Cardiac arrest is a major health event that poses a major threat to human life and health.Post-cardiac arrest brain injury is the main adverse prognostic factor and cause of death in patients who experience cardiac arrest.Currently,the therapeutic methods and effects are limited.In recent years,with the in-depth research on microbiota-gut-brain communication,it has been found that intestinal microbiota and their metabolites may play a role in the regulation of neuroinflammation in post-cardiac arrest brain injury.Short-chain fatty acids are the key substances in microbiota-gut-brain communication,and the mechanism involves immune,endocrine and neuroregulatory pathways.Supplementation of short-chain fatty acid-producing bacteria or short-chain fatty acids can improve intestinal flora disorder and reduce neuroinflammation after cardiopulmonary resuscitation.As a key mediator in microbial-gut-brain communication,short-chain fatty acids have great potential for the treatment of brain injury after cardiac arrest.This review explores the role and regulatory mechanism of microbiota-gut-brain communication in the neuroinflammation of brain injury after cardiopulmonary resuscitation through immune,endocrine and neuro-regulatory pathways,providing a new idea for the treatment of post-cardiac arrest brain injury.

Childhood primary renal tubular diseases are chronic kidney diseases characterized by impaired renal tubular reabsorption. Primary renal tubular disease has diverse clinical manifestations and lacks of specificity. Laboratory tests are limited，making it prone to missed diagnosis and misdiagnosis. Based on the current knowledge of renal tubular diseases，authors propose early warning signals of renal tubular diseases such as family history of primary tubular diseases，unexplained polyhydramnios during pregnancy，polydipsia，polyuria，delayed growth and development or rickets，decreased muscle strength and tone，unexplained electrolyte disturbance，hyperuricemia，acid-base disturbance，positive urine sugar test，renal tubular proteinuria，urinary imaging examination suggesting kidney stones，calcium deposition，renal cysts and early onset of eye，ear，joint and neuron injury.Meanwhile，some universal management strategies for primary renal tubular disease are proposed，emphasizing the importance of multidisciplinary collaboration，genetic testing and individualized intervention to improve the long-term prognosis of childhood primary renal tubular diseases.

Objective To explore the protective effect and possible mechanism of modified Shenqi Dihuang Decoction on podocytes in db/db mice based on ROS/NLRP3/GSDMD signaling pathway.Methods Fifty 8-week-old male db/db mice(SPF grade)were randomly divided into the model group,losartan group and TCM low-,medium-and high-dosage groups,with 10 mice in each group.Ten heterozygous db/m mice served as the blank group.Interventions were administered respectively for 12 weeks.The body mass,random blood glucose,serum creatinine,blood urea nitrogen and 24 h urinary protein content were detected,HE,PAS,PASM,Masson and Sirius red staining was used to observe the morphology of renal tissue,transmission electron microscopy was used to observe the ultrastructure of renal tissue,fluorescent probes were used to observe the release of ROS in renal tissue,immunofluorescence staining was used to detect the expression of Nephrin,NLRP3,Cleaved Caspase-1 and GSDMD-N in renal tissue,and Western blot was used to detect the expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18,Nephrin,Podocin,PODXL,WT-1 and Desmin proteins.Results Compared with the blank group,the body mass and random blood glucose of the model group mice significantly increased(P<0.05),and the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein were significantly increased(P<0.05);glomerular hypertrophy,dilation of renal glomeruli and tubules,thickening of basement membrane,matrix proliferation in mesangial area,abnormal deposition of collagen fibers in renal interstitium,accompanied by damage to renal tubular epithelial structure and focal glomerulosclerosis,significant increase in type Ⅰ collagen deposition,extensive fusion of podocyte processes,and scattered electron dense material in the basement membrane or subepithelial layer;the ROS content in renal tissue significantly increased(P<0.05),and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin significantly increased(P<0.05),the protein expression of Nephrin,Podocin,PODXL and WT1 significantly decreased(P<0.05).Compared with the model group,the body mass and random blood glucose of mice in each dosage of TCM group were relatively stable,the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein decreased;the pathological damage to renal tissue was reduced,the ultrastructure of podocytes was improved,and the density of podocytes increased;the ROS content decreased,and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin decreased,while the protein expression of Nephrin,Podocin,WT1 and PODXL increased.With the dosage of modified Shenqi Dihuang Decoction increased,the improvement effect gradually strengthened,and the differences in TCM high-dose group was statistically significant(P<0.05).Conclusion Modified Shenqi Dihuang Decoction can protects podocytes in db/db mice,potentially by modulating the ROS/NLRP3/GSDMD signaling pathway.

Objective To investigate the association between single nucleotide polymorphisms(SNP)rs57095329 and rs6864584 of miR-146a gene and cervical intraepithelial neoplasia(CIN).Methods A total of 96 patients diagnosed with CIN were randomly collected as the CIN group,and 225 healthy individuals examined during the same period were selected as the control group using SPSS software.Genotyping of the above SNP loci was performed using the TaqMan probe method,and their correlation with CIN was analyzed.Results The allele and genotype distribution of rs57095329 showed a statistically significant differences compared to the control group,with the frequency of the allele A in the CIN group significantly lower than that in the control group(P<0.001;OR=0.48,95%CI:0.32～0.70).In the dominant model,individuals carrying the G allele(A/G-G/G)had a significantly increased risk of CIN(P<0.001;OR=2.67,95%CI:1.64～4.37).In contrast,no correlation was found between the rs6864584 and the risk of CIN.Conclusion The A allele of the miR-146a gene at the rs57095329 locus may be a protective factor for CIN.

Objective To investigate the effects of isoflurane anesthesia on cognitive function and the hippocampal nerve growth factor(NGF)and tyrosine receptor kinase A(TrkA)signaling pathway in Alzheimer's disease(AD)mice,while explore the role of G protein inhibitory α subunit 1/3(Gαi1/3)in this pathway.Methods Twelve wide-type mice and 48 APP/PS1(AD)mice(all males)were respectively assigned into a control group and 4 experimental groups,including AD,AD+postoperative cognitive dysfunction(POCD)group,empty adenovirus group,and Gαi1/3 overexpression group,with 12 mice in each group.Morris water maze and novel object recognition tests were conducted to assess the learning and memory function of each group;Western blotting was applied to detect the expression of amyloid P-protein 1-42(Aβ1-42),IL-6,TNF-α,synaptotagmin-1,synapsin-1,and NGF,p-TrkA,Gαi1/3,and p-Gab1 in hippocampal tissues.Results Compared with the control group and AD group,the avoidance incubation period in the AD+POCD group is significantly extended from days 2 to 4(P＜0.05),enhanced expression of Aβ1-42,IL-6,and TNF-α(P＜0.05),and reduced expression of synaptotagmin-1,synapsin-1,NGF,p-TrkA,Gαi1/3,and p-Gab1(P＜0.05).When compared with the AD+POCD group and the empty adenovirus group,the avoidance latency in the Gαi1/3 overexpression group was significantly shorted on days 2 to 4(P＜0.05),down-regulation of Aβ1-42(2.00±0.39 vs 3.38±0.38),IL-6(1.65±0.37 vs 3.36±0.39),and TNF-α(1.58±0.30 vs 2.90±0.31,P＜0.05),and up-regulation of synaptotagmin-1,synapsin-1,Gαi1/3,and p-Gab1(P＜0.05).Conclusion Isoflurane anesthesia can exacerbate POCD in AD mice,and overexpression of Gαi1/3 can improve cognitive function by activating the phosphorylation of Gab1.

Objective To investigate the effects of Yitangkang on renal ectopic lipid deposition and the PPAR-α/PGC-1α signaling pathway in db/db mice;To explore its mechanism in improving renal injury.Methods Totally 30 db/db mice were divided into model group,Yitangkang group and losartan potassium group(10 mice in each group)using a random number table method.An additional 10 db/m mice were assigned as the blank group.The mice received corresponding interventions for 8 weeks.Body mass,fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),and 24-hour urinary protein content were measured,renal morphology and injury were observed using HE,PAS and Masson staining,lipid deposition in renal tissue was observed by oil red O staining,renal ultrastructure was observed by transmission electron microscopy,immunofluorescence staining was used to detect the expressions of CPT1A and Nrf2 in renal tissue,RT-qPCR was performed to assess the mRNA expressions of PPAR-α and PGC-1α,Western blot was used to detect the protein expressions of PPAR-α,CPT1A,PGC-1α,Nrf2,NRF1 and TFAM.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.05),and the contents of SCr,BUN and 24-hour urinary protein significantly increased(P<0.05);histopathology revealed glomerular hypertrophy,mesangial cell and matrix proliferation,thickened basement membrane,abnormal deposition of interstitial collagen fibers,increased lipid deposition in renal tissue,widespread foot process effacement,reduced foot process density(P<0.05),blurred mitochondrial outer membranes,swollen morphology,and indistinct cristae;mRNA expressions of PPAR-α and PGC-1α significantly decreased(P<0.05),and protein expressions of PPAR-α,CPT1A,PGC-1α,Nrf2,NRF1 and TFAM significantly decreased(P<0.05).Compared with the model group,the body mass and FBG of mice in Yitangkang group significantly decreased(P<0.05),but there was no significant difference in the above indexes in losartan potassium group(P>0.05);the contents of SCr,BUN and 24-hour urinary protein in Yitangkang group and losartan potassium group significantly decreased(P<0.05);the pathological damage and lipid deposition of renal tissue was alleviated,the ultrastructure of podocytes was improved,and the density of podocytes significantly increased(P<0.05);the mRNA expressions of PPAR-α and PGC-1α in renal tissue increased,and the protein expressions of PPAR-α,CPT1A,PGC-1α,Nrf2,NRF1 and TFAM increased,with statistical significance(P<0.05).Conclusion Yitangkang can effectively alleviate renal injury in diabetic nephropathy mice.The mechanism may be related to the activation of PPAR-α/PGC-1α signaling pathway and the reduction of renal lipid deposition and mitochondrial biogenesis.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

ObjectiveThrough multimodal research methods including medication rule mining， network pharmacology， molecular docking and dynamics simulation， and in vivo animal experiments， this study aims to speculate and verify the core composition （Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma） and efficacy （Qi-invigorating and blood-activating） of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy （DCM）， investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets， and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats. MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database， and the "Analysis Method" module of the platform was applied to mine and summarize medication rules， thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， SwissTargetPrediction platform， GeneCards database， MetaScape database， CytoScape software， etc. Then， molecular docking was performed via the CB-Dock2 platform， and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally， in vivo animal experiments were carried out. Twenty-eight Sprague Dawley （SD） rats meeting the research criteria were divided into a normal group， a model group， a drug combination group （3.3 g·kg^-1）， and a Yitangkang group （20 g·kg^-1）. A type 2 diabetes mellitus （T2DM） rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin （STZ）， followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period， the traditional Chinese medicine （TCM） compound and drug combination were administered for prevention and treatment intervention. Meanwhile， changes in blood glucose， body weight， and heart index of each group were monitored. Cardiac function was assessed by echocardiography， and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin （HE） and Masson staining， and the expression of L-type calcium channel （CACNA1C）， calmodulin （CALM1）， calcium/calmodulin-dependent protein kinase Ⅱδ （CAMK2D）， and neuronal nitric oxide synthase （NOS1） proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot. ResultsIn 62 DCM prescriptions， Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen， heart， and lung， and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis， （Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma）-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination， 714 drug combination action targets， 2 702 disease targets， and 286 intersection targets. Protein-protein interaction （PPI） network predicted nine interaction component-targets （nine active ingredients and four calcium signaling pathway target genes）. Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re， 1cll-quercetin， 9blh-（6S）-6-（hydroxymethyl）-1，6-dimethyl-8，9-dihydro-7H-naphtho［8，7-g］benzofuran-10，11-dione， and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group， the model group showed significant changes in blood glucose， body weight， myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression levels of CACNA1C， CALM1， CAMK2D， and NOS1 proteins （P<0.05， P<0.01）. Compared with the model group， the Yitangkang group had a certain improvement effect on the above indexes （P<0.05， P<0.01）. Compared with the Yitangkang group， the drug combination group showed no significant difference in improving myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression of CACNA1C， CALM1， CAMK2D， and NOS1 proteins， except for blood glucose and body weight. ConclusionGinseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats， and their mechanism of action may be related to the regulation of the calcium signaling pathway.

This paper summarizes the clinical experience in applying jiao （角） medicine to treat diabetes mellitus from the perspective of qi， blood， and fluids. It is believed that impaired spleen transportation and transformation is the key pathomechanism of diabetes， leading to metabolic disturbances in qi， blood， and fluids， and resulting in a sequential pathological progression of "qi → thick fluids → thin fluids → blood". At the qi level， the disease is mainly characterized by spleen qi deficiency and stagnation， and is commonly treated with Hongshen （Panax Ginseng）， Huangqi （Astragalus Mongholicus）， and Baizhu （Atractylodes Macrocephala） to tonify the spleen and regulate qi. At the thick fluids level， the condition manifests as abdominal distension， internal heat， and turbid pathogens， requiring Zexie （Alisma Orientale）， Huanglian （Coptis Chinensis）， and Dahuang （Rheum Palmatum） to clear the spleen and drain turbidity. At the thin fluids level， with qi and yin deficiency and predominant yin damage， Gegen （Pueraria Lobata）， Wuweizi （Schisandra Chinensis）， and Maidong （Ophiopogon Japonicus） are used to nourish yin and generate fluids. At the blood level， where vascular damage is predominant， Shuizhifen （Whitmania Pigra Powder）， Danshen （Salvia Miltiorrhiza）， and Sanqifen （Panax Notoginseng Powder） are applied to activate blood circulation， resolve stasis， and unblock the channels. Clinicians may flexibly select appropriate jiao medicine based on the specific pathological layer affected in each patient.

The dysfunction of qi, blood, and fluid underlies the pathology of diabetes mellitus. The symptoms, signs, and physical and chemical indexes of diabetes mellitus patients reflect the duration, degree, primary and secondary pathological state of the abnormal metabolism of qi, blood, and fluid. It is necessary to construct a three-dimensional syndrome differentiation system of diabetes mellitus based on spatial and temporal dimensions. According to the four stages of depression, heat, deficiency, and damage, the location of the disease can be locked into qi, ying, and blood levels. The process reflects the pathological trend of the abnormal metabolism of qi, blood, and fluid: qi depression (prodromal stage: asymptomatic metabolic disorder/early stage of qi level) → qi heat (initial stage: index stage/late stage of qi level) → deficiency of both qi and yin (middle stage: symptom stage of three more and one less/stage of ying level) → damage of zang-fu viscera and meridians (late stage: complication stage/stage of blood level). According to the time process, the treatment principles are proposed as follows: during the early stage of qi level, treatment should focus on strengthening the spleen to regulate qi flow, to prevent the accumulation of glucose; during the late stage of qi level, treatment should focus on clearing heat and resolving turbidity, to remove the stagnated heat caused by glucose; during the stage of ying level, treatment should focus on benefiting qi and nourishing yin, to improve the symptoms about deficiency of both qi and yin; during the stage of blood level, treatment should focus on promoting blood circulation and removing blood stasis, to remove the complication. According to the etiology and pathogenesis of diabetes mellitus, the sequential treatment strategy is thus proposed, which is strengthening the spleen to regulate qi flow, clearing heat and resolving turbidity, benefiting qi and nourishing yin, and promoting blood circulation and removing blood stasis. The compound prescriptions such as Houpo Sanwu Decoction, Baihu Jia Renshen Decoction, Danggui Liuhuang Decoction, and Taohong Siwu Decoction are used with modification in the stage-based treatment.