Objective: To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome. Methods: Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared. Results: There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05). Conclusion The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

To investigate the impact and underlying mechanism of NOP2/Sun RNA methyltransferase 2 (NSUN2) on gastric cancer progression, TCGA database was used and revealed a significant upregulation of NSUN2 expression in gastric cancer tissues. Western blot analysis revealed that NSUN2 was upregulated in gastric cancer cells compared with gastric mucosal epithelial cells. Colony formation assays demonstrated an enhanced colony-forming capacity in NSUN2-overexpressing cells. Furthermore, Transwell assays showed a marked increase in cell migration and invasion upon high NSUN2 expression. Moreover, TCGA database analysis suggested ARMC9 as a potential downstream target of NSUN2. Subsequently, MeRIP-qPCR analysis revealed that NSUN2 overexpression could increase m5C modification of ARMC9 mRNA, and reduce its degradation rate, thus enhancing protein expression. Additionally, ARMC9 overexpression augmented cellular colony formation and migratory and invasive capabilities. These findings indicate that NSUN2 promotes gastric cancer progression by elevating m5C modification of ARMC9 mRNA, increasing its stability and enhancing its expression, therefore, NSUN2 and ARMC9 may serve as potential therapeutic targets for gastric cancer.

Background::Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo. This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. Methods::Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment.Results::Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t= 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001). Conclusions::Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca²⁺-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca²⁺ with an immune-regulating ability and CO₂ with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

To investigate the expression of miR-133a and miR-424 in the serum of patients with connective tissue disease(CTD)and interstitial lung disease(ILD)and their relationship with T lymphocyte subpopulations,total of 96 CTD-ILD patients treated in our hospital from December 2019 to December 2022 were selected as CTD-ILD group,while 96 CTD patients without ILD were as the control group.The real-time fluorescence quantitative PCR(qRT-PCR)method was applied to detect serum levels of miR-133a and miR-424;flow cytometry was applied to detect the levels of T lymphocyte subpopulations.Pearson method was applied to analyze the relationship of miR-133a and miR-424 with T lymphocyte subpopulations.Compared with the control group,the level of serum miR-133a in the CTD-ILD group was obviously reduced,while the expression level of miR-424 was obviously increased(P＜0.05).Under different degrees of pulmonary ventilation disorders,the expression level of miR-133a in the serum of mild,moderate,and severe patients decreased obviously,while the expression level of miR-424 increased obviously(P＜0.05).Under different grades of pulmonary diffusion dysfunction,the expression level of miR-133a in the serum of mild,moderate,and severe patients reduced obviously,while the expression level of miR-424 increased obviously(P＜0.05).Furthermore,the levels of CD4+and CD4+/CD8+in the CTD-ILD group were obviously increased,as compared to the control group,while the levels of CD8+and CD3+were obviously reduced(P＜0.05).In addition,miR-133a was negatively correlated with CD4+,and positively correlated with CD8+and CD3+;miR-424 was positively correlated with CD4+,and negatively correlated with CD8+and CD3+(P＜0.05).In conclusion,the expression level of miR-133a in serum of CTD-ILD patients is decreased,while the expression level of miR-424 is increased,and both of them are related to the T lymphocyte subpopulations.

Objective:To observe the effect of stellate ganglion block(SGB)on serum inflammatory factors and the expression of α7nAChR protein in rats with acute peritonitis,so as to further explore the mechanism of SGB on the inflammatory response of acute peritonitis in rats.Methods:40 SPF grade male rats were randomly divided into 4 groups:blank group(Control),acute peritonitis group(AP),acute peritonitis+stellate ganglion block group(AP+SGB),acute peritonitis+stellate ganglion block+α7nAChR inhibitor methyllycaconitine group(AP+SGB+MLA),with 10 rats in each group.Inject 2％acetic acid at a dose of 1 ml/100 g into the peritoneal cavity of rats to establish an acute peritonitis model in the AP group,AP+SGB group,and AP+SGB+MLA group.Blood samples were collected from the tail vein of the rats,and the concentrations of IL-18 and TNF-α in serum were detected by ELISA.Western Blot method was used to detect the level of α7nAChR protein in the peritoneal tissues,and RT-qPCR method was used to detect the expression of α7nAChR mRNA in the peritoneal tissues.Results:Compared with Control group,the levels of IL-18 and TNF-α were increased in the other three groups(P＜0.05).Compared with AP group,serum levels of IL-18 and TNF-α in AP+SGB group were decreased(P＜0.05).Compared with AP+SGB group,serum levels of IL-18 and TNF-α were increased in AP+SGB+MLA group(P＜0.05).The expression of α7nAChR mRNA protein were higher in the three groups than group Control,(P＜0.05).Compared with AP group,α7nAChR protein and α7nAChR mRNA expression levels were higher in AP+SGB group and AP+SGB+MLA group(P＜0.05).Compared with AP+SGB group,α7nAChR protein and α7nAChR mRNA expression levels in AP+SGB+MLA group were lower(P＜0.05).Conclusion:Stellate ganglion block treatment can reduce the production of inflammatory factors and inhibit the inflammatory response of acute peritonitis in rats,and its anti-inflammatory mechanism may be related to the cholinergic anti-inflammatory pathway(CAP)mediated by α7nAChR.