Objective: To investigate the objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease (DKD). Methods: A cross-sectional study enrolled 134 patients with DKD G3-5 stages who met the diagnostic criteria for damp-heat syndrome in DKD. The patients were treated at Dongzhimen Hospital, Beijing University of Chinese Medicine, from May 2023 to January 2024. The patients were divided into three groups: DKD G3, DKD G4, and DKD G5 stage, with 53, 33, and 48 patients in each group, respectively. Clinical general data (gender, age, and body mass index) and damp-heat syndrome scores were collected from the patients. The YZAI-02 traditional Chinese medicine (TCM) AI Tongue Image Acquisition Device was used to capture tongue images from these patients. The accompanying AI Open Platform for TCM Tongue Diagnosis of the device was used to analyze and extract tongue manifestation features, including objective data on tongue color, tongue quality, coating color, and coating texture. Clinical data and objective tongue manifestation characteristics were compared among patients with DKD G3-5 based on their DKD damp-heat syndrome status. Results: No statistically significant difference in gender or body mass index was observed among the three patient groups. The DKD G3 stage group had the highest age (P<0.05). The DKD G3 stage group had a lower score for symptoms of poor appetite and anorexia(P<0.05) than the DKD G5 group. No statistically significant difference was observed in damp-heat syndrome scores among the three groups. Compared with the DKD G5 stage group, the DKD G3 stage group showed a decreased proportion of pale color at the tip and edges of the tongue (P<0.05). The DKD G4 stage group exhibited an increased proportion of crimson at the root of the tongue, a decreased proportion of thick white tongue coating at the root, a decreased proportion of pale color at the tip and edges of the tongue, an increased hue value (indicating color tone) of the tongue color in the middle, an increased brightness value (indicating color lightness) of the tongue coating color in the middle, and an increased thickness of the tongue coating (P<0.05). No statistically significant difference was observed in other tongue color proportions, color chroma values, body characteristics, coating color proportions, coating color chroma values, and coating texture characteristics among the three groups. Conclusion Tongue features differ in different stages of DKD damp-heat syndrome in multiple dimensions, enabling the inference that during the DKD G5 stage, the degree of qi and blood deficiency in the kidneys, heart, lungs, liver, gallbladder, spleen, and stomach is prominent. Dampness is more likely to accumulate in the lower jiao, particularly in the kidneys, whereas heat evil in the spleen and stomach is the most severe. These insights provide novel ideas for the clinical treatment of DKD.

Objective: To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases. Methods: This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same. Results: ①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05). Conclusion Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.

Oral squamous cell carcinoma (OSCC), the most common type of head and neck malignancy, has a poor prognosis owing to its high invasiveness and high rate of cervical lymph node metastasis. The tumor microenvironment (TME) is a complex microenvironment that is essential for tumor cell survival. Tumor-associated immune cell (TAIC), the main stromal cell of TME, regulates the proliferation, invasion, epithelial-mesenchymal transformation (EMT), and anti-tumor immunity of OSCC. M2-tumor-associated macrophages (TAMs) promote the invasion and metastasis of OSCC through the macrophage migration inhibitory factor/NOD-like receptor family pyrin domain containing 3/interleukin (IL)-1β axis, while N2-tumor-associated neutrophils (TANs) regulate the proliferation and EMT of OSCC through the Janus kinase 2/signal transducer and activator of transcription 3 pathway. Meanwhile, myeloid-derived suppressor cells (MDSCs) accelerate the progression of OSCC by secreting IL-6, IL-10, and transforming growth factor (TGF)-β; T cells promote inflammation by secreting IL-17 and inhibit inflammation-mediated tumor immune response by secreting IL-10 and TGF-β; and natural killer (NK) cells recognize and attack OSCC cells to inhibit OSCC progression. TAIC interaction network also regulates OSCC progression. M2-TAMs regulate the invasion and metastasis of OSCC by promoting T cell apoptosis through the secretion of IL-10 and programmed death-ligand (PD-L) -1, while N2-TANs inhibit T cell proliferation and cytotoxicity by secreting LOX-1 and arginase-1. MDSCs inhibit the proliferation and anti-tumor effects of CD8+ T cells through the inactivation of programmed cell death (PD)-1/PD-L1 signaling. Additionally, MDSCs inhibit the proliferation of T cells by decreasing the expression of the CD3-zeta chain and interferon-γ (IFN-γ). Moreover, tumor-infiltrating lymphocytes and NK cells were found to be positively correlated in OSCC progression. Therefore, target regulation, related signaling pathways, and the interaction network of TAIC may serve as promising therapeutic targets in the immunotherapy of OSCC. In this review, we summarize the recent research on the effects of TAIC and their interaction network in the TME in the progression of OSCC and explore its application in the early diagnosis and treatment of OSCC

OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis （UC） mice based on adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS Male BALB/c mice were randomly divided into control group， model group， inhibitor group （AMPK inhibitor Compound C 20 mg/kg）， paeoniflorin low-， medium- and high-dose groups （paeoniflorin 12.5， 25， 50 mg/kg）， high- dose of paeoniflorin+inhibitor group （paeoniflorin 50 mg/kg+Compound C 20 mg/kg）， with 8 mice in each group. Except for the control group， mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently， mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally， once a day， for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration， colon length， malondialdehyde （MDA） content， and activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in colon tissues were measured； histopathological morphology of colon tissues， tight junctions between intestinal epithelial cells， and histopathological scoring were all observed and evaluated； the mRNA expressions of AMPK and Nrf2， as well as the protein expressions of heme oxygenase-1（HO-1）， occludin and claudin-1， were all determined in colon tissue. RESULTS Compared with model group， paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue， as well as improved tight junction damage between intestinal epithelial cells. Additionally， significant increases or upregulations were observed in body weight， colon length， activities of SOD and GSH-Px， phosphorylation level of AMPK， and protein expression of Nrf2， HO-1， occludin， claudin-1， and mRNA expressions of AMPK and Nrf2； concurrently， MDA content and histopathological scores were significantly reduced （P＜ 0.05 or P＜0.01）. In contrast， the inhibitor group showed comparable （P＞0.05） or worse （P＜0.05 or P＜0.01） indicators compared to the model group. Conversely， the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin （P＜0.01）. CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice， improve tight junctions between epithelial cells， upregulate the expression of related proteins， and promote the expression and secretion of antioxidant-promoting molecules， thereby ameliorating UC； its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.

OBJECTIVE To evaluate the cost-effectiveness of toripalimab combined with paclitaxel （albumin binding type） in the treatment of metastatic or recurrent triple-negative breast cancer （TNBC）. METHODS Based on the data of TORCHLIGHT clinical trial， a three-state partitioned survival model including progression-free survival， disease progression， and death was established. The simulation cycle was 21 days， the study duration was 10 years， and the discount rate was 5%. Using quality- adjusted life year （QALY） and cost as output indicators， a cost-effectiveness analysis method was adopted to calculate the incremental cost-effectiveness ratio （ICER） of toripalimab combined with paclitaxel （albumin binding type） versus placebo combined with paclitaxel （albumin binding type）. Using three times the per capita gross domestic product （GDP） of China in 2023 as the willingness-to-pay（WTP） threshold（268 074 yuan/QALY）， the cost-effectiveness of the above two regimens was evaluated， and the sensitivity analysis was conducted. RESULTS ICER of toripalimab combined with paclitaxel （albumin binding type） versus placebo combined with paclitaxel （albumin binding type） in the treatment of Chinese metastatic or recurrent TNBC patients was 176 347.17 yuan/QALY， which was lower than the WTP threshold set in this study， demonstrating the cost-effectiveness of this regimen. The results of the single-factor sensitivity analysis showed that the parameters such as the cost of toripalimab， discount rate， and utility value of the progression-free survival state had a great impact on the ICER. The results of the probabilistic sensitivity analysis indicated that the results of the basic analysis were robust. CONCLUSIONS When three times the per capita GDP of China in 2023 is used as the WTP threshold， compared with the regimen of placebo combined with paclitaxel （albumin binding type）， toripalimab combined with paclitaxel （albumin binding type） is cost-effective in the treatment of metastatic or recurrent TNBC.

ObjectiveTo investigate the mechanism by which Mingshi prescription regulates the retinal melanopsin-dopamine （Opn4-DA） axis in myopic mice to inhibit endoplasmic reticulum （ER） stress in the retina and sclera， thereby delaying axial elongation associated with myopia. MethodsSixty 4-week-old male SPF-grade C57BL/6J mice were randomly divided into a normal group， a form-deprived myopia group （FDM group）， an intrinsically photosensitive retinal ganglion cells ablation group （ipRGCs group）， a Mingshi Prescription group （MSF group， 5.2 g·kg^-1）， and an ipRGCs + MSF group （5.2 g·kg^-1）. Except for the normal group， all other groups underwent FDM modeling. Additionally， the ipRGCs and ipRGCs + MSF groups received retinal ipRGC ablation. Three weeks after modeling， the MSF and ipRGCs + MSF groups were administered Mingshi prescription via continuous gavage for six weeks. After refraction and axial length were measured in all mice， eyeballs were collected along with retinal and scleral tissues. Pathological and morphological changes in the retina， choroid， and sclera were observed using periodic acid-Schiff （PAS） staining. Western blot was employed to detect the relative protein expression levels of dopamine D1 receptor （DRD1）， C/EBP homologous protein （CHOP）， and glucose-regulated protein 78 （GRP78） in the retina， and CHOP and GRP78 in the sclera. Real-time PCR was used to detect the relative mRNA expression of Opn4， CHOP， and GRP78 in the retina， and CHOP and GRP78 in the sclera. Immunofluorescence staining （IF） was performed to detect the expression of Opn4 and DRD1 in retinal tissues. ResultsCompared with the normal group， the FDM group showed a significant myopic shift in refraction （P<0.05） and a significant increase in axial length （P<0.05）. The retinal layers were thinner， the number of ganglion cells was reduced， and collagen fibers in the sclera were loosely arranged with evident gaps. Opn4 and DRD1 protein and mRNA expression in the retina were significantly decreased （P<0.05）， while CHOP and GRP78 protein and mRNA expression in both retinal and scleral tissues were significantly increased （P<0.05）. Compared with the FDM group， the ipRGCs group exhibited further increases in myopic refraction and axial length （P<0.05）， more pronounced thinning and looseness in the retinal， choroidal， and scleral layers， lower expression of Opn4 and DRD1 protein and mRNA in the retina （P<0.05）， and higher expression of CHOP and GRP78 protein and mRNA in the retina and sclera （P<0.05）. Compared with the FDM group， the MSF group showed significantly reduced refractive error and axial length （P<0.05）， with improved cellular number， arrangement， and thickness in ocular tissues， increased Opn4 and DRD1 protein and mRNA expression in the retina （P<0.05）， and reduced CHOP and GRP78 protein and mRNA expression in both retina and sclera （P<0.05）. Similarly， the ipRGCs + MSF group showed significant improvements in terms of the above items compared with the ipRGCs group （P<0.05）. ConclusionMingshi Prescription delays myopic axial elongation and refractive progression by regulating the Opn4-DA axis in the retina of myopic mice， thereby inhibiting ER stress in the retina and sclera. This intervention promotes Qi and blood nourishment of the eyes， softens the fascia， and restores ocular rhythm.

Thyroid cancer is caused by multiple factors, including genetics, environment, metabolism, and the immune microenvironment, among which ionizing radiation exposure is an important risk factor for thyroid cancer. As one of the most sensitive target organs of ionizing radiation, the thyroid gland may have different risks of thyroid cancer caused by different types of ionizing radiation exposures, such as medical exposure, occupational exposure, and emergency exposure. The sensitivity of children and adolescents are higher than that of adults. The dose-response relationship still needs to be further explored. The molecular mechanism between ionizing radiation and the increased risk of thyroid cancer is complex, which may involve DNA damage and repair abnormalities, gene mutations, non-coding RNA regulation, DNA methylation, cell cycle regulation imbalance, and immune microenvironment changes. This article reviews the risk and molecular mechanisms associated with different types of ionizing radiation exposure in thyroid cancer, based on literature retrieved from CNKI and PubMed databases. It aims to provide a theoretical basis for the early monitoring, prevention, and intervention of thyroid cancer related to ionizing radiation exposure.

Objective To observe the changes to,and possible mechanism of,intestinal permeability in pigs without direct injury after an abdominal-and intestinal-penetrating injury from firearms in cold environment at high altitudes.Methods Fifty-five experimental pigs were divided into two groups:high-altitude cold group(HC)and low-altitude normal temperature group(LN).According to the observation time,each group was divided into five experimental subgroups:0h,2h,4 h,8h,and 24 h.There were six pigs in each HC subgroup and five pigs in each LN subgroup.After euthanasia,intestinal tissues were taken,and the levels of the inflammatory factors TNF-α,and IL-6 in intestinal homogenate and the concentrations of intestinal permeability-related proteins DAO and D-lactate acid in blood were detected by ELISA method.The intestinal tissues of experimental pigs were taken at 0 h and 8 h for LN and 8 h for HC,and intestinal pathological changes were observed and scored after HE staining.The concentrations of Occludin,ZO-1,Claudin-3,TLR4,NF-κB,and MLCK(proteins related to intestinal permeability)were detected by Western blot to explore the effect of a cold environment at high altitude on secondary intestinal permeability changes after injury and the possible mechanisms.Results Both the HC group and LN group experienced typical abdominal intestinal penetrating injuries,and there were no significant differences in their abdominal infection scores or intestinal adhesion(P＞0.05).The levels of DAO and D-LA in the serum of experimental pigs in the HC and LN groups gradually increased over time.The levels of DAO and D-LA in the HC group were significantly higher than those in the LN group at all time points(P＜0.01 or P＜0.001).The fastest increase in DAO and D-LA in the HC group was 4 h to 8 h,while in the LN group,it was 8 h to 24 h.The pathological score of intestinal tissue in the HC group was significantly higher than that in the LN group of experimental pigs(P＜0.01).The inflammatory factors TNF-α and IL-6 both increased over time in the intestinal tissue of LN and HC groups.The most significant time point for a increase of inflammatory factors in the HC group was 4 h to 8 h,while in the LN group,it was 8 h to 24 h.The intestinal tissue IL-6 and TNF-α levels of experimental pigs in the HC group were higher than those in the LN group the entire time(P＜0.05,P＜0.01,or P＜0.001).The levels of occludin and ZO-1 in the HC group at 8 h decreased significantly compared to those of the LN group at the 8 h time point(P＜0.05),while claudin-3 showed a significant decrease in LN(P＜0.001).In the HC group,TLR4,NF-κB,and MLCK were both higher than those in the LN group at 8 h,and the difference was statistically significant(P＜0.05).Conclusions A high-altitude cold environment can lead to a secondary increase in intestinal permeability after abdominal-penetrating firearm injury,and its mechanism may be related to the TLR4/NF-κB/MLCK pathway.

Objective To explore the application effect of advanced lung rehabilitation programs in patients un-dergoing high flow nasal cannula oxygen therapy(HFNC).Methods Convenience sampling method was used to se-lect 40 HFNC patients admitted to the respiratory department,ICU,coronary heart disease monitoring unit,and other departments of a tertiary A comprehensive hospital in Tianjin from January to June 2023 as the experimental group,and 40 HFNC patients admitted from June to December 2022 as the control group.Both groups of patients received HFNC treatment during hospitalization and continued at home,while the experimental group adopts the information-motivation-behavioral skills(IMB)model as the theoretical basis,implements advanced pulmonary rehabili-tation during the stable condition period,discharge preparation period,and home rehabilitation period,and imple-ments compliance management of home pulmonary rehabilitation through cloud follow-up,and the control group re-ceived routine lung rehabilitation and home follow-up.The degree of respiratory distress,6-minute walking distance,exercise self-efficacy,quality of life were compared between the 2 groups before intervention,2 months and 6 months after intervention,and compliance with home pulmonary rehabilitation was compared between the 2 groups 6 months after intervention.Results The repeated measures analysis of variance showed that there was an interaction effect between time and the 2 groups in terms of difficulty in breathing,6-minute walking distance,exercise self-ef-ficacy,and quality of life(P＜0.05).Simple effect analysis showed that after 2 and 6 months of intervention,the ex-perimental group performed better than the control group in the respiratory distress,6-minute walking distance,exer-cise self-efficacy,and quality of life(P＜0.05).Within 6 months of intervention,the compliance of home pulmonary rehabilitation in the experimental group was better than that in the control group,and the difference was statistically significant(P＜0.05).Conclusion The application of advanced pulmonary rehabilitation programme based on IMB can improve respiratory symptoms and improve exercise self-efficacy and adherence to pulmonary rehabilitation,en-hance activity endurance and improve quality of life.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.