OBJECTIVE To study the effects of peripheral blood-derived exosomes （Exo） intervened by Naozhenning （NZN） on injury of neuron cells HT22 induced by microglia BV-2 cells. METHODS Wistar rats were selected to prepare peripheral blood- derived Exo intervened by NZN （66.83 g/kg）， referred to as NZN-Exo； peripheral blood-derived Exo intervened by normal saline and piracetam （PLXT， 1.62 g/kg） were prepared using the same method， denoted as KB-Exo and PLXT-Exo respectively， and all Exo were subsequently identified. Meanwhile， BV-2 cells were stimulated with 1 μg/mL lipopolysaccharide （LPS） to prepare LPS- stimulated supernatant， and non-LPS-stimulated supernatant was prepared following the same protocol. HT22 cells were divided into four groups: KB-Exo group （treated with non-LPS-stimulated supernatant+KB-Exo）， model group （treated with LPS-stimulated supernatant+KB-Exo）， PLXT-Exo group （treated with LPS-stimulated supernatant+PLXT-Exo）， and NZN-Exo group （treated with LPS-stimulated supernatant+NZN-Exo）， with the concentration of the corresponding Exo in all groups being 50 μg/mL. After 24 hours of culture， the proliferation of HT22 cells was detected by the CCK-8 assay and EdU assay； the apoptosis of HT22 cells was detected； the microstructure of HT22 cells was observed； the contents of interleukin-1β （IL-1β）， IL-10， nuclear factor-κB （NF- κB）， and tumor necrosis factor-α （TNF-α） in HT22 cells were measured， as well as the expression levels of TNF-α， NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， Caspase-1， B-cell lymphoma-2（ Bcl-2）， and Bcl-2-associated X protein （Bax）. RESULTS KB-Exo， PLXT-Exo and NZN-Exo were successfully prepared， and all Exo exhibited typical cup-shaped contours and membrane-enclosed characteristics. Compared with KB-Exo group， model group showed significantly decreased cell proliferation rates （detected by CCK-8 and EdU）， intracellular IL-10 levels， and Bcl-2 protein expression levels （P＜0.05）； while the cell apoptosis rate， intracellular levels of IL-1β， TNF-α， and NF-κB， as well as the expression levels of NLRP3， TNF-α， Caspase-1， and Bax proteins were significantly increased （P＜0.05）. Additionally， in the model group， the cells showed volume swelling， incomplete cell membrane， nucleolar rupture， significant swelling and deformation of mitochondria， and severe vacuolization. Compared with model group， the above quantitative indicators in the PLXT-Exo group and NZN-Exo group were significantly reversed （P＜0.05）， with large and round cell nuclei， intact nuclear membranes， and reduced mitochondrial vacuolization. CONCLUSIONS Peripheral blood-derived Exo intervened by naozhenning can alleviate the injury of neuronal cells HT22 by inhibiting inflammatory responses and cell apoptosis.

BACKGROUND: Endoscopic sphincterotomy (EST) is widely used to treat common bile duct stones (CBDS); however, long-term studies have revealed the increasing incidence of recurrent CBDS after EST. Loss of sphincter of Oddi function after EST was the main cause of recurrent CBDS. Reparation of the sphincter of Oddi is therefore crucial. This study aims to investigate the effectiveness and safety of endoclip papilloplasty (ECPP) for repairing the sphincter of Oddi and elucidate its mechanism. METHODS: Eight healthy Bama minipigs were randomly divided into the EST group and the ECPP group at a 1:1 ratio, and bile samples were collected before endoscopy and 6 months later. All minipigs underwent transabdominal biliary ultrasonography for the diagnosis of cholelithiasis 6 months after endoscopy. The biliary microbiota composition and alpha and beta diversity were analyzed by 16S ribosomal RNA gene sequencing. Differential metabolites were analyzed by bile acid metabolomics to explore the predictive indicators of cholelithiasis. RESULTS: Three minipigs were diagnosed with cholelithiasis in the EST group, while none in the ECPP group showed cholelithiasis. The biliary Firmicutes/Bacteroidota (F/B) ratio was increased after EST and decreased after ECPP. The Chao1 and observed species index significantly decreased 6 months after EST ( P  = 0.017 and 0.018, respectively); however, the biliary α-diversity was similar before and 6 months after ECPP. The β-diversity significantly differed in the EST group before and 6 months after EST, as well as in the ECPP group before and 6 months after ECPP (analysis of similarities [ANOSIM]: R  = 0.917, P  = 0.040; R  = 0.740, P  = 0.035; respectively). Glycolithocholic acid (GLCA) and taurolithocholic acid (TLCA) accumulated in bile 6 months after EST. CONCLUSIONS ECPP has less impact on the biliary microenvironment than EST and prevents duodenobiliary reflux by repairing the sphincter of Oddi. The bile levels of GLCA and TLCA may be used to predict the risk of cholelithiasis.
Animals ; Swine, Miniature ; Swine ; Cholelithiasis/prevention & control* ; Sphincterotomy, Endoscopic/methods* ; Sphincter of Oddi/surgery* ; Female ; Male

Objective To evaluate the value of modified percutaneous endoscopic gastrostomy(PEG)for patients with amyotrophic lateral sclerosis(ALS)and dysphagia.Methods From January 2018 to December 2023,47 patients with ALS were treated with modified PEG in our hospital.The surgery was performed under local anesthesia.The patients were placed in a semi-seated position,and the surgeon performed surgery with an ultra-fine endoscope through oral entrance to the stomach.Results The modified PEG were successfully completed in all the 47 cases.The operation time was5-20 min[mean,(10.3±1.7)min].The postoperative hospitalization lasted for2-8 d(mean,2.8 d).Postoperative complications occurred in6 cases(12.8%),including aspiration pneumonia in4 cases(8.5%)and incision infection in2 cases(4.3%).The body mass index was17.06±0.89 before PEG and 18.15±0.81 at 3 months after PEG,with significant difference(t=-10.373,P=0.000).Conclusion For ALS patients with dysphagia,modified PEG is feasible,which significantly improves nutritional status of patients.

Objective:A retrospective study was conducted to investigate the safety of Percutaneous Endoscopic Gastrostomy(PEG)in elderly patients with Amyotrophic Lateral Sclerosis(ALS)and to identify the factors influencing major complications.The aim is to establish a more robust foundation for optimizing both the procedure and its timing, thereby enhancing the evidence base for refining the surgical approach.Methods:We retrospectively collected clinical data from elderly ALS patients(≥60 years old)who underwent PEG at Peking University Third Hospital between January 2006 and January 2024.This dataset includes information on general health conditions, the progression of ALS, comorbidities, surgical details, and related complications.Additionally, we analyzed the postoperative complications experienced by the included patients, focusing specifically on the risk factors associated with aspiration pneumonia.Results:A total of 140 patients were included in the study, with a mean age of 68.2±5.9 years.Among these, 69 were male(49.3%)with a mean age of 68.4±6.5 years, and 71 were female(50.7%)with a mean age of 67.7±6.0 years.Successful outcomes were observed in 139 cases(99.3%).One case was not completed due to respiratory arrest caused by intraoperative aspiration.Postoperative complications occurred in 36 cases(25.7%), which included 9 cases of wound infection(6.4%), 1 case of abdominal infection(0.7%), 21 cases of aspiration pneumonia(15.0%), 1 case of local fistula leakage(0.7%), 2 cases of transient fever(1.4%), and 2 cases of death during hospitalization(1.4%).Both univariate and multivariate analyses indicated that an onset duration of ≤1 year( P=0.020)and a half-sitting position( P=0.022)significantly influenced the occurrence of aspiration pneumonia, acting as protective factors( β<0, OR<1). Conclusions:PEG is a safe method for providing enteral nutrition to elderly patients with ALS.While most complications associated with the procedure are mild and can be managed, Aspiration pneumonia remains a common and serious complication.However, early surgical intervention and the use of a semi-seated position during the procedure can help reduce the incidence of aspiration pneumonia.

Objective:To explore the surgical strategies and clinical efficacy of open partial nephrectomy in the treatment of renal angiomyolipoma (AML) with inferior vena cava tumor thrombus.Methods:A retrospective analysis was conducted on the clinical data of 5 patients with renal AML and inferior vena cava tumor thrombus who underwent partial nephrectomy at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to December 2022. There were 2 male and 3 female patients, with a median age of 37 years, ranged from 33 to 45 years. All patients were identified during routine physical examinations. Four patients presented with right-sided lesions, while one had a left-sided lesion. The diameter of the primary tumor within the kidney ranged from 3.0 to 7.0 cm, with a median diameter of 5.5 cm.The length of the tumor thrombus within the inferior vena cava ranged from 1.0 to 6.0 cm, with a median length of 1.5 cm. Among them, 2 patients underwent laparoscopic nephrectomy combined with extracorporeal workbench tumor resection and autologous kidney transplantation (the workbench surgery group), while 3 patients underwent open in-situ partial nephrectomy combined with removal of inferior vena cava tumor thrombus (the in-situ nephron-sparing surgery group). The surgical method of the workbench surgery group: The patients first underwent laparoscopic nephrectomy on the affected side combined with inferior vena cava tumor thrombus removal, then the incision was extended to remove the affected kidney, and table partial nephrectomy was performed. After completely removing the tumor and tumor thrombus within the affected kidney and renal vein, autologous kidney transplantation was performed in the iliac fossa. The surgical method of the in-situ kidney preservation surgery group: The affected kidney, renal artery and vein on the affected side, inferior vena cava, and contralateral renal vein were dissected and exposed. The distal end of the inferior vena cava, the contralateral renal vein, the proximal end of the inferior vena cava, and the renal artery on the affected side were blocked respectively. The venous wall was opened in the middle of the renal vein, and the tumor thrombus was gradually pulled out. According to the pre-marked tumor boundary, the tumor within the kidney was gradually removed by alternate blunt and sharp dissection combined with suction, and the wound surface was sutured layer by layer. The perioperative conditions, complications, and follow-up results of the patients were analyzed.Results:All 5 surgeries were successfully completed, with a median operation time of 100 to 450 minutes and a median operation time of 200 minutes. The intraoperative bleeding volume was 100 to 600 ml, with the median of 150 ml. In the in-situ nephron-sparing surgery group, the renal artery occlusion time was 28 to 41 minutes, and the median occlusion time was 34 minutes. All patients were discharged safely after surgery, and there were no serious perioperative complications. The postoperative pathology of all 5 patients was renal angiomyolipoma, without any epithelioid components. The patients were followed up for 12 to 90 months, with a median follow-up duration of 24 months. None of the 5 patients had tumor recurrence or metastasis, and no patient developed chronic kidney dysfunction during follow-ups.Conclusions:Renal AML with venous tumor thrombus is a challenging clinical problem. In situ open partial nephrectomy or the combined approach through the workbench and autologous kidney transplantation can effectively remove the tumor thrombus and maximize the protection of renal function. For cases of ① multiple or complex renal AML; ② complex vascular system structure within the renal sinus requiring precise anatomy; ③ renal AML with a previous history of hemorrhage, complex adhesions around, and difficult dissociation, table partial nephrectomy combined with inferior vena cava tumor thrombus removal and autologous kidney transplantation can be selected. For cases where the expected surgical operation is simple, in situ open partial nephrectomy can significantly shorten the operation time and reduce surgical trauma.

AIM:This study aims to investigate the sustained and stable drug release profile of the injectable hydrogel lidocaine(LDC)/betamethasone sodium phosphate hydrogel(BetP-Gel)and its effect on analgesic duration in a mouse model of acute incisional pain.METHODS:The drug-loaded hydrogel LDC/BetP-Gel was prepared through a sim-ple mixing process.Its physicochemical properties were characterized using electron microscopy,X-ray diffraction,Fouri-er-transform infrared spectroscopy,and rheological testing.In vivo gelation and injectability were evaluated through posi-tron emission tomography/computed tomography(PET-CT)imaging and pressure variation measurements.The in vitro drug release rate was determined using a direct release method,while the degradation rate was assessed using the residual weight method.A total of thirty BALB/c mice were randomly assigned to five groups:blank group,model group,4%LDC group,BetP-Gel group,and 4%LDC/BetP-Gel group.Pain behavior was assessed using the Up-Down method and Harg-reave's test.Biocompatibility was evaluated through HE staining,and the expression levels of inflammatory cytokines were measured via enzyme-linked immunosorbent assay(ELISA).RESULTS:The LDC/BetP-Gel hydrogel demonstrated ex-cellent drug encapsulation and sustained release properties.Behavioral assessments indicated that the LDC/BetP-Gel group exhibited significantly higher pain thresholds compared to the model group(P＜0.05),suggesting improved postop-erative pain relief.Furthermore,the LDC/BetP-Gel group showed a markedly prolonged analgesic effect compared to the LDC group(P＜0.05).HE staining confirmed the biocompatibility of the hydrogel.ELISA results revealed a significant re-duction in inflammatory cytokine levels in the LDC/BetP-Gel group 24 hours post-surgery(P＜0.05).CONCLUSION:The injectable hydrogel LDC/BetP-Gel possesses a dense and stable structure that enables effective drug loading and sus-tained release.Its ability to prolong anti-inflammatory and analgesic effects has been validated in a mouse model of acute incisional pain.

A microfluidic extracorporeal membrane oxygenator is an advanced extracorporeal life support device designed using microfluidic technology,capable of providing oxygenation support to patients with severe respiratory failure and other pulmonary diseases via extracorporeal circulation.Compared to conventional extracorporeal membrane oxygenators,it features a more superior biomimetic design,demonstrating potentials for improved therapeutic outcomes and reduced complications.This review summarizes the research progress of microfluidic extracorporeal membrane oxygenators in terms of hemodynamics,membrane materials,biocompatibility,gas exchange efficiency,and structural design.It analyzes how factors such as blood channel design,material selection and surface modification techniques impact the performance of microfluidic extracorporeal membrane oxygenators,such as biomimetic flow paths minimizing shear stress and endothelial cell linings significantly reducing thrombosis.Finally,the limitations of microfluidic extracorporeal membrane oxygenators are discussed,along with prospects for future development.Innovations are still needed in enhancing biocompatibility,portability,manufacturability,and cost reduction for microfluidic extracorporeal membrane oxygenators.

Objective Under the guidance of Zhuang medicine theory,this study aims to investigate the medicinal and compatibility rules of authentic medicinal pearls.Method This article focuses on the fourth national survey of traditional Chinese medicine resources—general survey of marine traditional Chinese medicine resources in Guangxi,led by Professor Lin Jiang's team from Guangxi University of Traditional Chinese Medicine and Guangxi Famous Traditional Chinese Medicine.The survey collected original prescriptions containing pearls,as well as data recorded in Zhuang medicine monographs containing pearls.The study integrated the efficacy,indications,pharmacology,and clinical research of pearl Zhuang medicine.Under the guidance of Zhuang medicine prescription compatibility theory,Zhuang medicine disease classification,and Zhuang medicine classification theory,this study explores the compatibility rules based on the data and functions of Zhuang medicine pearl formula.Result Zhuang medicine pearls taste sweet and salty,with a cold nature;It has the effects of activating the Qiao wu(brain),regulating Long lu(blood circulatory system)and Huo lu(nervous system),clearing heat and toxins,calming the mind,calming palpitations,relieving cough,promoting muscle growth,nourishing yin fluids,and Clearing eye mistiness;Indications:Nian nao nuo(Insomnia),Hen feng(Infantile Convulsions),Long lei(Epilepsy),Fright Palpitations,A rou tian(Diabetes),Huo yan ma(Sore throat),Bei ding(Deep-Rooted Boil),Bei nong(Sores and Ulcers),Redness and visual obstruction due to corneal opacity,Re Nong(Otitis media),Kou chuang(Oral ulcers),Da ning(Swelling and pain of eye).Based on the analysis of data on the formula of Zhuang medicine pearls,it was found that the topical use of Zhuang medicine pearls is concentrated in diseases of the ENT(Ear,Nose,and Throat),Ophthalmology,and diseases of the skin and subcutaneous tissue.When combined with drugs such as regulating Long lu,clearing heat toxin,and eliminating dampness-toxin,it is used to treat diseases such as Redness and visual obstruction due to corneal opacity,Oral ulcers,and Skin ulcers;For internal use,it is often combined with medicines that regulating Long lu,replenishing qi and blood,eliminating dampness-toxin,and nourishing the heart-mind,used in hypertension and palpitations.When paired with the medicines of clearing heat toxin,replenishing qi and blood,regulating Qiaowu,it is used to treat insomnia and epilepsy.Based on the analysis of pearl function,it is used in combination with airway and detoxifying drugs to treat airway diseases;Combination therapy with regulating Long lu and Qiao wu(brain)medicine for the treatment of Long lu disease;Combination treatment of gynecological diseases with regulating Long lu and Huo lu medicine and Bu xu medicine;Combination therapy with heat-clearing,detoxifying,and swelling-reducing medicines or astringents,for the treatment of persistent non-healing sores and ulcers;Used in combination with antipyretic drugs and yin tonifying drugs to treat ophthalmic diseases.Conclusion Zhuang medicine pearl has a wide range of therapeutic effects,and its efficacy can be enhanced by compatibility with different Zhuang medicines.Future research can combine modern compatibility methods of traditional Chinese medicine to optimize the compatibility scheme of pearls,study the specialized disease and prescription of Zhuang medicine pearls,combine Zhuang medicine with Western medicine to form prescriptions,and combine the pharmacological effects of pearls to form prescriptions.In depth exploration of the pharmacological substance basis and mechanism of action of pearl prescriptions can be conducted to develop new Zhuang medicine preparations for pearls.

Tumor vaccines face challenges such as low antigen delivery efficiency and significant side effects of carriers in stimulating specific anti-tumor immunity.Dendritic cell-derived exosomes(Dex),as endogenous nanovesicles,provide a new strategy for the development of novel vaccine carriers due to their excellent biocompatibility,targeted delivery capability and the ability to load intrinsic immune-active molecules.Dex can efficiently deliver tumor antigens,directly activate T,B and NK cells or indirectly promote antigen cross-presentation,and reshape the immune-suppressive microenvironment,thereby triggering a potent anti-tumor immune response.Studies have shown that Dex-based vaccines exhibit significant effects in inhibiting tumor growth and prolonging survival in models such as hepatocellular carcinoma and melanoma.This review summarizes the biological properties of Dex,its advantages as a vaccine carrier and the research progress in different tumor immunotherapies,aiming to provide references and ideas for further research on Dex in the field of vaccine carriers and to promote breakthroughs in its clinical application.

A microfluidic extracorporeal membrane oxygenator is an advanced extracorporeal life support device designed using microfluidic technology,capable of providing oxygenation support to patients with severe respiratory failure and other pulmonary diseases via extracorporeal circulation.Compared to conventional extracorporeal membrane oxygenators,it features a more superior biomimetic design,demonstrating potentials for improved therapeutic outcomes and reduced complications.This review summarizes the research progress of microfluidic extracorporeal membrane oxygenators in terms of hemodynamics,membrane materials,biocompatibility,gas exchange efficiency,and structural design.It analyzes how factors such as blood channel design,material selection and surface modification techniques impact the performance of microfluidic extracorporeal membrane oxygenators,such as biomimetic flow paths minimizing shear stress and endothelial cell linings significantly reducing thrombosis.Finally,the limitations of microfluidic extracorporeal membrane oxygenators are discussed,along with prospects for future development.Innovations are still needed in enhancing biocompatibility,portability,manufacturability,and cost reduction for microfluidic extracorporeal membrane oxygenators.