Diabetic kidney disease(DKD)is one of the most important complications of diabetes.In recent years,domestic and foreign studies have found that mammalian target protein of rapamycin(mTOR)related signaling pathway is a classic pathway involved in the regulation of autophagy,which can achieve the therapeutic effect of DKD by targeting the autophagy pathway,and plays a crucial role in the prevention and treatment of DKD.In this paper,we reviewed the mechanism of mTOR-related signaling pathway targeted autophagy in the prevention and treatment of DKD,in order to provide a new reference and basis for clinical prevention and treatment of DKD.

The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

Orodispersible films (oral dispersible films), a novel form of oral solid dosage forms, are widely used for patients with dysphagia and those with uncontrollable autonomic behavior. In this study, suvorexant orodispersible film was prepared by hot melt extrusion technology, and the disintegration time, mechanical properties, in vitro dissolution and pharmacokinetics were evaluated, compared with other orodispersible films and commercially available tablets Belsomra. All experiments were approved by the Committee on the Management and Use of Laboratory Animals of Academy of Military Medical Sciences (IACUC-DWZX-2024-504). The results showed that the dissolution rate of suvorexant orodispersible film was faster and the mechanical strength was better than that of other commercially available orodispersible film, which could meet the needs of storage and transportation. Differential scanning calorimetry and X-ray diffraction results showed that suvorexant was dispersed within the orodispersible film in an amorphous state. The in vitro dissolution of the film was observed to be four times faster than that of the commercial tablets, achieving complete dissolution within five minutes. Pharmacokinetic evaluations in Beagle dogs revealed that the self-formulated orodispersible film exhibited no significant differences in the area under the blood concentration-time curve when compared with Belsomra. However, the film showed a faster onset of action, with a peak time that was twice as rapid, and a maximum blood concentration that was twice as high as that of Belsomra. Leveraging hot melt extrusion technology, the suvorexant orodispersible film offers a straightforward, continuous production process with consistent quality. It serves as an excellent platform for the development of solvent-free film preparations tailored for patients with special needs.

The rheological properties of drug and carrier materials have a wide range of guiding significance for the formulation and process development of solid dispersions. In this study, the rheological properties of materials with different drug carrier ratios were systematically studied with suvorexant as the model drug and copovidone as the carrier material, which provided a sufficient basis for determining the formulation and process of solid dispersions. The optimal suvorexant-copovidone ratio obtained by oscillating temperature scanning was 1∶4. If the ratio is greater than 1∶ 4, the glass transformation temperature of the material will increase significantly, and the solubilization effect of the solid dispersion will show a downward trend. The results of oscillation temperature scanning and oscillation temperature sweep can show that when the extrusion temperature is greater than 150 ℃, the viscosity of the material is less than 10 000 Pa·s, and the melt can be extruded smoothly, and the best extrusion temperature of 160-180 ℃ can be obtained by combining the dissolution results. Finally, the dissolution of suvorexant tablets guided by rheological property studies in multiple media is similar to that of the commercially available tablets Belsomra. Therefore, rheological studies can screen and optimize the formulation and process of suvorexant solid dispersions at the mechanism level, which is of great significance to improve the success rate of R&D and shorten the R&D cycle of solid dispersions prepared by hot melt extrusion.

Objective To evaluate the rabbit modle of frozen shoulder induced by persistent strain injuries and ice com-pression.Methods Twelve clean,healthy male New Zealand rabbits with a mass of(2 500±500)g were selected and randomly divided into a blank group and a control group with 6 rabbits in each group.In the control group,the rabbits were modeled with persistent strain injuries and ice compression,the general conditions of the rabbits and the active and passive activities of the shoulder joint were observed and their body weights were recorded.MRI was performed on the affected shoulder joints at 6 d and 29 d after modelling to observe the fluid and soft tissue;HE staining was used to observe the morphology of the rabbit bi-ceps longus tendon and the synovial membrane of the joint capsule;Masson staining was used to observe the fibrous deposits of the rabbit biceps longus tendon and the synovial membrane of the joint capsule,and the fibrous deposits were analysed semi-quantitatively by Image J software.Results Six days after the end of modeling,the active movement of the shoulder joints in the control group was limited,the passive movement was not significantly limited,and they walked with a limp;29 days after the end of the modeling,the active and passive movements of the shoulder joints in the model group were severely limited.Com-pared with the blank group(2.50±0.14)kg,the body weight of the model group(2.20±0.17)kg was significantly reduced(P＜0.01).MRI showed that 6 days after modelling,the muscles around the shoulder joint were not smooth in shape,the joint cap-sule structure was narrowed and a large amount of fluid was seen in the joint cavity;29 days after modelling,the muscles around the shoulder joint were rough in shape,structure of the joint capsule was unclear and the fluid in the joint cavity was reduced compared with 6 days after modelling.Pathological staining showed that the long-headed biceps tendon fibres in the control group were disorganised,curled or even broken,and the synovial tissue of the joint capsule was heavily vascularised,with col-lagen fibre deposits and severe inflammatory cell infiltration.The fiber deposition of the long head of biceps brachii in the mod-el group[(23.58±3.41)％,(27.56±3.70)％]and synovial tissue[(41.78±5.59)％,(62.19±7.54)％]were significantly higher than those in the blank group[(1.79±1.03)％,(1.29±0.63)％]at 7 and 30 days after modeling and synovial tissue fiber de-position[(8.15±3.61)％,(11.29±7.10)％],as shown by the semi-quantitative analysis of Masson staining results by Image J software.And the longer the time,the more severe the fibrosis(P＜0.01).Conclusion The behavioral,imaging and pathological findings showed that the rabbit frozen shoulder model with persistent strain injuries and ice compression is consistent with the clinical manifestations and pathogenesis of periarthritis,making it an ideal method for periarthritis research.

Objective To compare clinical efficacy of robot-assisted(RA)and remote sensing navigation alignment(RSNA)system-assisted total knee arthroplasty(TKA).Methods From March 2023 to June 2023,60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis(KOA)were admitted and divided into RSNA group and RA group according to different treatment methods,with 30 patients in each group.There were 5 males and 25 females in RSNA group,aged from 56 to 81 years old with an average of(66.33±7.16)years old;body mass index(BM1)ranged from 19.87 to 38.54 kg·m-2 with an average of(28.40±6.18)kg·m-2;the courses of disease ranged from 5 to 36 months with an average of(18.20±8.98)months;RSNA system was used to assist the positioning of osteotomy.There were 7 males and 23 females in RA group,aged from 55 to 82 years old with an average of(67.83±8.61)years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an aver-age of(28.01±4.89)kg·m-2;the courses of disease ranged from 3 to 33 months with an average of(17.93±9.20)months;RA was performed.Operation time,incision length,latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups.Hip-knee ankle angle(HKAA),HKAA deviation,lateral distal femoral angle(LDFA),medial proximal tibial angle(MPTA)and posterior tibial slope(PTS)were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index(WOMAC)and Knee Society score(KSS)were used to evaluate functional recovery before operation,3 and 6 months after operation.Results The operation was performed successfully in both groups,and there were no serious complications such as vascular and nerve injury during operation.The wound healed well at stage Ⅰafter operation,and the follow-up time was 6 months.The operation time,latent blood loss at 2 weeks after operation and inci-sion length in RSNA group were(94.35±5.75)min,(130.54±17.53)mland(14.73±2.14)cm,respectively;while(102.57±6.88)min,(146.33±19.47)ml and(16.78±2.32)cm in RA group,respectively.RSNA group was better than RA group(P＜0.05).No deep vein thrombosis occurred in both groups at 2 weeks after operation,5 patients occurred intermuscular vein throm-bosisin in RSNA group and 8 patients in RA group,the difference was not statistically significant(P＞0.05).In RSNA group,HKAA,LDFA and MPTA were(173.00±5.54)°,(86.96±3.45)°,(82.79±3.35)° before operation,and(178.34±1.85)°,(89.92±0.42)°,(89.84±0.73)° at 1 week after operation,respectively.In RA group,HKAA,LDFA and MPTA were(173.31±6.48)°,(87.15±3.40)° and(82.99±3.05)° before operation,and(178.52±1.79)°,(90.03±0.39)° and(90.15±0.47)° at 1 week after operation,respectively.HKAA,LDFA and MPTA were significantly improved in both groups at 1 week after oper-ation(P＜0.05).There were no significant difference in HKAA,LDFA,MPTA and PTS between two groups before operation and 1 week after operation(P＞0.05).There was no significant difference in deviation distribution of HKAA at 1 week after op-eration(x2=2.61 1,P=0.456).There were no significant difference in WOMAC and KSS between two groups before operation,3 and 6 months after operation(P＞0.05),and postoperative WOMAC and KSS at 3 and 6 months between two groups were im-proved compared with those before operation(P＜0.05).Conclusion Both RA and RSNA system assisted TKA could obtain ac-curate osteotomy,RA has higher surgical accuracy,RSNA system assisted operation has less trauma,and operation is simpler.

Objective To explore clinical accuracy of remote sensing navigation alignment(RSNA)system in total knee arthroplasty(TKA)and its influence on postoperative clinical efficacy.Methods From May 2021 to May 2022,60 knee os-teoarthritis(KOA)patients with Kellgren-Lawrence(K-L)grade Ⅲ to Ⅳ treated by unilateral primary TKA were selected and divided into RSNA group and traditional operation group according to treatment methods,and 30 patients in each group.There were 6 males and 24 females in RSNA group,aged from 55 to 86 years old with an average of(68.06±8.23)years old;body mass index(BMI)ranged from 22.15 to 34.58 kg·m-2 with an average of(28.20±3.01)kg·m-2;the courses of disease ranged from 2 to 60 months with an average of(18.80±14.80)months;13 patients with grade Ⅲ and 17 patients with grade Ⅳaccording to K-L grading.In traditional operation group,there were 8 males and 22 females,aged from 57 to 85 years old with an average of(67.26±6.32)years old;BMI ranged from 23.94 to 34.55 kg·m-2 with an average of(27.49±2.32)kg·m-2;the courses of disease ranged from 3 to 60 months with an average of(21.30±16.44)months;14 patients with grade Ⅲ and 16 pa-tients with grade Ⅳ according to K-L grading.Western Ontario and McMaster Universities(WOMAC)osteoarthritis index and Knee Society score(KSS)were used to evaluate functional recovery of patients.Hip-knee-ankle angle(HKAA),distal femoral valgus angle(FVA)and distal fermoral flexion angle(DFFA)were measured before operation.HKAA and HKAA deviation angle were measured at 1 week after operation,and defective rate of lower limb force line,femur prosthesis valgus angle(FP-VA)and femoral prosthesis flexion angle(FPFA),respectively,were calculated.Results There were no serious complications such as vascular and nerve injury during operation,and wound healed at stage Ⅰ.Both groups were followed up for 6 months.There were no significant difference in WOMAC index,KSS,HKAA,FVA and DFFA between two groups before operation(P＞0.05).The force line defect rate,HKAA,HKAA deviation angle,FPVA deviation angle and FPFA of RSNA group were 6.7％,(178.74±1.56)°,(1.25±1.56)°,(1.84±0.16)° and(4.85±2.46)°,respectively;while in traditional operation group were 20％,(176.73±3.46)°,(3.27±3.46)°,(2.44±0.26)°,(6.60±1.86)°;the difference between two groups were statistically sig-nificant(P＜0.05).There were no significant difference in WOMAC index and KSS between two groups at 3 and 6 months after operation(P＞0.05).Conclusion RSNA system could reduce defective rate of lower limb force line,FPVA deviation angle and FPFA after TKA,which is more accurate and easy to operate than traditional intramedullary localization surgery while ensuring postoperative efficacy.

Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is one of the most common complications after endoscopic retrograde cholangiopancreatography(ERCP).Numerous PEP prediction models have been established based on different statistical methods at home and abroad.The PEP prediction model,as a tool for evaluating and screening high-risk populations,can provide a basis for medical staff to find high-risk PEP patients early and take effective preventive measures.In recent years,new PEP prediction models have appeared one after another,but there is still a lack of recognized reliable prediction models in clinic.This article reviews the research status of PEP risk prediction models,aim to provide a direction for establishing a more reliable,accurate,and practical PEP risk prediction model in the later period.

This study was aimed at exploring the epidemiological characteristics of plague,and the evolutionary relation-ships among the isolated plague strains in the Yunnan border area,to provide clues for further studying epidemic causes and ep-idemiological patterns.Plague epidemic data in the border area during the second epidemic period(1982-2007)were collected and analyzed with descriptive epidemiological methods.Whole genome sequences of 262 strains of Yersinia pestis in the border area were obtained for phylogenetic analysis.Plague outbreaks occurred in 17 counties(cities)among 25 border counties(cit-ies);a total of 552 epidemic foci and 123 human cases were identified.The 1.ORI2,1.ORI3,1.IN3,2.ANT and 2.MED geno-types were identified among Yersinia pestis isolated from the Yunnan border area,among which the 1.ORI2 population was dominant.A total of 258 strains of Yersinia pestis from the 1.OR12 population belonged to four subclusters.The Myanmar and Vietnam clade was embedded within the Yunnan clade in the overall phylogeny.The above results indicated that during the sec-ond period of the epidemic,the intensity of plague epidemics in Yunnan's border areas was high,showing a trend of devel-opment from west to south and east.Our findings indicated a risk of cross-border transmission of plague between Yunnan and neighboring countries;therefore,the surveillance,pre-vention,and control of plague in border areas should be strengthened.

AIM To study the chemical constituents from Codonopsis pilosula(Franch.)Nannf in Shanxi and their anti-inflammatory activities.METHODS The 70％ ethanol extract from C.pilosula in Shanxi was isolated and purified by silica gel,ODS and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their in vitro anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as ethylsyringin(1),7-O-ethyltangshenoside Ⅱ(2),triandrin(3),trans-isoconiferin(4),methylsyringin(5),9-acetoxy syringin(6),cordifolioidyne B(7),codonopiloenynenoside A(8),codonopilodiynoside F(9),pratialin B(10),lobetyolinin(11),lariciresinol-4-O-β-D-glucoside(12),dihydrodehydrodiconiferyl alcohol 4′-O-β-D-glucoside(13),atractylenolid Ⅲ(14),baimantuoluoamide B(15),benzyl primeveroside(16).Compounds 1-2,5,7-11 and 13-15 had certain anti-inflammatory activities,among which compounds 11,14-15 had higher activities,whose IC50 values were(18.23±4.18),(17.73±3.12),(14.89±2.47)μmol/L,respectively.CONCLUSION Compounds 3,6,13,16 are first isolated from Campanulaceae,2,5,15 are first found from this plant.Compounds 11,14 and 15 have good anti-inflammatory activities.