This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.

Objective:To investigate the clinical effect of free anterolateral thigh myocutaneous flap combined with oral repair membrane in the reconstruction of nasal mucosa defect after maxillary malignant tumor surgery. Methods:A total of 12 patients with maxillary gingival squamous cell carcinoma and maxillary sinus cancer who had been treated in Department of Oral and Maxillofacial Surgery, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, were selected from November 2020 to November 2023. Free anterolateral thigh musculocutaneous flap transplantation combined with oral repair membrane were used in all patients. Meanwhile, maxillary soft and hard tissue defects and nasal mucosa defects left after tumor operation were repaired and reconstructed. The clinical effect was evaluated after 6-12 months follow-up. Results:Subtotal maxillary resection was performed in 1 case, total maxillary resection in 9 cases and extended maxillary resection in 2 cases. The musculocutaneous flaps of all patients survived, the facial appearance was basically symmetrical, no obvious depression deformity, the swallowing and speech function recovered well, the mouth and nasal cavity were closed completely, the food could be eaten through the mouth, and the lower nasal passage was not blocked. Conclusion:The free anterolateral thigh musculoflap combined with oral repair membrane can be used to repair and reconstruct maxillary malignant tumor complicated with extensive maxillary tissue and nasal mucosa defect after operation, and the appearance and function can be recovered well after operation, which is a choice for maxillary malignant tumor complicated with nasal mucosa defect.
Humans ; Myocutaneous Flap ; Plastic Surgery Procedures/methods* ; Maxillary Neoplasms/surgery* ; Carcinoma, Squamous Cell/surgery* ; Male ; Middle Aged ; Female ; Nasal Mucosa/surgery* ; Maxilla/surgery* ; Thigh/surgery* ; Maxillary Sinus Neoplasms/surgery*

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective To discuss the risk of complications occurring after CT-guided percutaneous puncture pulmonary nodule biopsy and to establish its prediction model.Methods The clinical data and imaging materials of 180 patients with small pulmonary nodules,who received CT-guided percutaneous puncture pulmonary nodule biopsy at the Affiliated Hongqi Hospital of Mudanjiang Medical University of China from September 2018 to September 2023,were collected.Logistic regression analysis was used to screen out the independent risk factors for the occurrence of complications after CT-guided percutaneous puncture pulmonary nodule biopsy.Based on the results of logistic regression analysis,a risk prediction model was constructed.Results Of the 180 patients with small pulmonary nodules,42(23.33％)developed postoperative complications(complication group),including pneumothorax(n=18,10.00％),hemorrhage(n=20,11.11％),pleural reaction(n=2,1.11％),and fever(n=2,1.11％).No complication occurred in the remaining 138 patients(76.67％,non-complication group).The differences in the coexisting chronic obstructive pulmonary disease(COPD),nodule diameter,number of needle-passing across the pleura,residence time of puncture needle,and distance between lesion and chest wall between the two groups were statistically significant(all P＜0.05).Multivariate logistic regression analysis showed that coexisting COPD(OR=6.558,95％CI:1.225-9.228,P=0.028),nodule diameter＜8 mm(OR=5.387,95％CI:1.773-16.367,P=0.003),number of puncture needle-passing across the pleura ≥3(OR=2.044,95％CI:1.275-3.278,P=0.003),residence time of puncture needle＞10 min(OR=12.620,95％CI:2.687-18.557,P=0.001)and distance between lesion and chest wall ≥30 mm(OR=1.992,95％CI:1.049-2.217,P=0.035)were the independent risk factors for the occurrence of complications after CT-guided percutaneous puncture pulmonary nodule biopsy.The above determined risk factors were used as the predictors to construct a prediction model.Receiver operating characteristic(ROC)curve analysis indicated that the critical value of this model to predict the occurrence of complications after CT-guided percutaneous puncture pulmonary nodule biopsy was 35.736,the area under ROC curve(AUC)was 0.831(95％CI:0.788-0.913),the sensitivity was 73.7％(95％CI:0.705-0.882),and the specificity was 90.6％(95％CI:0.811-0.985).Conclusion The predictive risk model,which is established based on the indicators of coexisting COPD,nodule diameter＜8 mm,number of puncture needle-passing across the pleura ≥3,residence time of puncture needle＞10 min and distance between lesion and chest wall ≥30 mm,can well predict the occurrence of complications after CT-guided percutaneous puncture pulmonary nodule biopsy,and this model carries high clinical application value.

This paper summarized the experience of integrated acupuncture and moxibustion program in the treatment of bipolar disorder （BD）. The pathogenesis of BD is a complex of deficiency and excess， which is closely related to the liver failing to govern the free flow of qi， the spleen failing to transport， phlegm-heat harassing the heart spirit. The pathogenesis of depressive episode is mainly qi constraint， and the most common syndromes are liver qi constraint， liver constraint accompanied by spleen deficiency， phlegm and qi constraint， qi stagnation and blood stasis. The pathogenesis of manic episode is mainly fire-heat， and the most common syndromes are exuberant heat in yangming （阳明）， intense heart-liver fire， phlegm-fire disturbing heart， and exuberant fire damaging yin. BD can be treated by the integrated acupuncture and moxibustion program， in which acupuncture is used to soothe the liver and regulate the mind， and refined moxibustion is to unblock and replenish yang； collateral bloodletting and cupping is used to move qi and drain fire， and needle-embedding therapy can be used to consolidate the curative effect. These therapies together have the effects of soothing the liver and regulating qi， fortifying the spleen and dissolving phlegm， calming the heart and draining fire.

ObjectiveThis study aims to investigate the mechanism in which Celastrus orbiculatus extract （COE） affects the proliferation and differentiation of gastric organoids and the expression of Lgr5 and thus reverses the precancerous lesions of gastric cancer （PLGC） by regulating the leucine-rich repeat containing G protein-coupled receptor 5 （Lgr5）/Wingless （Wnt）/β-catenin signaling pathway based on a gastric organoid injury model. MethodGastric organoids were established based on stem cells of the mouse gastric gland. Gastric organoid injury models were constructed by treating gastric organoids with N-methyl-N'-nitro-N-nitrosoguanidine （MNNG， 0.02 mg·L^-1）. Gastric organoid injury models were randomly divided into normal group， model group （0.02 mg·L^-1 MNNG）， low， medium， and high dose （5， 10， 20 mg·L^-1） groups of COE， and Wnt inhibitor Dickkopf-related protein 1 （DKK1） （0.5 mg·L^-1） group， and they were treated with respective agents for 24 h. The number and volume of gastric organoids under different drug concentrations were observed under a microscope. The viability of the gastric organoid injury models was detected by Methyl thiazolyl tetrazolium （MTT） assay. The morphology and pathology of gastric organoids were observed using Hematoxylin and Eosin （HE） staining. The expression levels of Lgr5， Mucin2 （MUC2）， Mucin5AC （MUC5AC）， Mucin6 （MUC6）， Wnt， and β-catenin in gastric organoids under different drug concentrations were detected by Western blot （WB）. ResultCompared with the normal group， the number， volume， and activity of gastric organoids in the model group were decreased （P<0.01）， while the expressions of Lgr5， MUC2， Wnt， and β-catenin were significantly increased （P<0.01）. The expressions of MUC5AC and MUC6 were significantly decreased （P<0.01）. Compared with the model group， the number and volume of gastric organoids in the low， medium， and high dose groups of COE were all improved （P<0.01）， and the vitality of gastric organoids was significantly enhanced （P<0.01）. The effect was the most significant at a COE concentration of 20 mg·L^-1 （P<0.01）. The expressions of Lgr5 and MUC2 in the medium and high dose groups of COE were significantly reduced （P<0.01）， while the expression of MUC5AC and MUC6 were significantly increased in the low， medium， and high dose groups of COE （P<0.05， P<0.01）. Compared with the model group， Wnt inhibitors could promote the expression of MUC5AC and MUC6 in gastric organoids （P<0.05， P<0.01） and reduce the expression of MUC2， Wnt， and β-catenin. In addition， the combined use of COE at high concentrations and Wnt inhibitors could further promote this trend （P<0.01）. ConclusionCOE inhibits the Wnt/β-catenin pathway by inhibiting the expression of Lgr5， MUC2， Wnt， and β-catenin and promoting the expression of MUC5AC and MUC6， thus promoting the proliferation and differentiation of gastric organoids and reversing the PLGC process.

BACKGROUND:As a common clinical digestive disorder,irritable bowel syndrome becomes an advantageous disease of acupuncture treatment.However,the therapeutic mechanisms remain unclear.The methodological characteristics of omics coincide with the multi-target and multi-level characteristics of acupuncture,providing the possibility of revealing the principle of acupuncture in the treatment of the disease. OBJECTIVE:To investigate the pathogenesis of irritable bowel syndrome with diarrhea(IBS-D)and the effect of acupuncture at the combined points(selected based on etiologies and symptoms)on IBS-D based on proteomics. METHODS:Twelve 3-month-old male Sprague-Dawley rats were randomly divided into three groups:a control group,an IBS-D model group and an acupuncture group.The IBS-D rat models were prepared using the CAS method.After successful modeling,bilateral Zusanli points,bilateral Neiguan points and Guanyuan points were selected for acupuncture treatment in the acupuncture group,with a frequency of 120 times/minute,1 minute of acupuncture every 4 minutes,and 15 minutes of needle retention,at an interval of 1 day every 6 days,for 28 days in total.Rats in the normal control group and the model group were not given any intervention.The pressure threshold of rat abdominal retraction reflex was measured to evaluate the visceral hypersensitivity of rats.Proteomics analysis was performed using the liquid chromatography-tandem mass spectrometry-based platform.MaxQuant software,Perseus software and DAVID,KOBAS,VENNY,STRING online tools were used for the bioinformatics analysis of proteomic data.Visualization analysis was done using Cytoscape 3.7.1 software. RESULTS AND CONCLUSION:There were 47 differentially expressed proteins between the IBS-D model and control groups.Function analysis of differentially expressed proteins revealed that the pathogenic mechanism of IBS-D was associated with abnormal energy metabolism,the imbalance of colon motor function and increased visceral sensitivity.Important proteins related to IBS-D pathogenesis included Atp5a1,Atp5c1,Idh3b,Atp2a3,Pdhb,Ppp1ca and Mapk3.Sixty-one differentially expressed proteins were identified between the acupuncture group and IBS-D model group.Acupuncture at the combined points reversed the up-regulation of nine differentially expressed proteins and the down-regulation of nine differentially expressed proteins.Bioinformatics analysis revealed that acupuncture at the combined points for IBS-D could function via multi-targets and multi-pathways,reverse the damage of energy metabolism caused by IBS-D,and play a role against oxidative stress and inflammation,thereby relieving pain and regulating the imbalance of intestinal function.Important proteins related to acupuncture effects included Atp5a1,Atp5c1,Pdhb,Sars,Uqcrc2,Prdx2,Prdx4,Ppp1ca,Manf and Tmsb4x3.All these findings preliminarily illustrate the potential molecular mechanisms of IBS-D and the effect of acupuncture at the combined points in the treatment of IBS-D at the protein level,which provide a basis for the clinical application of acupuncture at the combined points.

Objective To investigate the protective effect of dexmedetomidine(DEX)against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells)and explore the underlying mechanism.Methods HK-2 cells were treated with erastin alone or in combination with different concentrations(2.5,5.0 and 10 μmol/L)of DEX,and the changes in cell viability were observed using CCK-8 assay.To explore the mechanism by which DEX inhibits erastin-induced ferroptosis,HK-2 cells were treated with erastin,erastin+10 μmol/L DEX,or erastin+10 μmol/L DEX+ML385(a Nrf2 inhibitor),after which the cell viability was assessed.The level of intracellular Fe2+was detected by cell ferrous iron colorimetric assay kit,and flow cytometry was performed to detect reactive oxygen species(ROS);MDA and reduced glutathione assay kits were used to detect the contents of MDA and GSH in the cells;The expressions of Nrf2,HO-1 and GPX4 proteins were detected by Western blotting.Results Erastin treatment significantly inhibited the viability of the cells,decreased GSH content,and increased intracellular levels of Fe2+,ROS and MDA.The combined treatment with 10 μmol/L DEX markedly increased the viability of the cells,increased GSH content,reduced the levels of Fe2+,ROS and MDA,and upregulated the protein expressions of Nrf2,HO-1 and GPX4 in the cells.The application of ML385 obviously blocked the protective effect of DEX and caused significant inhibition of the Nrf2/HO-1/GPX4 pathway,decreased the cell viability and GSH content,and increased the levels of Fe2+,ROS and MDA in HK-2 cells.Conclusion The protective effect of DEX against erastin-induced ferroptosis of HK-2 cells is probably mediated by activation of the Nrf2/HO-1/GPX4 pathway to inhibit oxidative stress.

Objective To investigate the protective effect of dexmedetomidine(DEX)against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells)and explore the underlying mechanism.Methods HK-2 cells were treated with erastin alone or in combination with different concentrations(2.5,5.0 and 10 μmol/L)of DEX,and the changes in cell viability were observed using CCK-8 assay.To explore the mechanism by which DEX inhibits erastin-induced ferroptosis,HK-2 cells were treated with erastin,erastin+10 μmol/L DEX,or erastin+10 μmol/L DEX+ML385(a Nrf2 inhibitor),after which the cell viability was assessed.The level of intracellular Fe2+was detected by cell ferrous iron colorimetric assay kit,and flow cytometry was performed to detect reactive oxygen species(ROS);MDA and reduced glutathione assay kits were used to detect the contents of MDA and GSH in the cells;The expressions of Nrf2,HO-1 and GPX4 proteins were detected by Western blotting.Results Erastin treatment significantly inhibited the viability of the cells,decreased GSH content,and increased intracellular levels of Fe2+,ROS and MDA.The combined treatment with 10 μmol/L DEX markedly increased the viability of the cells,increased GSH content,reduced the levels of Fe2+,ROS and MDA,and upregulated the protein expressions of Nrf2,HO-1 and GPX4 in the cells.The application of ML385 obviously blocked the protective effect of DEX and caused significant inhibition of the Nrf2/HO-1/GPX4 pathway,decreased the cell viability and GSH content,and increased the levels of Fe2+,ROS and MDA in HK-2 cells.Conclusion The protective effect of DEX against erastin-induced ferroptosis of HK-2 cells is probably mediated by activation of the Nrf2/HO-1/GPX4 pathway to inhibit oxidative stress.

Objective To evaluate the clinical effect of ultra-early endovascular treatment of ruptured tiny intracranial aneurysms(RTIAs).Methods A total of 35 patients with RTIAs who were treated with endovascular embolization within 24 hours after subarachnoid hemorrhage in our department from May 2017 to November 2022 were retrospectively analyzed.The basic clinical information,endovascular treatment results,clinical and imaging follow-up results were analyzed.Results The mean aneurysms maximum diameter is was(2.5±0.4)mm.Of these 35 patients with RTIAs,23 patients(65.7％)were treated with simple coil embolization,12 patients(34.3％)with stent assisted coiling.Immediate angiographic results showed that Raymond grade Ⅰ in 20 patients(57.1％),Ⅱ in 13(37.2％),Ⅲ in 2(5.7％).Perioperative complications occurred in 4 patients(11.4％),including Intraoperative aneurysm rupture in 2(5.7％),intra-stent thrombosis in 2(5.7％),massive cerebral infarction followed by decompressive craniectomy in 1,postoperative death in 1.Angiographic follow-up was performed in 24 patients(68.6％),recurrence in 1 patient receiving retreatment.Clinical follow-up were performed in 33 patients,The mRS of 0-2 were in 31 patients(93.9％).Conclusion Ultra-early endovascular treatment of RTIAs is effective and relatively safe,with favorable angiographic results and clinical outcomes at follow up.Intraoperative aneurysm rupture and thrombosis are the major perioperative complications.