ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome （IBS-C） by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， and substance P （SP）. MethodsA randomized controlled design was adopted， and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups （36 cases）.The observation group received Sanren Runchang formula granules twice daily， and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale （IBS-SSS）， IBS Quality of Life Scale （IBS-QOL）， and Bristol Stool Form Scale （BSFS） were used to assess clinical symptoms， and bowel movement frequency was recorded. The Self-Rating Anxiety Scale （SAS） and Self-Rating Depression Scale （SDS） were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT， VIP， and SP. ResultsThe total response rate in the observation group was 91.67% （33/36）， which was higher than that （77.78%， 28/36） in the control group （χ²=4.50， P<0.05）. After treatment， both groups showed increased defecation frequency and BSFS scores， decreased IBS-SSS total score， abdominal pain and bloating scores， IBS-QOL health anxiety， anxiety， food avoidance， and behavioral disorders scores， SAS and SDS scores， serum 5-HT and VIP levels， and increased SP levels （P<0.05， P<0.01）. Moreover， the observation group showed more significant changes in the indicators above than the control group （P<0.05， P<0.01）. The SP level showed no significant difference between the two groups. During the 4-week follow-up， the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group， and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients， with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP， suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However， its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Objective To discuss the possible etiology,pathogenesis,clinical features,diagnosis and treatment of epidermoid cysts of the jaw and to provide a reference for clinical diagnosis and treatment.Methods A case of an epi-dermoid cyst in the right mandible with retained deciduous teeth and succedaneous impacted teeth was reviewed and an-alyzed in combination with the relevant literature.Results A patient presented with a mass in the right mandible that had persisted for 1 month after being found at imaging examination.Tooth 83 was retained,and tooth 43 was unerupted.Swelling was characterized by no obvious tenderness,fluctuation,or table tennis sensation and was observed in the lin-gual alveoli of teeth 83,44,and 45.Imaging revealed a low-density shadow in the apex of teeth 83,44,45,and 46,approximately 1.9 cm × 2.6 cm × 1.6 cm in size,which wrapped around the dental crown of tooth 43.Preliminary diag-noses were as follows:right mandibular mass thought to be a dentigerous cyst;impacted tooth 43;and retained primary tooth 83.The mass in the right mandible was removed,and teeth 43 and 83 were extracted under intravenous and inha-lation anesthesia.During the operation,the mass was observed to have a thin cyst wall and contained bean-like residue.Histopathological examination indicated an epidermoid cyst in the right mandible.At the 1-week follow-up examination,the patient reported no discomfort,and the surgical area showed good recovery.According to the literature,epidermoid cysts are benign cysts originating from ectopic ectodermal tissue that can occur throughout the body but rarely in the oral cavity and are even extremely rarer in the jaw.Epidermoid cysts of the jaw,which have no specific clinical manifes-tations,can be confused with odontogenic cysts such as dentigerous cysts and odontogenic tumors.Dental pulp tests and other techniques can serve as a reference for clinicians.The diagnosis is confirmed via histopathology.Surgical removal is a common treatment,with a good prognosis and a low recurrence rate.Conclusion The principle of treatment for an epidermoid cyst of the jaw is similar to that for a jaw cyst.The prognosis is good when the cyst is removed completely.

Purpose: Radiation-induced dermatitis (RD) is a common side-effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs). Methods: Using EMRs, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic curve. Results: The incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an area under the receiver operating characteristic curve of .66. Conclusions The risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital.

ObjectiveTo investigate the value of MELD 3.0， MELD， and MELD-Na scores in assessing the 90-day prognosis of patients with acute-on-chronic liver failure （ACLF） through a comparative study. MethodsA retrospective analysis was performed for the clinical data of 605 patients with ACLF who were treated in Tianjin Third Central Hospital， The Fifth Medical Center of Chinese PLA General Hospital， and Beijing YouAn Hospital from November 2012 to June 2019， and according to the 90-day follow-up results after admission， they were divided into survival group with 392 patients and death group with 213 patients. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， net reclassification improvement （NRI）， integrated discrimination improvement （IDI）， and decision curve analysis （DCA） curve were used to investigate the value of MELD 3.0， MELD， and MELD-Na scores at baseline， day 3， week 1， and week 2 in predicting the prognosis of the disease. ResultsAt day 3 and week 1， MELD 3.0 score had an AUC of 0.775 and 0.808， respectively， with a better AUC than MELD score （P<0.05）. At day 3， week 1， and week 2， MELD 3.0 score showed an NRI of 0.125， 0.100， and 0.081， respectively， compared with MELD in predicting the prognosis of ACLF patients， as well as an NRI of 0.093， 0.140， and 0.204， respectively， compared with MELD-Na score in predicting prognosis. At baseline， day 3， week 1， and week 2， MELD 3.0 showed an IDI of 0.011， 0.025， 0.017， and 0.013， respectively， compared with MELD in predicting the prognosis of ACLF patients. At day 3 and week 2， MELD 3.0 showed an IDI of 0.027 and 0.038， respectively， compared with MELD-Na in predicting the prognosis of ACLF patients. All the above NRIs and IDIs were >0， indicating a positive improvement （all P<0.05）. DCA curves showed that MELD 3.0 was superior to MELD at day 3 and was significantly superior to MELD-Na at week 2. There was no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with different types， and there was also no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with the etiology of HBV infection， alcohol， or HBV infection combined with alcohol， while MELD 3.0 was superior to MELD for ACLF patients with other etiologies （P<0.05）. ConclusionMELD 3.0 score is better than MELD and MELD-Na scores in predicting the 90-day survival of patients with ACLF， but with limited superiority.

AIM: To explore which variables can predict the weight response to exenatide and to individualize specific therapies for patients with type 2 diabetes mellitus (T2DM) who need treatment with exenatide. METHODS: We performed a study among T2DM patients who were treated with exenatide twice daily for at least 12 months from January 2017 to December 2020. Data of the height, weight, body mass index (BMI) calculated, and HbA1c, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting serum insulin (FINS), postprandial serum insulin (PINS), blood lipids and concurrent diabetic medications at baseline, 3 months, 6 months and 12 months after exenatide initiation were collected. Patients were categorized into two cohorts based on weight loss ≥3%: responders and non-responders. The binary logistic regression analysis was used to identify the major variables of weight response to exenatide. RESULTS: The duration of diabetes in the responder group was shorter than that in patients in the non-responder group (P<0.05). For patients in the responder and non-responder groups, there was a significant decrease in weight, BMI, HbA1c, FPG, PPG, homeostasis model assessment of insulin resistance (HOMA-IR) and increase in homeostasis model assessment for beta cell function (HOMA-B) compared with the prarameters before treatment with exenatide (P<0.001). The baseline weight and baseline HbA1c were associated with weight loss after 6 months of treatment with exenatide (P<0.05). CONCLUSION: Baseline weight and HbA1c improvement were positively correlated with weight loss after 6 months of treatment with exenatide and the major predictors of weight response to exenatide.

Objective: To investigate the differences and clinical significance of circRNA expression profiles in oral leukoplakia (OLK) tissues and normal oral mucosal (NOM) tissues. Methods: High-throughput sequencing was used to detect differentially expressed circRNAs in 6 pairs of OLK and NOM tissues, and qRT-PCR was used to verify the expression of 10 circRNAs screened in 6 pairs of OLK and NOM tissues. The ring formation of circRNA was verified by RNase R digestion and Sanger sequencing, and the target circHLA-C was further verified by qRT-PCR in 20 pairs of OLK and NOM tissues. CircHLA-C was visualized using the UCSC genome browser (genome.ucsc.edu). The function of differentially expressed circRNAs was analyzed by GO and KEGG enrichment analyses. TargetScan and miRanda predicted the downstream miRNAs and mRNAs of the target circRNAs, and a ceRNA network related to the identified circRNAs was constructed in Cytoscape. Results: Sequencing analysis showed that 366 circRNAs were significantly differentially expressed in OLK tissues, including 65 upregulated and 301 downregulated circRNAs. After qRT-PCR verification, 7 of the 10 screened circRNAs were expressed consistent with the sequencing results. The upregulated circHLA-C was confirmed to be a real circRNA with back-splice junction sites by RNase R digestion and Sanger sequencing. Correlation analysis showed a positive correlation between circHLA-C and the degree of OLK dysplasia. ROC curve analysis suggested that circHLA-C had potential value in diagnosing OLK with high accuracy and specificity. Conclusion CircRNA was significantly abnormally expressed in OLK tissues, and the upregulation of circHLA-C may be related to the degree of OLK dysplasia, providing guiding value for the diagnosis of OLK in the future.

Objective:To assess the value of amide proton transfer weighted (APTw) imaging in the evaluation of pH changes in infarct core (IC) and ischemic penumbra (IP) in subacute cerebral infarction.Methods:The data of twenty-three subacute cerebral infarction patients with unilateral steno-occlusive disease of the middle cerebral artery (subacute infarction group) from April to November 2019 in the First Affiliated Hospital of Dalian Medical University were prospectively analyzed. Fifteen healthy volunteers were enrolled in this study as the control group. All subjects underwent conventional MRI, DWI, 3D-pseudo continuous arterial spin labeling (3D-pCASL) and APTw sequences. Based on DWI images, relative cerebral blood flow (rCBF) and APTw images to determine the region of IC, blood flow penumbra [cerebral blood flow(CBF)-DWI mismatch area, IP CBF] and metabolic penumbra (APTw-DWI mismatched area, IP APT). 3D ROIs were used to semi-automatically measure the APTw signals and the volume of IC and IP CBF of the patients in subacute infarction group. The comparison of APTw signals between the infarct side and the contralateral side in the subacute infarction group, the comparison of bilateral APTw signals in the control group, and the comparison of APTw signals in the IC and IP CBF regions were performed by paired-sample t test or Wilcoxon signed-rank test. The paired-sample t test or Mann-Whitney U test was used to compare the APTw signals between the two groups. The Friedman test was applied to compare the difference of volumes among IP CBF1.5, IP CBF2.5 and IP APT . Results:There was no significant difference of the APTw signals among the IC, the contralateral side in the subacute infarction group and the control group ( P>0.05). The APTw signals of IP CBF and IC of the infarction group were statistically different ( P<0.05). Compared with the contralateral side of IP CBF1.5 (3.7±1.7, -1.84±1.48, 5.57±2.75), the APTwmax (3.07±1.41, t=-3.012, P=0.006), APTw min [-1.30 (-1.74, -0.57), Z=-2.099, P=0.036], and APTwmax-min(4.51±2.58, t=-3.273, P=0.003) signals in the IP CBF1.5 were decreased ( P<0.05). Compared with the contralateral side of IP CBF2.5 [-1.53 (-2.80, -0.91), 5.31±2.61], the APTw min [-1.08 (-1.60, -0.49), Z=-2.616, P=0.009] and APTwmax-min (4.41±2.72, t=-3.228, P=0.004) signals in the IP CBF2.5 were decreased. The volumes of IP CBF1.5 [107.51(50.08, 138.61)mm 3], IP APT [99.00 (53.27, 121.335) mm 3] and IP CBF2.5 [89.91 (51.53, 139.87) mm 3] were successively reduced (χ2=7.913, P=0.019), and the volume of IP CBF2.5 was significantly smaller than that of IP CBF1.5 ( P=0.037). Conclusion:The acid-base metabolism in the IC of subacute cerebral infarction is not obvious, but the blood flow penumbra has local acid-base metabolism imbalance, and the range of metabolic penumbra coincides with the blood flow penumbra.

Objective:To explore the protective effect of α-lipoic acid (LA) on radiation damage of mice cochlear ribbon synapses.Methods:Mice were divided into five groups: control group, radiation 3 d group, radiation 3 d+ LA group, radiation 14 d group and radiation 14 d+ LA group. The radiation groups were irradiated with 16 Gy, the radiation+ LA groups were given LA once a day after radiation, the control group was given the same amount of normal saline. The auditory brainstem response (ABR) of mice were measured before irradiation and sacrifice. The number of ribbon synapses were observed with immunofluorescently labeled protein ctBP2. Western blot assay was performed to obtain the semi-quantitative expression levels of otoferlin and AP-2 protein.Results:Compared with the control group, the ABR threshold of radiation groups were significantly higher ( P<0.05) with the highest value at 14 d after irradiation ( P<0.05), and the ABR threshold of the radiation+ LA groups were significantly lower ( P<0.05). The ABR threshold shifts of 12 kHz, 24 kHz at 3 d and 14 d groups had no significant difference with 8 kHz threshold shift ( P>0.05). The 32 kHz threshold shift was significantly higher than 8 kHz threshold shift ( t=-2.38, -5.48, P<0.05). The number of ribbon synapses in the radiation groups was significantly lower than that of control group ( P<0.05), with the lowest value in the radiation 14 d group. LA treatment increased the ABR value significantly ( P<0.05). AP-2 and otoferlin protein levels were significantly reduced after irradiation, especially in the radiation 14 d groups, and they were increased by the LA treatment. Conclusions:LA has protective effect on the ribbon synapses of cochlear hair cells.