ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Acute cerebral infarction(ACI)has the characteristics of onset nasty and high mortality,and thus the rapid determination of the occurrence and development of ACI plays a key role in the diagnosis,treatment and prognosis of ACI patients.It has shown that the serum level of human haptoglobin(Hp)is related to ACI.In this study,surface enhanced Raman scattering(SERS)combined with immune recognition was applied to establish a quantitative analysis method for serum Hp.Firstly,the SERS substrate of silver nanoparticles was prepared on silicon wafer,and 4-mercaptobenzoic Acid(MBA)was used as a Raman probe by forming Ag—S bond and connecting it on the surface of nanoparticles.The carboxyl group of MBA was linked to amino group of self-made high-affinity antibody through forming CO—NH structure thus forming a SERS self-assembled chip of Hp(Ag/MBA/anti-Hp).Hp in serum could be specifically captured by antibodies on SERS substrate,which caused the shift of SERS characteristic peak of MBA.The results showed that there was a good linear relationship between the logarithm of Hp concentration and the SERS characteristic peak shift of MBA.The detection range was 1-1000 ng/mL(R2=0.988).The Hp concentrations in serum of 90 ACI patients were determined by this method,and the results were consistent with those of ELISA method,which proved the practicability and accuracy of this method.This method was highly specific,simple and convenient,which could realize the specific recognition and quantitative analysis of serum Hp,so as to be an effective means for clinical detection of serum Hp,thus providing a reference for the treatment and prognosis of ACI.

Objective To observe the inhibitory effect of Guiqi Yiyuan ointment on tumor growth in mice with Lewis lung cancer,and to explore the molecular mechanism of Guiqi Yiyuan ointment combined with cisplatin through phosphoinositide 3-kinase/protein kinase B/mammalian rapamycin target protein(PI3K/Akt/mTOR)signal pathway.Methods Sixty C57BL/6 mice were randomly divided into 6 groups with 10 mice in each group.Except for the blank group(0.9％NaCl),Lewis lung cancer-bearing mice were randomly divided into model group(0.9％NaCl),control group(0.9％NaCl,cisplatin 5 mg·kg-1)and low,medium,high dose experimental groups(Guiqi Yiyuan ointment 1.6,3.3,6.6 g·kg-1,cisplatin 5 mg·kg-1).Flow cytometry was used to detect bone marrow-derived suppressor cells(MDSCs);the expression of related proteins in tumor tissues was detected by Western blot.Results The tumor inhibition rates in control group and low,medium,high dose experimental groups were(39.87±4.45)％,(45.74±14.97)％,(57.78±4.70)％and(69.82±11.05)％.The proportion of MDSCs in bone marrow of in blank group,model group,control group and low,medium,high dose experimental groups were(36.13±1.08)％,(68.63±2.94)％,(58.93±2.02)％,(58.00±1.50)％,(50.93±5.06)％and(43.07±2.41)％.The protein expressions of p-PI3K/PI3K in model group,control group and low,medium and high experimental groups were 0.97±0.03,0.77±0.02,0.72±0.01,0.68±0.03 and 0.53±0.02;PTEN were 0.21±0.07,0.65±0.07,0.74±0.06,0.99±0.13,1.11±0.13;p-Akt/Akt were 1.01±0.02,0.82±0.02,0.77±0.00,0.72±0.03 and 0.52±0.04;p-mTOR/mTOR were 1.01±0.01,0.76±0.05,0.69±0.07,0.59±0.06 and 0.47±0.06.There were significant differences between low,medium,high experimental groups and control group(all P＜0.05).Conclusion Guiqi Yiyuan ointment combined with cisplatin can significantly improve the quality of life and inhibit tumor growth in mice.The mechanism may be the inhibition of PI3K/Akt/mTOR signal pathway and the enhancement of tumor cell apoptosis and autophagy.

Objective To observe the effects of traditional Chinese medicine compound Platycodon grandiflorum Bai powder on the growth of subcutaneously implanted tumor and the expression of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),cysteinyl aspartate specific proteinase(caspase)-3 and caspase-9 in subcutaneously implanted tumor of Lewis lung cancer mice.Methods The model of transplanted tumor of Lewis lung cancer in mice was established.Seventy SPF male C57BL/6 mice were randomly divided into blank group,model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combined group.Blank group and model group were given 0.9％NaCl 0.2 mL by gavage;control group was given 0.9％NaCl by gavage and 25 mg·kg-1cisplatin intraperitoneally;high,medium,low dose experimental groups were given 193,96,48 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,respectively;combined group was given 96 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,and 25 mg·kg-1 cisplatin intraperitoneally,once every other day.The myelogenous suppressor cells(MDSCs)of mouse bone marrow were detected by flow cytometry,and the expressions of Bel-2,Bax,caspase-3 and caspase-9 in tumor cells were detected by immunofluorescence.Results The percentage of MDSCs in bone marrow of mice in blank group,model group,low dose experimental,medium,high dose experimental group,control group and combination group were(32.50±2.76)％,(63.13±3.14)％,(48.43±2.23)％,(42.53±1.28)％,(32.93±3.56)％,(51.30±4.25)％and(19.90±6.21)％,respectively.The fluorescence intensities of Bax in model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combination group were 10.42±0.68,12.40±1.23,15.14±0.65,22.95±1.76,27.18±1.62 and 31.61±1.28;Bel-2 were 36.85±0.80,33.92±4.20,28.88±1.01,20.04±2.21,15.69±2.36 and 6.05±0.73;caspase-3 were 5.28±0.44,7.63±0.55,9.66±0.85,14.73±1.18,17.95±1.29 and 22.92±1.95;caspase-9 were 9.48±0.90,11.57±0.72,13.45±0.93,15.73±1.44,19.20±0.96 and 23.21±1.51.There were significant differences between medium,high dose experimental groups and model group(all P＜0.05),and there were significant differences between combined group and control group(all P＜0.05).Conclusion Platycodon grandiflorum Bai powder can up-regulating the expression of Bax,caspase-3 and caspase-9,down-regulating the expression of Bel-2,inhibiting MDSCs,promoting tumor cell apoptosis and inhibiting tumor growth.

Objective To investigate the formation and mechanism of dipeptidylpeptidase-4 inhibitor anagliptin inhibiting lung metastasis of colorectal cancer.Methods Twenty-four male BALB/c mice were randomly divided into normal group,model group,anagliptin group.The control group did not undergo any treatment.The model group was injected with 0.1 ml CT-26 cells of 109 cells/L.once through the tail vein of the mouse to construct a lung metastasis model,while the anagliptin group was injected intraperitoneally 20 mg/(kg d)0 day after constructing a lung metastasis model.The mice were sacrificed after 14 days.HE staining was used to detect the morphological alteration.Determination of CT-26 cell viability through MTT assay and CT-26 cell apoptosis was detected by flow cytometry and live/dead cell staining.Reactive oxygen species(ROS)production was measured by ROS kit.Western blotting was conducted to measure the expression level of Bcl-2,Bax,cleaved-caspase-3,superoxide dismutase(SOD-1)and SOD-2.Results HE staining showed that the administration of anagliptin could significantly inhibit the abnormal changes in the model group.Anagliptin inhibited the viability of CT-26 cells above 2 mmol/L.Anagliptin promoted the apoptosis of CT-26 cells.Incubation of anagliptin in CT-26 cells significant promoted the production of ROS.Incubation of anagliptin stimulated the expressions of Bax and cleaved-Caspase-3,while down-regulated the expression of Bcl-2 in CT-26 cells.Administration of anagliptin decreased the expression of SOD-1,but not SOD-2.Conclusion Anagliptin promotes apoptosis of colorectal cancer cells and inhibits the formation of lung metastatic tumors through the SOD-1/ROS pathway.

Objective To compare clinical efficacy of robot-assisted(RA)and remote sensing navigation alignment(RSNA)system-assisted total knee arthroplasty(TKA).Methods From March 2023 to June 2023,60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis(KOA)were admitted and divided into RSNA group and RA group according to different treatment methods,with 30 patients in each group.There were 5 males and 25 females in RSNA group,aged from 56 to 81 years old with an average of(66.33±7.16)years old;body mass index(BM1)ranged from 19.87 to 38.54 kg·m-2 with an average of(28.40±6.18)kg·m-2;the courses of disease ranged from 5 to 36 months with an average of(18.20±8.98)months;RSNA system was used to assist the positioning of osteotomy.There were 7 males and 23 females in RA group,aged from 55 to 82 years old with an average of(67.83±8.61)years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an aver-age of(28.01±4.89)kg·m-2;the courses of disease ranged from 3 to 33 months with an average of(17.93±9.20)months;RA was performed.Operation time,incision length,latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups.Hip-knee ankle angle(HKAA),HKAA deviation,lateral distal femoral angle(LDFA),medial proximal tibial angle(MPTA)and posterior tibial slope(PTS)were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index(WOMAC)and Knee Society score(KSS)were used to evaluate functional recovery before operation,3 and 6 months after operation.Results The operation was performed successfully in both groups,and there were no serious complications such as vascular and nerve injury during operation.The wound healed well at stage Ⅰafter operation,and the follow-up time was 6 months.The operation time,latent blood loss at 2 weeks after operation and inci-sion length in RSNA group were(94.35±5.75)min,(130.54±17.53)mland(14.73±2.14)cm,respectively;while(102.57±6.88)min,(146.33±19.47)ml and(16.78±2.32)cm in RA group,respectively.RSNA group was better than RA group(P＜0.05).No deep vein thrombosis occurred in both groups at 2 weeks after operation,5 patients occurred intermuscular vein throm-bosisin in RSNA group and 8 patients in RA group,the difference was not statistically significant(P＞0.05).In RSNA group,HKAA,LDFA and MPTA were(173.00±5.54)°,(86.96±3.45)°,(82.79±3.35)° before operation,and(178.34±1.85)°,(89.92±0.42)°,(89.84±0.73)° at 1 week after operation,respectively.In RA group,HKAA,LDFA and MPTA were(173.31±6.48)°,(87.15±3.40)° and(82.99±3.05)° before operation,and(178.52±1.79)°,(90.03±0.39)° and(90.15±0.47)° at 1 week after operation,respectively.HKAA,LDFA and MPTA were significantly improved in both groups at 1 week after oper-ation(P＜0.05).There were no significant difference in HKAA,LDFA,MPTA and PTS between two groups before operation and 1 week after operation(P＞0.05).There was no significant difference in deviation distribution of HKAA at 1 week after op-eration(x2=2.61 1,P=0.456).There were no significant difference in WOMAC and KSS between two groups before operation,3 and 6 months after operation(P＞0.05),and postoperative WOMAC and KSS at 3 and 6 months between two groups were im-proved compared with those before operation(P＜0.05).Conclusion Both RA and RSNA system assisted TKA could obtain ac-curate osteotomy,RA has higher surgical accuracy,RSNA system assisted operation has less trauma,and operation is simpler.