inflammatory indicators and its mechanism may be related to upregulating protein expression of SIRT1， and downregulating protein expressions of NF-κB and NLRP3.

The most prevalent kind of renal calculi,calcium oxalate(CaOx),is characterized by its propensi-ty for recurrence in the urinary system.The development of CaOx renal calculi is greatly affected by macrophage polariza-tion.Particular oxalate causes an imbalance in macrophage polarization,which skews the M1/M2 ratio and makes it easier for CaOx crystals to accumulate in the kidneys and grow into calcium plaques in the renal papilla.Notably,M2 macro-phages can prevent CaOx renal calculi by consuming crystals and reducing inflammatory stress.As a result,immunothera-peutic techniques that alter M1 and M2 macrophage polarization are extremely promising for preventing CaOx renal calcu-li.To clarify the respective roles of M1 and M2 macrophages in the formation of CaOx crystals and provide insights for de-veloping immunotherapeutic interventions against CaOx renal calculi,this review summarizes the mechanisms underlying macrophage polarization in the genesis of CaOx renal calculi.

Objective To screen the distribution frequency of Mur blood group among voluntary blood donors in Hezhou,Guangxi,and further analyze the molecular basis of of Mur antigen positive samples.Methods The Mur pheno-type of voluntary blood donors in Hezhou was serologically screened using microplate method,and the distribution frequency of Mur antigens in different ethnic groups was analyzed.Genetic typing was performed on these positive samples with PCR-SSP method to verify the accuracy of the serological method,and the genetic background was sequenced and analyzed.Re-sults Among 3 298 samples from voluntary blood donors in Hezhou,432(13.10%,432/3 298)were screened positive for Mur antigen,and PCR-SSP genotyping validation showed that all 432 samples were electrophoretic positive.Among them,the proportion of Han blood donors with positive Mur antigen was12.79%(331/2 587),Yao ethnic group was13.25%(64/483),Zhuang ethnic group was 16.51%(36/218),and no statistically significant difference was found in the three groups(P＞0.05).Further sequencing results showed that 428 samples were GYP(B-A-B)Mur,also known as GYP.Mur type(12.98%,428/3 298),the other 4 samples were GYP(B-A-B)Bun,also known as GYP.Bun type(0.12%,4/3 298).Conclusion The Mur blood type frequency is high in the voluntary blood donors in Hezhou,Guangxi,and is predominant characterized by GYP.Mur genotype.Due to ethnic integration,no significant difference was noticed in the frequency of Mur blood type distribution between Han,Zhuang and Yao population.Therefore,conducting extensive Mur blood group antigen and antibody testing in Hezhou is of great significance for ensuring clinical blood transfusion safety.

Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamy-cin(mTOR)signaling pathway is an important regulating pathway for metabolism,proliferation and survival in cells,and plays a pivotal role in maintaining cellular homeostasis.This signaling pathway participates in the occurrence and development process of multiple diseases by mediating the cellular autophagy,such as tumors,neurodegenerative disorders(ND)and metabolic diseases.This paper reviews the role of PI3K/Akt/mTOR signaling pathway in autophagy regulation in order to better understand the regulatory mechanisms of cellular metabolism and survival,moreover investigate the role of this signal pathway in multiple diseases and direc-tion of the future study to provide reference for explore the new disease treatment methods.

Objective:To establish ultra performance liquid chromatography (UPLC) characteristic chromatogram of Pulsatilla chinensis; To provide reference for the origin identification and quality control of Pulsatilla chinensis. Methods:UPLC Method was adopted. The determination was performed on a column of Agilent SB C18 (2.1 mm×100 mm, 1.8 μm) . The mobile phase was acetonitrile-methanol (2:1) -0.1% phosphoric acid solution by fradient elution at a flow rate of 0.30ml/min. The column temperature was 30 ℃. The detection wavelength was 215 nm. The injection volume was 2 μl. The common counterfeit products and medicinal herbs of Pulsatilla chinensis from different areas were evaluated by comparison of characteristic chromatogram, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Results:There were 9 characteristic peaks in the characteristic chromatogram of Pulsatilla chinensis, and 8 common peaks were identified by high resolution mass spectrometry and comparison of reference materials. Through PCA analysis, it was possible to clearly distinguish the medicinal herbs of Pulsatilla chinensis from different areas. Combined with OPLS-DA analysis, it was found that peak 2, peak 3, peak 6 were the main markers of Pulsatilla chinensis from different producing areas. Conclusion:The established method has good specificity, repeatability and durability, and it can effectively distinguish the common counterfeits of Pulsatilla chinensis, and provide the basis of quality control and selection of origin for Pulsatilla chinensis.

Objective:To establish the ultra high performance liquid chromatography (UPLC) fingerprints of Mume flos at different flowering stages; To provide reference for the quality research of Mume flos.Methods:The fingerprints of Mume flos were established by UPLC method, and the common peaks were identified by high performance liquid chromatography high resolution mass spectrometry (LC-MS). Chemometrics analysis was carried out with the fingerprints' common peak area of plum blossom at different flowering stages as a variable. Semiquantitative analysis of changes in flavonoids and phenolic acids in Mume flos at different flowering stages was conduct using peak area calculation method.Results:Totally 31 common peaks were identified in the fingerprints of plum blossom medicinal materials at different flowering stages and 9 components were identified. Clustering analysis (HCA) and principal component analysis (PCA) both classified plum blossom medicinal herbs at different flowering stages into three categories. Among them, there were significant differences between the groups at the bud stage, blooming period, and final flowering period, while the differences between the groups at blooming period and final flowering period were relatively small. The orthogonal partial least squares discriminant analysis (OPLS-DA) screened 16 different components with VIP>1.0. The contents of phenolic acids in different flowering stages were as follows: bud stage>blooming period>final flowering period, while the contents of flavonoids were as follows: blooming period>final flowering period>bud stage.Conclusions:This method is simple and reliable, and can provide reference for the quality evaluation of plum blossom medicinal materials at different flowering stages.

Objective To establish the ultra-high performance liquid chromatography(UPLC)chromatographic fingerprint of Notopterygii Rhizoma et Radix;To determine the contents of ferulic acid,nodakenin,ammijin,notopterol,isoimperatorin and volatile oil of Notopterygii Rhizoma et Radix from different producing areas;To provide reference for quality evaluation of Notopterygii Rhizoma et Radix.Methods Waters BEH C18 chromatographic column(2.1 mm×150 mm,1.7 μm)was used,with mobile phase acetonitrile-0.02%formic acid aqueous solution gradient elution,flow rate 0.25 mL/min,column temperature 25℃,detection wavelength 330 nm,injection volume 2 μL.UPLC fingerprints of 25 batches of Notopterygii Rhizoma et Radix were established,and the similarity analysis and chemometrics analysis were carried out.The contents of ferulic acid,nodakenin,ammijin,notopterol and isoimperatorin were determined simultaneously,and the contents of volatile oil was determined by steam distillation method.Results Totally 23 common fingerprint peaks were calibrated,11 known components were identified.According to the results of the cluster analysis and principal component analysis,25 batches of Notopterygii Rhizoma et Radix samples were divided into 3 categories,and the 6 potential differential components were screened out by orthogonal partial least squares-discriminant analysis(OPLS-DA).The results showed that the contents of notopterol and volatile oil from Sichuan Province were higher than those from Gansu Province and Qinghai Province.Conclusion The method established in the study is accurate and reliable,which can provide scientific basis and reference for the quality evaluation and control of Notopterygii Rhizoma et Radix.

OBJECTIVE To investigate the mechanism of Shilinqing granules preventing the formation of calcium oxalate kidney stones in rats. METHODS Sixty rats were randomly divided into blank group， model group， Shilingqing granules low- dose， medium-dose and high-dose groups （6.5， 13， 26 g/kg）， SIRT3 inhibitor group （Shilingqing granules 26 g/kg+SIRT3 inhibitor 25 mg/kg）， with 10 rats in each group. Except for blank group， other groups were given 1% ethylene glycol solution instead of drinking water， and intragastrical administration of 2% ammonium chloride solution 2 mL， for 4 consecutive weeks， to induce kidney stones rat model； at the same time， administration groups were given relevant medicine intrgastrically， blank group and model group were given constant volume of normal saline intrgastrically. The 24 h urine volume， urine pH， urine contents of Ca2+ and oxalic acid （Ox）， serum contents of creatinine （Cr）， blood urea nitrogen （BUN） and Ca2+ were all determined； the renal histopathology， calcium oxalate crystallization and ultrastructure were observed； the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， reactive oxygen species （ROS） and osteopontin （OPN） in renal tissue of rats were determined； mRNA and protein expressions of SIRT3， FOXO3a， and SOD2 in renal tissue of rats were determined. RESULTS Compared with blank group， 24 h urine volume， urine pH， SOD level， mRNA and protein expressions of SIRT3， FOXO3a and SOD2 in renal tissue were decreased significantly in model group （P＜0.05 or P＜0.01）. The contents of urine Ca2+ and Ox， serum contents of Cr， BUN and Ca2+ and the levels of ROS， MDA and OPN in renal tissue were increased significantly （P＜0.01）. The pathological damage of renal tissue was severe， with a large number of diffuse black crystals， thickened glomerular basement membrane， and mitochondrial edema in podocytes and renal tubular epithelial cells. Compared with model group， the above indexes （except for serum content of Ca2+ in low-dose group） were significantly reversed in Shilinqing granules groups （P＜0.05 or P＜0.01）； pathological renal damage， calcium crystal， mitochondrial damage of glomerular podocyte and renal tubular epithelial cell were significantly improved； there was no statistical significance in the changes of above indexes in SIRT3 inhibitor group （P＞0.05）. CONCLUSIONS Shilinqing granules can effectively inhibit the formation of calcium oxalate kidney stones in rats and improve renal damage， the mechanism of which may be related to the improvement of anti-oxidant effect and the activation of SIRT3/FOXO3a signaling pathway.

OBJECTIVES: Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. METHODS: Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. RESULTS: A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). CONCLUSIONS Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.
Humans ; Citric Acid/adverse effects* ; Prospective Studies ; Sodium Citrate ; Hemorrhage/chemically induced* ; Citrates/adverse effects* ; Anticoagulants/adverse effects* ; Renal Dialysis/adverse effects*