ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form"， this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells （BMSCs） by mediating peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and peroxisome proliferators-activated receptor γ （PPARγ）， providing theoretical support for the prevention and treatment of postmenopausal osteoporosis （PMOP） using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group， Zuogui Wan （ZGW） group， Yougui Wan （YGW） group， and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide （MTT） method， and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ， CCAAT/enharcer-binding protein （C/EBP）α， C/EBPβ， lipoprotein lipase （LPL） protein， brown adipose tissue-related （BAT） proteins PGC-1α， uncoupcing protein 1 （UCP1）， PR domdin-containing protein 16 （PRDM16）， mitochondrial biogenesis-related PGC-1α， nuclear respiratory factor 1 （Nrf1）， nuclear factor E₂-related factor 2 （Nrf2）， and mitochondrial transcription factor A （TFAM）. The expression of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， LPL genes， and the copy number of cytochrome B （CytoB mtDNA） gene was detected using real-time polymerase chain reaction （Real-time PCR）. Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group， the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed， and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， and LPL were significantly downregulated （P<0.01）， while those of the BAT-related factors PGC-1α， UCP1， PRDM16 were significantly upregulated （P<0.01）. The number of mitochondria increased， accompanied by reduced swelling. The double membrane and cristae structure were clear， and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased （P<0.01）. The protein expression levels of mitochondrial biogenesis-related PGC-1α， Nrf1， Nrf2， and TFAM in each treatment group were significantly increased （P<0.01）. ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.

Objective: To explore the mechanism of Buzhong Yiqi Decoction in modulating macrophage polarization and intervening in autoimmune thyroiditis (AIT) mice. Methods: Using the random number table method, 48 SPF-grade NOD.H-2h4 mice were assigned to the normal, model, low-dose (4.10 g/kg), medium-dose (8.19 g/kg), high-dose group (16.38 g/kg) of Buzhong Yiqi Decoction, and selenium yeast tablet (0.026 mg/kg) groups, with eight mice in each group. All groups, except the normal group, were free to drink high iodine water (0.05% sodium iodide) to prepare AIT mouse models for 8 consecutive weeks. After the modeling was complete, each treatment group was orally administered with the corresponding medication, while the normal and model groups were orally administered with an equal volume of distilled water once a day for 8 consecutive weeks. High-performance liquid chromatography with an oscillometric refractive detector was used to analyze the content of Astragaloside Ⅳ in Buzhong Yiqi Decoction. Hematoxylin and eosin staining was used to observe the pathological morphology of mouse thyroid tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α). An immunofluorescence assay was used to detect the positive area percentage of M1 and M2 macrophages in mouse thyroid tissue. Flow cytometry assay was used to detect macrophage polarization in mouse spleen tissue. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), nuclear factor kappa B inhibitory protein α (IκBα), and nuclear factor-κB (NF-κB) p65 in mouse spleen tissue. Western blotting was used to detect the expression of the phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), and NLRP3 protein in mouse spleen tissue. Results: The content of Astragaloside Ⅳ in Buzhong Yiqi Decoction was (7.09±0.06) g/L. Compared to the normal group, significant lymphocyte infiltration was observed in the thyroid tissue of mice in the model group. The levels of serum TPO-Ab, TgAb, IL-6, and TNF-α increased (P<0.05). The positive area percentage of M1 macrophages in thyroid tissue increased (P<0.05). The proportion of M1 macrophages and M1/M2 in spleen tissue increased (P<0.05). The relative expression levels of NF-κB p65 and NLRP3 mRNA in spleen tissue increased (P<0.05). The relative expression of p-IκBα, p-NF-κB p65, and NLRP3 proteins increased (P<0.05). Compared to the model group, the inflammation infiltration degree in the thyroid tissue of mice in each dose group of Buzhong Yiqi Decoction and selenium yeast tablet group was reduced, the serum TPO-Ab, TgAb, IL-6, TNF-α content was decreased, the spleen tissue M1/M2 was reduced, the expression of NF-κB p65 mRNA was reduced, and the relative expression levels of p-IκBα, p-NF-κB p65 protein were reduced (P<0.05). The Buzhong Yiqi Decoction high-dose and selenium yeast tablets groups showed an increase in IL-10 content, an increase in positive area percentage of M2 macrophages in thyroid tissue, an increase in M2 macrophages proportion in spleen tissue, and a decrease in NLRP3 mRNA and protein relative expression levels (P<0.05). Conclusion Buzhong Yiqi Decoction may regulate macrophage polarization by inhibiting the NF-κB/NLRP3 signaling pathway, thus improving the inflammatory damage in mice with AIT.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

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With the improvement of surgical techniques and deeper anatomical understanding, the concept of precision surgery has gradually developed. The necessity of traditional extensive organ resection for the treatment of benign and borderline tumors is being challenged due to the high risk of long-term complications. Over the past 40 years, various modified surgical techniques have emerged, with duodenum-preserving pancreatic head resection as a representative procedure. The surgical indications have gradually transitioned from chronic pancreatitis to benign and borderline tumors of the pancreatic head. The extent of resection has evolved from major partial resection and subtotal resection to total resection of the pancreatic head. The surgical approach has also progressed from traditional open surgery to minimally invasive techniques such as laparoscopic or robot-assisted surgery, reflecting updates and optimizations in treatment concepts and surgical methods. This paper discusses the development, surgical indications, and related complications of duodenum-preserving pancreatic head resection. The aim is to provide a reference for the more standardized and rational selection of this surgical procedure in clinical practice while reducing the incidence of complications.

Objective To explore the effect of pristimerin combined with cisplatin on proliferation and apoptosis of nasopharyngeal carcinoma cells.Methods CCK-8 assay was used to examine the survival rate of HNE-1 and CNE-2Z cells following treatment for 24 h with different concentrations of pristimerin,cisplatin or their combination.The changes in colony formation ability,apoptosis,and intracellular reactive oxygen species(ROS)levels of the treated cells were analyzed using colony formation assay and flow cytometry.Western blotting was performed to detect the changes in protein expressions in the cells.The effects of pre-treatment with NAC on proliferation,apoptosis,and PI3K/AKT signaling pathway were observed in pristimerin-and/or cisplatin-treated cells.Results Both pristimerin and cisplatin significantly lowered the survival rate of HNE-1 and CNE-2Z cells(P<0.05).Compared with pristimerin or cisplatin alone,their combination more strongly inhibited survival and colony formation ability of the cells,increased cell apoptosis rate and intracellular ROS levels,upregulated the protein expressions of Bax,cleaved caspase-3,and cleaved PARP,and downregulated the protein expressions of Bcl-2,Mcl-1,PARP and p-PI3K and p-AKT(P<0.05).NAC pretreatment significantly attenuated proliferation inhibition and apoptosis-promoting effects of pristimerin combined with cisplatin,and partially restored the downregulated protein expressions of p-PI3K and p-AKT in HNE-1 and CNE-2Z cells with the combined treatment(P<0.05).Conclusion Pristimerin can enhance cisplatin-induced proliferation inhibition and apoptosis in nasopharyngeal carcinoma cells,the mechanism of which may involve ROS-mediated deactivation of the PI3K/AKT signaling pathway.

With the improvement of surgical techniques and deeper anatomical understanding, the concept of precision surgery has gradually developed. The necessity of traditional extensive organ resection for the treatment of benign and borderline tumors is being challenged due to the high risk of long-term complications. Over the past 40 years, various modified surgical techniques have emerged, with duodenum-preserving pancreatic head resection as a representative procedure. The surgical indications have gradually transitioned from chronic pancreatitis to benign and borderline tumors of the pancreatic head. The extent of resection has evolved from major partial resection and subtotal resection to total resection of the pancreatic head. The surgical approach has also progressed from traditional open surgery to minimally invasive techniques such as laparoscopic or robot-assisted surgery, reflecting updates and optimizations in treatment concepts and surgical methods. This paper discusses the development, surgical indications, and related complications of duodenum-preserving pancreatic head resection. The aim is to provide a reference for the more standardized and rational selection of this surgical procedure in clinical practice while reducing the incidence of complications.

Objective:To summarize the clinical and pathological characteristics, treatment methods, and prognosis of papillary renal neoplasm with reverse polarity (PRNRP).Methods:The clinical and pathological data of six pathologically confirmed PRNRP patients admitted to Renji Hospital affiliated with Shanghai Jiaotong University School of Medicine from August 2022 to August 2023 were retrospectively analyzed. Among them, three were male and three were female, with an average age of (55.3±10.5) years old. All six cases were incidentally discovered during health examinations. Preoperative contrast-enhanced CT scans showed tumors with cortical phase manifestations of uneven enhancement, avascularity, and indistinct borders, with CT values of (85.6±18.7) HU. In the corticomedullary phase, the CT values showed mild elevation, with an average of (94.3±4.7) HU. In the delayed phase, the tumor boundaries were clear, and the enhancement degree was significantly lower than that of the surrounding renal cortex and medulla, with a tumor CT value of (86.3±11.9) HU. The pseudocapsule of the tumor was not clearly displayed on contrast-enhanced CT scans. All cases underwent partial nephrectomy, including two cases of robot-assisted laparoscopic partial nephrectomy and four cases of laparoscopic partial nephrectomy.Results:Postoperative pathological measurements revealed a maximum tumor diameter ranging from 6 to 15 mm, with an average diameter of (11.0±3.5) mm. All six cases were classified as pT 1aN 0M 0 stage. Microscopically, the tumors exhibited branching papillary structures with eosinophilic cytoplasm, and the tumor cells displayed low-grade nuclei located at the top of the cytoplasm and away from the basal membrane. Immunohistochemical analysis showed diffuse strong positivity for GATA3 and CK7, while CA-Ⅸ expression was negative. The median follow-up time after surgery was 10(9, 13) months, and no tumor recurrence or metastasis was observed. Conclusions:PRNRP is a rare, low-grade malignant papillary renal tumor. Contrast-enhanced CT scan has characteristic features of avascularity. Pathological morphological features are low-grade nuclei located at the top of the cytoplasm and far away from the basal membrane, forming a "reverse polarity". The immunophenotype shows positive expression of GATA3 and CK7. Partial nephrectomy is the recommended treatment approach, and the postoperative prognosis is favorable.

Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.