ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss （RPL） by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus （Shoutai Wan， Juyuan Jian）-of traditional Chinese medicine （TCM） at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c （blank group） and DBA/2 （modeling group） mice separately. Pregnant mice in the modeling group were randomly grouped as follows： high/low-dose Shoutai Wan， high/low-dose Juyuan Jian， model （RPL）， and positive control （dydrogesterone）， with 10 mice in each group. Starting from the day after the detection of the vaginal plug， mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention， the following indicators were measured. ① Macroscopic evaluation： general conditions， uterine wet weight， embryo loss rate， four coagulation parameters ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， fibrinogen （FIB）， and thrombin time （TT）］， and peripheral blood estradiol （E₂） and progesterone （Pg） levels. The decidua with embryos was stained with hematoxylin-eosin （HE） and evaluated by transmission electron microscopy （TEM）. The expression of B-cell lymphoma-2 （Bcl-2）， vascular endothelial growth factor （VEGF）， angiotensin Ⅱ （AngⅡ）， matrix metalloproteinase-2 （MMP-2）， interleukin-6 （IL-6）， leukemia inhibitory factor （LIF）， CXC chemokine ligand 12 （CXCL12）， and microtubule-associated protein 1 light chain 3 homolog （LC3）Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level： The decidua with embryos from the blank， model， high-dose Shoutai Wan， and high-dose Juyuan Jian groups （6 mice per group， with 3 single-cell samples per group， totaling 24 mice） were analyzed by the BD Rhapsody™ platform， and the whole-cell atlas was drawn by uniform manifold approximation and projection （UMAP） dimensionality reduction clustering combined with the single-cell mouse cell atlas （scMCA）. The differentially expressed genes （DEGs） and cell interaction networks were analyzed via Gene Ontology （GO）， Kyoto Encyclopedia of Genes and Genomes （KEGG）， and CellChat， and the protein-protein interaction （PPI） map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells （natural killer cells， NK cells） from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group， the RPL group showed an increase in the embryo loss rate （P<0.01）， down-regulated expression of Bcl-2， LIF， MMP-2， and Vegf in the decidua with embryos （P<0.05）， up-regulated protein levels of CXCL-12， AngⅡ， and IL-6 （P<0.05）， blocked angiogenesis， apoptosis-inflammation imbalance， and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance， and Shoutai pill showed superior performance in restoring the E₂ level to the Pg level （P<0.05）. ② Single-cell transcriptome analysis indicated that compared with the blank group， the RPL group showed differences in multiple key cell populations such as decidual cells， trophoblast cells， endothelial cells， erythroblasts， NK cells， and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group， high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer （upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes） and macrophages （upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes） through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins， cell adhesion， and programmed cell death， thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells （up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes） and macrophages （up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes）， which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D， CDH5， GDF， and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 （STAT3） and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis （TWEAK） signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7， a decreased proportion of reparative dNK4， and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1， thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method （Shoutai Wan） has an advantage in regulating the phenotypes of unfolded protein， cell adhesion， and programmed cell death， and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method （Juyuan Jian） has an advantage in regulating epithelial-mesenchymal transition （EMT）， angiogenesis， and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

Objective To explore the effect of diet therapy on alcohol-induced chronic liver injury in rats and its relationship with TLR4 pathway.Methods According to Pueraria:Poria:Amomum villosum:Pericarpium Citri Reticulatae:Codonopsis:Zingiberis Rhizoma=15∶15∶10∶10∶10∶6,the water extract of the therapeutic prescription was prepared.A total of 78 female SD rats were randomly divided into 6 groups:normal group(n=12),model group(n=18),Hugan tablet group(0.35 g·kg-1,n=12),low-,medium-and high-dose Shiliaofang groups(2,6,18 g·kg-1,n=12).Except for the normal group,the rats in each group were induced alcoholic liver disease(ALD)by gradient alcohol gavage.After 10 weeks of intervention,the changes of body weight and water intake of rats were observed.The whole blood routine,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC)and liver malondialdehyde(MDA)were measured.The levels of serum alcohol dehydrogenase(ADH),aldehyde dehydrogenase(ALDH),lipopolysaccharide(LPS),D-lactic acid(D-LA),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay.HE staining was used to observe the pathological changes of liver and ileum.Oil red staining was used to observe liver fat deposition.Immunohistochemistry was used to detect the expression of ileal tight junction component occludin.Western blot was used to detect the expression of TLR4,MyD88 and NF-κB p65 protein in liver.Results Compared with the model group,the levels of WBC,LYC,TC,ALT,AST,LPS,D-LA,TNF-α and IL-6 in each diet group decreased,IL-10 increased,liver inflammatory cell infiltration and red lipid droplets decreased,intestinal villi were intact and densely arranged,the expression of occludin protein in ileum increased,and the expression of TLR4,MyD88 and NF-κB p65 protein in liver decreased.Conclusion The self-made dietotherapy prescription has a significant protective effect on chronic liver injury induced by alcohol in rats,which may be related to its down-regulation of TLR4-MyD88-NF-κB p65 protein expression and up-regulation of ileal occludin protein expression,improvement of intestinal mucosal barrier function,reduction of endotoxin entry into the liver,activation of TLR4/MyD88/NF-κB pathway,thereby reducing the second hit to the liver.This diet can be developed as a potential anti-alcoholic liver injury drug.

Objective To investigate the effects of three types of twin-block(TB)appliances on the stress and displacement of anterior teeth,periodontal ligaments,and alveolar bone.Methods A three-dimensional(3D)finite element model was constructed,including maxillofacial bones,articular discs,teeth,and periodontal ligaments.Three types of twin-block appliances were designed:classic twin-block(classic-TB),twin-block with acrylic capping(capping-TB),and clear twin-block aligner(CTBA).All appliances had an inclination angle of 70°,and a masticatory force of 200 N was applied to their inclined planes.The finite element method was used to analyze the stress distribution and displacement differences of anterior teeth.Results All three types of TB appliances induced lingual tilting of maxillary anterior teeth and labial tilting of mandibular anterior teeth.The CTBA group showed the greatest lingual displacement and stress of maxillary anterior teeth,with a maximum stress of 30.6 MPa,while the mandibular anterior teeth in this group exhibited the smallest labial displacement(approximately 0.02 mm)and stress.Additionally,the CTBA group had the lowest compressive stress in mandibular anterior teeth,periodontal ligaments,and alveolar bone,whereas the classic-TB group had the highest.Conclusions In the treatment of Angle Class Ⅱ malocclusion,classic-TB(with or without acrylic capping)causes labial inclination of mandibular anterior teeth.Compared with classic-TB,CTBA effectively reduces the compressive stress and displacement of mandibular anterior teeth,potentially minimizing adverse periodontal risks.However,attention should be paid to the lingual displacement of maxillary anterior teeth.

Objective To observe the value of intravoxel incoherent motion(IVIM)histogram parameters for predicting perineural invasion(PNI)of rectal cancer.Methods Fifty-five patients with rectal cancer were retrospectively enrolled and divided into positive group(n=23)and negative group(n=32)according to PNI or not.Histogram parameters of apparent diffusion coefficient(ADC),perfusion fraction(f),true diffusion coefficient(D)and pseudo diffusion coefficient(D*)were obtained based on MR IVIM images,including the mean,skewness,kurtosis,entropy,as well as the 25th,50th and 75th percentiles(25th,50th,75th).The above IVIM histogram parameters were compared between groups,and those with significant difference were included in binary stepwise logistic regression analysis to screen independent factors for predicting PNI status of rectal cancer.Then a combined parameter model was established.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of IVIM histogram parameters and combined parameter model for predicting PNI of rectal cancer.Results ADCmean,ADC25th,ADC50th,ADC75th,fmean,f25th,f50th,f75th and Dentropy in positive group were all lower than those in negative group(all P＜0.05).AUC of the above parameters for predicting PNI of rectal cancer was 0.693,0.665,0.701,0.675,0.831,0.847,0.835,0.722 and 0.785,respectively.The sensitivity,specificity and AUC of combined parameter model based on f25th and Dentropy for predicting PNI of rectal cancer was 95.65％,65.63％and 0.897,respectively.Conclusion IVIM histogram parameters could be used to predict PNI of rectal cancer effectively.

Objective:To investigate the effects of short-peptide-based enteral nutrition on nutritional status, immune function, and chemotherapy-related adverse reactions in children with acute lymphoblastic leukemia (ALL).Methods:A total of 106 children with ALL receiving chemotherapy at the Affiliated Hospital of Jining Medical University between January 2021 and April 2022 were enrolled. According to the principle of between-group baseline data matching, the patients were divided into observation group and control group by random number table method, with 53 cases in each group. All patients received chemotherapy according to the CCCG-ALL-2020 protocol established by the Multi-center Cooperative Group of the Chinese Society of Pediatric Oncology (2020). The control group received a regular diet, while the observation group received a regular diet supplemented with short-peptide-based enteral nutrition. The incidence rates of malnutrition, hypoproteinemia, hypoalbuminemia, abnormal immunoglobulin levels (IgG, IgM, IgA), and adverse reactions (liver injury, infection) were compared between both groups before chemotherapy and at the end of each of the following seven chemotherapy phases: Induction remission therapy (PVDL), Induction remission therapy (CAT), Early intensification therapy (CAT+), Consolidation therapy (HDMTX), Interim maintenance therapy, Reinduction therapy, and prior to the end of Maintenance therapy. Normally or approximately normally distributed measurement data were expressed as xˉ± s and compared by independent samples t-test. Counting data were expressed as n (%) and compared by χ2 test. Results:During the CAT phase, the incidence of malnutrition was significantly lower in the observation group than in the control group [20.8% (11/53) vs. 39.6% (21/53), χ2=4.48, P=0.034]. The incidence of hypoproteinemia was significantly lower in the observation group during HDMTX, Reinduction, Interim maintenance, and prior to the end of Maintenance therapy [47.2% (25/53) vs. 69.8% (37/53), χ2=5.60, P=0.018; 45.3% (24/53) vs. 67.9% (36/53), χ2=5.53, P=0.019; 41.5% (24/53) vs. 64.2% (34/53), χ2=5.45, P=0.020; 28.3% (15/53) vs. 54.7% (29/53), χ2=7.62, P=0.006, respectively]. The incidence of hypoalbuminemia was significantly lower in the observation group during CAT+, HDMTX, Reinduction, Interim maintenance, and prior to the end of Maintenance therapy [5.7% (3/53) vs. 22.6% (12/53), χ2=6.29, P=0.012; 9.4% (5/53) vs. 26.4% (14/53), χ2=5.19, P=0.023; 9.4% (5/53) vs. 28.3% (15/53), χ2=6.16, P=0.013; 7.6% (4/53) vs. 24.5% (13/53), χ2=5.68, P=0.017; 3.8% (2/53) vs. 18.9% (10/53), χ2=6.01, P=0.014, respectively]. For IgG, incidence was significantly lower in the observation group during Interim maintenance, Reinduction, and prior to the end of Maintenance therapy [7.6% (4/53) vs. 22.6% (12/53), χ2=4.71, P=0.030; 20.8% (11/53) vs. 39.6% (21/53), χ2=4.48, P=0.034; 11.3% (6/53) vs. 26.4% (14/53), χ2=3.94, P=0.047, respectively]. For IgM, incidence was significantly lower in the observation group during the CAT and CAT+ phases [45.3% (24/53) vs. 66.0% (35/53), χ2=4.63, P=0.032; 58.5% (31/53) vs. 77.4% (41/53), χ2=4.33, P=0.037, respectively]. For IgA, incidence was significantly lower in the observation group during Reinduction therapy and Interim maintenance [22.6% (12/53) vs. 45.3% (24/53), χ2=6.06, P=0.014; 9.4% (5/53) vs. 24.5% (13/53), χ2=4.28, P=0.038, respectively]. For liver injury, incidence was significantly lower in the observation group during the CAT, CAT+, and prior to the end of Maintenance phases [22.6% (12/53) vs. 43.4% (23/53), χ2=5.16, P=0.023; 26.4% (14/53) vs. 50.9% (27/53), χ2=6.72, P=0.010, 11.3% (6/53) vs. 26.4%(14/53), χ2=3.94、 P=0.047,respectively]. For infection, incidence was significantly lower in the observation group during the CAT+ and HDMTX phases [35.9% (19/53) vs. 56.6% (30/53), χ2=4.59, P=0.032; 24.5% (13/53) vs. 43.4% (23/53), χ2=4.21, P=0.040, respectively]. Conclusions:Short-peptide-based enteral nutrition demonstrates significant advantages in the treatment of pediatric ALL. It provides substantial support for patient treatment and recovery by improving nutritional status, modulating immune function, and reducing chemotherapy-related adverse reactions.

A 20-year-old male patient with T-lymphoblastic lymphoma/leukemia received 9/10 human leukocyte antigen-compatible unrelated peripheral blood stem cell transplantation. He was transplanted with 5.91×10 8 mononuclear cells/kg and 2.88×10 6 CD34 + cells/kg, and neutrophil engraftment was obtained at +11 days and platelet engraftment at +9 days. After transplantation, he presented with repeatedly increased serum creatinine levels, BK virus (BKV) -associated hemorrhagic cystitis, and BKV viremia. BK virus nephropathy was diagnosed based on renal biopsy and metagenomic next-generation sequencing. After adjusting the immunosuppressant, intravenous immunoglobulin, and donor lymphocyte infusion treatment, the patient’s renal function deteriorated progressively, and he eventually died of multiple organ failure at +289 days.

Objective To delineate the current research landscape,emerging hotspots,and frontiers re-garding the relationship between the oral microbiome and digestive system diseases.Methods We retrieved publications from the Web of Science Core Collection database using topic-specific queries on"oral microbi-ome"and"digestive diseases."Bibliometric analysis was performed using VOSviewer,CiteSpace,and the"bibliometrix"package in R for data mining and visualization.Results A total of 1228 eligible articles were included.Analysis revealed that research on the correlation between oral microbiota and digestive system diseases will remain a global hotspot.Academic institutions dominated the publications,with centralized institutional distribution and team-based collaboration,though overall collaboration networks remained fragmented.Geo-graphically,the United States emerged as the leading contributor,followed by China and the United Kingdom.While China-U.S.collaborations were prominent,China's engagement with other regions remained limited.Current research hotspots focus on the interplay between oral microbiota and gut microbiota,inflam-matory bowel disease(IBD),and digestive system tumors.Conclusions Research in this field demonstrates high activity and diversity.Studies on the associations of oral microbiota with gut microbiota,IBD,and diges-tive system tumors(particularly esophageal,gastric,pancreatic,and colorectal cancers)remain prominent.Future studies should prioritize elucidating underlying mechanisms and innovating in biomarker discovery and application.However,insufficient collaboration and resource-sharing among institutions currently hinder pro-gress in this field.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

ObjectiveTo establish fingerprint profiles and a quantitative determination method for Lycii Cortex， providing a scientific basis for the formulation of quality standards for Lycii Cortex and its roasted products. MethodsHigh performance liquid chromatography（HPLC） was developed for the quantitative method for determining kukoamine B in Lycii Cortex and its roasted products on an Alphasil XD-C₁₈ CH column（4.6 mm×250 mm， 5 μm）. HPLC fingerprint profiles were established for 10 batches of Lycii Cortex and its roasted products， and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the common peaks based on reference standards， literature and MS information. Quality evaluation indicators included yield of decoction pieces， appearance properties， content of kukoamine B， and fingerprint profiles. The temperature and time of the roasting process were investigated to select the optimal preparation process， which was then verified. Additionally， chemical pattern recognition was combined to assess the differences in the chemical composition of Lycii Cortex before and after roasting， as well as among samples from different origins. ResultsQuantitative analysis indicated that the contents of kukoamine B in Lycii Cortex and its roasted products were 0.35%-5.51% and 0.24%-4.15%， respectively. The transfer rate of kukoamine B was 58.6%-78.9% after roasting. The fingerprint profile analysis demonstrated that the method established in this study effectively separated kukoamine B from other components in the samples and distinctly differentiated it from its impurity peak， cis-N-caffeoylputrescine. The HPLC fingerprint profiles of Lycii Cortex and its roasted products showed high similarity（all above 0.95）， with 7 common peaks identified and five common components， including kukoamine B， cis-N-caffeoylputrescine， N-coumaroyl tyramine， feruloyltyramine， and glucosyringic acid， confirmed. Process optimization confirmed that baking at 110 ℃ for 20 min was a stable and feasible method for roasting Lycii Cortex. Principal component analysis and cluster analysis showed that there was little difference in the chemical composition between raw and roasted Lycii Cortex， but the quality of Lycii Cortex from different origins differed greatly. ConclusionThis study successfully established the fingerprint profiles and a quantitative method for the effective component kukoamine B in Lycii Cortex and roasted Lycii Cortex. The qualitative and quantitative analyses clarified that the impact of the roasting process on the chemical composition of Lycii Cortex was less significant than the variations due to its geographical origin. The findings of this study offer a reference for the development of quality evaluation methods and the establishment of quality standards for Lycii Cortex and its processed products.