ObjectiveTo investigate the effect and mechanism of modified Sini San in ameliorating intestinal mucosal barrier by observing its effects on short chain fatty acids （SCFAs） and high mobility group protein B1 （HMGB1）/receptor of advanced glycation end products （RAGE） signaling pathways in chronic stress rats. MethodsThe 50 male SD rats were randomly divided into control group，model group，low-dose modified Sini San group （7.34 g·kg^-1·d^-1），high-dose modified Sini San group （14.68 g·kg^-1·d^-1），and Fructo-oligosaccharides group （3.15 g·kg^-1·d^-1），with 10 rats in each group. Except for the control group，all other groups were subjected to chronic unpredictable stress/social isolation to create a chronic stress model for 6 weeks. After 4 weeks of modeling，each treatment group was given corresponding drugs by gavage for 2 weeks while modeling. The control group and model group were given the same volume of physiological saline. The effects of Modified Sini San on behaviors，body weight，Bristol score in feces and fecal moisture content in chronic stress rats were observed. Hematoxylin and eosin （HE） staining was used to observe the pathological changes in the cecum. The content of SCFAs in the cecal contents of rats were detected by Gas chromatography-mass spectrometry （GC-MS）. Immunohistochemistry and Western blot were used to detect the expression of HMGB1/RAGE pathway related proteins in cecal tissue. The levels of ZO-1，Occludin，and Claudin-1 in the cecal tissue were detected by enzyme linked immunosorbent assay （ELISA）. ResultsCompared with the model group，the sucrose preference rate，total distance traveled and the number of grid crossings in the open field test of rats in the low-dose modified Sini San group were obviously increased （P<0.05， P<0.01），and the immobility time in the open field test and the immobility time in the forced swimming test of rats in the low-dose and high-dose modified Sini San groups were obviously reduced （P<0.05， P<0.01）. Meanwhile，the Bristol score and fecal moisture content of rats in the low and high dose groups of modified Sini San were obviously increased （P<0.05）. The low-dose group of modified Sini San had intact mucosal layer structure in the cecal tissue and reduced infiltration of inflammatory cells. The content of SCFAs in the cecal contents increased，with a obviously increase in the content of acetic acid，propionic acid，butyric acid，and isovaleric acid （P<0.05， P<0.01） and the expression levels of HMGB1，RAGE，Toll-like receptor 2（TLR2），Toll-like receptor 4（TLR4），tumor necrosis factor-α（TNF-α），and nuclear factor kappa-B p65（NF-κB p65） proteins in cecal tissue were significantly decreased （P<0.05， P<0.01） in low-dose group of modified Sini San. Meanwhile，the contents of ZO-1，Occludin，and Claudin-1 in the cecal tissue were obviously increased （P<0.01） in low-dose group of modified Sini San. ConclusionModified Sini San can improve the function of intestinal mucosal barrier in chronic stress rats by increasing the content of SCFAs in the intestine and inhibiting the HMGB1/RAGE pathway.

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

ObjectiveUltra performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS） coupled with network pharmacology and molecular docking was utilized to explore the efficacy and mechanism of action of Ermiao Situ decoction on rats with damp-heat eczema. MethodsA rat model of damp-heat eczema was established by artificial climate chamber intervention combined with sensitization induction by dinitrochlorobenzene （DNCB）， and it was randomly divided into the normal group， the model group， the medium- and high-dose groups of Ermiao Situ decoction （3.40 g·kg^-1 and 6.80 g·kg^-1）， and the prednisone acetate group （2.51 mg·kg^-1）， with eight rats in each group， totalling 46 rats， of which six rats were tested with the drug-containing serum. The chemical analysis of drug-containing serum from rats was carried out by UPLC-Q-TOF-MS/MS， combined with network pharmacology for the prediction of key components， core targets， and signaling pathways， and molecular docking experiments were performed by CB-Dock2 online website. The pharmacological effects of Ermiao Situ decoction in the treatment of damp-heat eczema were investigated by epitaxial indexes combined with the pathologic tissue staining method. The serum levels of gastrin （GAS）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured by enzyme-linked immunosorbent assay （ELISA）. Interleukin-6 （IL-6）， Janus kinase 1 （JAK1）， phosphorylated （p）-JAK1， signal transduction and activation of transcription factor 3 （STAT3）， and p-STAT3 protein expression level was determined by Western bolt. ResultsA total of 19 active ingredients were detected in drug-containing serum samples of rats， which were predicted to act on 198 targets for the treatment of damp-heat eczema， among which the key ingredients included rhodopsin， huangpai alkaloids， and quercetin， and the main core targets included STAT3， tumor necrosis factor （TNF）， and IL-6， which were mainly involved in the cancer signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase （Akt） signaling pathway， T helper 17 （Th17） cell differentiation signaling pathway， and JAK/STAT signaling pathway. The molecular docking results suggested that the key components had strong binding activities with the core targets IL-6， JAK1， and STAT3 in the JAK/STAT signaling pathway. The results of animal experiments showed that compared with those in the normal group， rats in the model group were depressed. They had loose hair， loose stools， epidermal oozing， vesiculation， and generation of thick scabs in the form of scales， decreased body weight， increased anus temperature and water intake， and increased indexes of the spleen， thymus gland， and stomach （P<0.05， P<0.01）， and the lesion tissue could be seen to be hyperkeratotic， with the aggregation of inflammatory cells and nonsignificant separation of epidermis and dermis. The gastric mucosa was thinned， deficient， and structurally disorganized， and obvious inflammatory cell aggregation was seen. The levels of GAS， IL-4， and IL-13 in serum were significantly reduced （P<0.05， P<0.01）， and the protein expression levels of IL-6， JAK1， p-JAK1， and p-STAT3 in the lesion tissue were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， rats in each administration group had stable mental states， formed feces， a clean perianal area， and basically normal epidermis. Only a small amount of scaly scabs existed， and the rats had body weight increased， with decreased anal temperature and water intake， as well as decreased spleen， thymus， and gastric indexes （P<0.05， P<0.01）. Epidermal thickness was decreased， and epidermal and dermal separation boundaries were obvious， but hyperkeratotic and accumulation of inflammatory cells could still be seen. The thickness of gastric mucosa increased， and the structure was restored to varying degrees. The levels of GAS， IL-4， and IL-13 content in the serum of rats were increased to varying degrees， and the protein expression levels of IL-6， JAK1， p-JAK1， and p-STAT3 in the dermal lesion tissue were significantly decreased （P<0.05， P<0.01）. ConclusionErmiao Situ decoction may exert therapeutic effects on rats with damp-heat eczema by modulating the JAK/STAT signaling pathway.

OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.

Inguinal hernia is a common general surgical non-oncological condition,with more than 20 million inguinal hernia surgeries performed annually worldwide.Surgery is the only treatment for inguinal hernias in adults due to the lack of spontaneous healing and ineffective pharmacological treatment,as well as the risk of life-threatening intestinal necrosis due to herniorrhaphy.The incidence of inguinal hernia is on the rise,and there may be an association between its pathogenesis and the mechanism of sarcopenia,as well as the adverse effects of sarcopenia on various postoperative conditions.This paper aims to investigate the relationship between the recognition,diagnosis,treatment,pathogenesis,early postoperative clinical recovery and recurrence of sarcopenia in patients with inguinal hernia.

Through studying Chen Yiren's works,this paper summarizes Chen Yiren's academic thought of diligently seeking and learning,thinking about the purpose of the classics,exploring the essence of the theory,and studying the prescriptions and techniques,and expounds Chen Yiren's experience of"learning,studying,distinguishing,and applying"Treatise on Cold Damage.Professor Chen Yiren advocates the combined theory of external and internal injuries,the"six meridians regulating all diseases"theory,and"bad dis-eases being difficult and complicated diseases"theory.His thought on studying is reflected in the following four aspects:learn,dili-gently seeking and learning,and teaching people the law,citing evidence from various schools,distinguishing syndromes and seeking causes,connecting with clinical practice,and summarizing the three methods of selecting prescriptions;research,thinking about the purpose of the classics and explaining the key points,summarizing the five major characteristics of Treatise on Cold Damage of"differ-entiation,change,strictness,flexibility,and simplicity",explaining that Yangming disease has no distinction between meridians and viscera,and emphasizing the combination of pulse and syndromes;distinguish,exploring the principles,distinguishing doubts and re-solving confusion,revealing the rules of diagnosis and treatment of bad diseases,showing people the"living"method,discussing the prescriptions and syndromes of Jueyin disease,and focusing on applying the ancient to the present;apply,studying the prescriptions and techniques carefully and differentiating flexibly,explaining that the six meridians regulates hundreds of diseases,distinguishing complex and difficult diseases and syndromes,clarifying the complications and suspected syndromes,using the differentiation method flexibly,and opening up ideas for the use of classic prescriptions.In addition,Chen Yiren emphasizes the important position of the Treatise on Cold Damage course in TCM education and talent training,which should be strengthened during education and teaching as well as curriculum construction,making great contributions to the inheritance and development of Treatise on Cold Damage.

Inguinal hernia is a common general surgical non-oncological condition,with more than 20 million inguinal hernia surgeries performed annually worldwide.Surgery is the only treatment for inguinal hernias in adults due to the lack of spontaneous healing and ineffective pharmacological treatment,as well as the risk of life-threatening intestinal necrosis due to herniorrhaphy.The incidence of inguinal hernia is on the rise,and there may be an association between its pathogenesis and the mechanism of sarcopenia,as well as the adverse effects of sarcopenia on various postoperative conditions.This paper aims to investigate the relationship between the recognition,diagnosis,treatment,pathogenesis,early postoperative clinical recovery and recurrence of sarcopenia in patients with inguinal hernia.

Through studying Chen Yiren's works,this paper summarizes Chen Yiren's academic thought of diligently seeking and learning,thinking about the purpose of the classics,exploring the essence of the theory,and studying the prescriptions and techniques,and expounds Chen Yiren's experience of"learning,studying,distinguishing,and applying"Treatise on Cold Damage.Professor Chen Yiren advocates the combined theory of external and internal injuries,the"six meridians regulating all diseases"theory,and"bad dis-eases being difficult and complicated diseases"theory.His thought on studying is reflected in the following four aspects:learn,dili-gently seeking and learning,and teaching people the law,citing evidence from various schools,distinguishing syndromes and seeking causes,connecting with clinical practice,and summarizing the three methods of selecting prescriptions;research,thinking about the purpose of the classics and explaining the key points,summarizing the five major characteristics of Treatise on Cold Damage of"differ-entiation,change,strictness,flexibility,and simplicity",explaining that Yangming disease has no distinction between meridians and viscera,and emphasizing the combination of pulse and syndromes;distinguish,exploring the principles,distinguishing doubts and re-solving confusion,revealing the rules of diagnosis and treatment of bad diseases,showing people the"living"method,discussing the prescriptions and syndromes of Jueyin disease,and focusing on applying the ancient to the present;apply,studying the prescriptions and techniques carefully and differentiating flexibly,explaining that the six meridians regulates hundreds of diseases,distinguishing complex and difficult diseases and syndromes,clarifying the complications and suspected syndromes,using the differentiation method flexibly,and opening up ideas for the use of classic prescriptions.In addition,Chen Yiren emphasizes the important position of the Treatise on Cold Damage course in TCM education and talent training,which should be strengthened during education and teaching as well as curriculum construction,making great contributions to the inheritance and development of Treatise on Cold Damage.

Objective:To reduce peri-mitral atrial flutter/tachycardia(AFL/AT), this study modified the ablation method of the mitral isthmus(MI) by adopting bipolar radiofrequency ablation (RFA) combined with "cut-and-sew" technique.Methods:This was a clinical retrospective study, involving a total of 138 consecutive patients with AF who underwent a mitral valve surgery and concomitant maze Ⅳ procedure. According to methods of MI linear lesion, patients were divided into the modified group and the RFA group. The primary end points are maintenance of sinus rhythm (SR) rate and the incidence of AFL/AT.Results:During the perioperative period, one patient in the modified group died of suspected cardiogenic shock and septic shock. Follow up for two years, no deaths or stroke events occurred. The proportion of 6-, 12-, and 24-month maintenance of SR off class Ⅰ/Ⅲ antiarrhythmic drugs after surgery were 91.0%, 89.7%, and 88.5% in the modified group and 89.7%, 84.5%, and 81.0% in the RF group, respectively ( P>0.05). The incidence of postoperative AFL/AT was 5.1% in the modified group and 15.3% in the RF group ( P=0.044). The healthcare facility use expense in the RF group was 1.5 times that in the modified group. Early recurrence of AF was an independent risk factor for AF recurrence. Conclusion:In the mitral valve surgery and concomitant maze Ⅳ procedure, the modified method of bipolar RF ablation combined with "cut-and-sew" technique for the MI line is safe and feasible. Its incidence of postoperative AFL/AT is lower than that of the RF method, which reduces existing medical costs and could be accepted by more patients and regions.

This article summarized the clinical experience of MEI Guoqiang in treating lung cancer of phlegm-heat obstructed in the lung syndrome with modified Xiaoxianxiong Decoction （小陷胸汤）. It is believed that the key pathogenesis of lung cancer with phlegm-heat obstructed in the lung syndrome is the phlegm-heat toxin accumulation. According to the different pathogenic effects of qi stagnation， blood stasis， pathogenic toxin， phlegm-damp， qi deficiency， yin deficiency in the occurrence and development of the disease， it is advocated to clear heat and resolve phlegm， and additionally the methods of diffusing the lung and relieving cough， resolving toxins and dissipating masses， rectifying qi and activating blood， dispelling dampness， supplementing and boosting qi and yin are used if necessary. Multiple methods are used together and flexibly matched. In clinical practice， Xiaoxian-xiong Decoction with the function of clearing heat and relieving phlegm is recommended as the basic formula for further modification. For patients with mild lung symptoms， modified Xiaoxianxiong Decoction is commonly used， while for those with obvious symptoms， self-made Maxing Xianxiong Decoction（麻杏陷胸汤） in modifications is suggested. For patients with Shaoyang （少阳） diseases， modified Chaihu Xianxiong Decoction （柴胡陷胸汤） is often used.