OBJECTIVE To provide references for the accurate identification and management of immune-related cutaneous adverse events （irCAEs） caused by durvalumab， and ensuring safe clinical drug use. METHODS Clinical pharmacists participated in the diagnosis and treatment process of a patient with gallbladder cancer who developed irCAEs caused by durvalumab. The clinical pharmacists systematically reviewed the patient’s past medical history and medication history， and assisted physicians in assessing the association between adverse drug reactions and administered drugs. Meanwhile， the clinical pharmacists conducted a graded assessment of the adverse reaction， proposed recommendations such as discontinuing durvalumab and adjusting the administration regimen of glucocorticoids， assisted physicians in restarting immunotherapy， and carried out medication education and other pharmaceutical care. RESULTS The occurrence of irCAEs in this patient was “highly likely” related to durvalumab and was classified as severe. The physicians adopted the clinical pharmacist’s opinion， and after symptomatic treatment， the patient’s skin symptoms improved， and discharged with medication. After the completion of glucocorticoid therapy for the patient， the physician restarted immunotherapy with tislelizumab， and no related adverse reactions occurred again in the patient. CONCLUSIONS Durvalumab can cause irCAEs such as severe skin maculopapular rash. In clinical practice， it is crucial to promptly identify and discontinue suspicious drugs， immediately implement effective symptomatic treatment measures， and actively resume immunotherapy to ensure the continuity and safety of the patient’s treatment.

Narrow leaf 1 (NAL1) plays an important role in plant branching, while little is known about the roles of this gene in petunias. In this study, PhNAL1b was cloned from Petunia×hybrida cv. Mitchell Diploid, with a total length of 1 767 bp, encoding a protein composed of 588 amino acid residues and containing the peptidase S64 domain. The PhNAL1b promoter region contained several elements involved in the responses to auxin, jasmonic acid, abscisic acid, and light. The expression analysis showed that PhNAL1b had the highest expression level in roots and the lowest expression level in flowers, and its transcription could be inhibited by decapitation and cytokinin. The subcellular localization analysis showed that PhNAL1b was located in the nucleus and was a nuclear protein. Virus-induced gene silencing was employed to downregulate the expression of PhNAL1b, which resulted in significant increases in branch number and plant height. The results indicated that PhNAL1b played an important role in regulating the branching of petunias. This study lays a foundation for revealing the mechanism of NAL1 in regulating branch development and provides genetic resources for plant architecture improvement.
Petunia/growth & development* ; Plant Proteins/metabolism* ; Diploidy ; Gene Expression Regulation, Plant ; Cloning, Molecular ; Promoter Regions, Genetic

Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.

Objective : To investigate the role of AdipoRon, an adiponectin receptor agonist, in treatment of carbon tetrachloride(CCl4) induced liver fibrosis mice model and the mechanisms. Methods : Forty mice were randomly divided into control group, model group, L-AdipoRon group and H-AdipoRon group, with 10 mice in each group. Hepatic fibrosis was induced by intraperitoneal injection of CCl4solution. The mice in L-and H-AdipoRon groups were given 100 mg/kg and 200 mg/kg AdipoRon by gavage, respectively. The activities of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were detected by biochemical method. Liver histopathological changes and fibrosis were detected by HE staining, Masson staining and Sirius scarlet stain. The protein expression levels of Collagen I, α-smooth muscle actin(α-SMA), matrix metalloproteinase 1(MMP-1) and matrix metalloproteinase inhibitor 1(TIMP-1) in mice liver were detected by Western blot. Lipid deposition in liver were detected by oil red O staining. The percentage(%) of CD68+ iNOS+ positive M1-type macrophages in the liver were detected by immunofluorescence. The expression levels of fatty acid synthetase(Fasn), stearoyl-CoA desaturase 1(Scd1), fatty acid transporter(Cd36), peroxissome proliferator activated receptor-α(Pparα) and carnitine palmitoyl transferase 1α(Cpt1α) in mice liver tissues, as well as M1 macrophage-related genes interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) and M2 macrophage-related genes arginase 1(Arg1), Chil3 chitinase-like 3(Ym-1) were detected by RT-qPCR assay. Results : Compared with model group, in low-dose AdipoRon group and high-dose AdipoRon group, serum ALT and AST activities significantly decreased(P<0.05); liver tissues structure were damaged, liver cells degeneration and inflammatory cells infiltration were improved; collagen fiber deposition was also significantly reduced; the relative expression levels of Collagen I, α-SMA and TIMP-1 proteins were significantly down-regulated(P<0.05), while the relative expression levels of MMP-1 protein were significantly up-regulated(P<0.05); the lipid droplets deposition in livers were significantly reduced. The relative Fasn, Scd1 and Cd36 mRNA expression levels in liver tissues were significantly down-regulated(P<0.05), and the relative Pparα and Cpt1α mRNA expression levels were significantly up-regulated(P<0.05); the percentage(%) of CD68+ iNOS+ positive M1-type macrophages significantly decreased(P<0.05); the relative IL-6 and TNF-α mRNA expression levels significantly decreased(P<0.05), the relative Arg1 and Ym-1 mRNA expression levels were significantly up-regulated(P<0.05). In addition, the improvement effects of high-dose AdipoRon group were better than those of low-dose AdipoRon group(P<0.05). Conclusion AdipoRon can improve the disorder of lipid metabolisms, inhibit the M1 type macrophages polarization, and improve the liver fibrosis in CCl4-induced liver fibrosis mice model.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

Objective"Red butterfly sore","yin-yang toxin"and"Bi disease"are different Chinese medicine diagnoses of systemic lupus erythematosus(SLE).It is not clear whether there are biological differences between these three types of Chinese medicine diagnoses.The aim of this study was to compare the different TCM diagnoses of SLE patients from the perspective of lymphocyte subsets and cytokines.Methods Patients diagnosed with SLE in our hospital from June 1,2021 to December 1,2023 were retrospectively collected,and the differences of T cell subsets,NK cells,B lymphocytes and Th1,Th2 and Th17 cytokines among different groups were compared by one-way ANOVA or nonparametric test.As well as differences in laboratory test indicators such as erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),immunoglobulin,and complement,receiver operating characteristic curve(ROC curve)was used to analyze the value of these indexes in the differential diagnosis of different types of SLE.Results From June 1,2021 to December 1,2023,291 patients diagnosed with SLE in our hospital for the first time were collected,and 104 cases meeting the exclusion criteria of this study were included,including 31 cases of red butterfly sores,30 cases of yin-yang toxin and 43 cases of BI disease.The absolute number and percentage of CD8+T cells,interleukin-10(IL-10)content and tumor necrosis factor α(TNF-α)content were different among the three groups of SLE patients diagnosed by different Chinese medicine,and the absolute number of CD8+T cells in the red butterfly sore group was significantly higher than that in the yin-yang toxicities group(P=0.039)and the disease group(P=0.008).CD8+T cell percentage in red butterfly sore group was significantly higher than that in yin-yang toxin group(P=0.014)and disease group(P=0.004),IL-10 and TNF-α levels in red butterfly sore group were significantly lower than those in disease group(P=0.015,P=0.036),and ROC curve analysis showed that,the absolute number and percentage of CD8+T cells can effectively distinguish red butterfly sores from yin-yang toxins(AUC=0.65,AUC=0.61,P<0.05),and the absolute number and percentage of CD8+T cells,IL-10 and TNF-α can effectively distinguish red butterfly sores from diseases(AUC=0.68,AUC=0.66,P<0.01,AUC=0.67,AUC=0.64,P<0.05).Conclusion Immune lymphocyte subtypes,cytokines,especially the absolute number and percentage of CD8+T cells,IL-10 and TNF-α may play an important role in the identification of different TCM diagnosis of SLE.

Objective To investigate the effect of atractylenolide Ⅱ regulated Yes associated protein(YAP)signaling pathway on joint function and splenic regulatory T cells(Treg)/helper T cell 17(Th17)expression in rheumatoid arthritis(RA)model rats.Methods The RA rat model was constructed,and SD rats were separated into a control group,a model group,a low-dose atractylenolide Ⅱ group(10 mg/kg/d),a high-dose atractylenolide Ⅱ group(50 mg/kg/d),and a high-dose atractylenolideⅡ+YAP activator(PY60)group.On the 1st,7th and 14th day of the dosing period,rats were weighed and the joint swelling rate was evaluated,the arthritis index was scored after administration;HE staining was applied to observe pathological changes;flow cytometry was applied to detect the proportions of Treg and Th17 cells in splenic tissue;Western blot(WB)was applied to detect the expression levels of phosphorylation(p)in metatarsal tissue-mammalian STE20-like protein kinase 1(p-MST1),MST1,phospho-large tumor suppressor gene 1(p-LATS1),LATS1,phospho-Yes associated protein(p-YAP)and YAP proteins.Results Compared with the control group,rats in the model group suffered from damage to the metatarsal cartilage tissue,resulting in weight loss and increased joint swelling rate during the administration period,during the administration period,the body weight was lower and the joint swelling rate was higher,the arthritis index score,Mankin score,proportion of spleen Th17 cells,and the expression level of metatarsal p-YAP/YAP protein were higher,the proportion of Treg cells and the expression levels of p-MST1/MST1 and p-LATS1/LATS1 proteins were lower,and the differences were statistically significant(t=4.953～38.268,all P<0.05).Compared with the model group,the cartilage tissue damage in the low and high dose atractylenolide Ⅱ groups was reduced,during the administration period,the body weight was higher and the joint swelling rate was lower,the arthritis index score,Mankin score,proportion of spleen Th17 cells,and the expression level of metatarsal p-YAP/YAP protein were lower,the proportion of Treg cells and the expression levels of p-MST1/MST1 and p-LATS1/LATS1 proteins were higher,the differences were statistically significant(tlow dose=4.050～17.013,thigh dose=6.379～32.174,all P<0.05).Compared to the high-dose atractylenolide Ⅱ group,the damage to the cartilage tissue of the metatarsal bone in the high-dose atractylenolideⅡ+PY60 group was worsened,during the administration period,the body weight was lower and the joint swelling rate was higher,the arthritis index score,Mankin score,proportion of spleen Th17 cells,and the expression level of metatarsal p-YAP/YAP protein were higher,the proportion of Treg cells and the expression levels of p-MST1/MST1 and p-LATS1/LATS1 proteins were lower,and the differences were statistically significant(t=5.084～27.703,all P<0.05).Conclusion Atractylenolide Ⅱ inhibits the activation of YAP signaling pathway,regulates splenic Treg/Th17 cell balance and ameliorates disease progression in RA rats.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

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.