Background Acute cadmium (Cd) exposure can cause damage to multiple tissues, with the kidney being the primary target organ. The development of Cd-induced acute kidney injury involves complex mechanisms, in which autophagy and oxidative stress play crucial roles. Objective To investigate the effect of 10-hydroxy-2-decenoic acid (10-HDA) on kidney injury in mice exposed to cadmium, and provide experimental basis for studying the pathogenesis and prevention of Cd poisoning. Methods Thirty-five male C57BL/6 mice were divided into 7 groups (each of 5 mice): control group (normal saline, intraperitoneal injection), CdCl₂ group (4 mg·kg⁻¹, intraperitoneal injection), intervention groups ( 4 mg·kg⁻¹ CdCl₂, intraperitoneal Injection + 50, 100, 150, or 200 mg·kg⁻¹ 10-HDA, oral gavage), and 10-HDA group (150 mg·kg⁻¹, oral gavage). All treatments were given for 14 d. Twenty-four hours after the last infection, physiological indicators [blood urea nitrogen (BUN), creatinine (CRE), malondialdehyde (MDA), and superoxide dismutase (SOD)], histopathological indicators, autophagy-related proteins (Atg7, Atg5, Beclin-1, and LC3), and mitochondrial autophagy-related proteins (PINK1 and Parkin) were detected to examine the effect of 10-HDA on kidney injury caused by CdCl₂. Results Compared with the control group, the body weight of mice in the CdCl₂ group was significantly reduced (P<0.01); compared with the CdCl₂ group, the body weight of mice after intervention with different concentrations of 10-HDA was significantly increased (P<0.01). CdCl₂ significantly increased BUN and CRE in the serum samples compared with the control group (P<0.01), which was significantly reduced to varying degrees after 100, 150, and 200 mg·kg⁻¹ 10-HDA intervention (P<0.01). MDA significantly increased and SOD significantly decreased in the renal cortex following CdCl₂ administration compared with the control group (P<0.01), which was resolved following 10-HDA administration at different concentrations (P<0.01). In histopathological studies, 10-HDA restored injured kidney tissues induced by CdCl₂. The expression levels of autophagy proteins Atg7 and LC3-II/I were significantly increased (P<0.05), and the expression level of Beclin-1 was significantly decreased (P<0.05) in the CdCl₂ group compared with the control group. The expression levels of Atg7 were reduced to varying degrees after treatment with designed concentrations of 10-HDA, the expression levels of LC3-II/I were also reduced in the 50, 150, and 200 mg·kg⁻¹ 10-HDA intervention groups, and the expression levels of Beclin-1 were increased in the 50, 100, and 150 mg·kg⁻¹ 10-HDA intervention groups (P<0.05). The expression levels of PINK1 and Parkin in the CdCl₂ group and the 50 mg·kg⁻¹ 10-HDA intervention group were lower than those in the control group (P<0.01). Compared with the CdCl₂ group, the expression levels of PINK1 increased to varying degrees after 100, 150, and 200 mg·kg⁻¹ 10-HDA intervention, and the expression levels of Parkin increased in all 10-HDA intervention groups (P<0.01). Conclusion The intervention using 10-HDA can lessen acute kidney injury caused by CdCl₂, reduce the expression of autophagy-related proteins, and increase the expression of mitochondrial autophagy-related proteins.

Objective This clinical study aimed to evaluate the accuracy of a fully digital technique for mea-suring sagittal condylar inclination(SCI),as well as vali-dating whether differences existed between the left and right SCI values of the same participant,to provide a ref-erence for clinical practice.Methods Ten participants with good occlusal relationship and normal temporomandibular joint were recruited.Three methods were used to mea-sure the SCI values of the participants,namely,A(mechanical facebow transferring and mechanical articulator-based measuring method with physical protrusive interocclusal registration),B(face scan-based virtual facebow and virtual ar-ticulator-based measuring method with digital protrusive interocclusal registration),and C(jaw motion tracking system-based measuring method).With the group subjected to methods A and C as the control,the SCI values obtained by the three methods were statistically analyzed.The left and right SCI values of the same participant were also compared.Re-sults The left and right SCI values measured by method A were 41.70°±7.09° and 42.80°±8.62°,those by method B were 35.09°±12.49° and 37.63°±12.10°,and those by method C were 39.43°±8.72° and 38.45°±6.91°.No significant dif-ference existed among the SCI values measured by the three methods(P>0.05).Meanwhile,no statistical difference existed between the SCI values on the left and right sides of the same participant(P>0.05).Conclusion The accuracy of the virtual facebow and digital protrusive occlusal registration based SCI measuring method was the same as that of mechanical facebow based and jaw motion tracking system-based methods.The SCI values on the left and right sides of the same participant were similar.Clinically,an appropriate SCI measurement and setting strategy can be selected based on the actual situations.

Objective This clinical study aimed to as-sess the trueness of three intraoral scanners for the recor-ding of the maximal intercuspal position(MIP)to provide a reference for clinical practice.Methods Ten participants with good occlusal relationship and healthy temporomandibular joint were recruited.For the control group,facebow transferring procedures were performed,and bite registrations at the MIP were used to transfer maxillary and mandibular casts to a mechanical articulator,which were then scanned with a laboratory scanner to obtain digital cast data.For the experimental groups,three intraoral scanners(Trios 3,Carestream 3600,and Aoralscan 3)were used to obtain digital casts of the participants at the MIP following the scanning workflows endorsed by the corresponding manufacturers.Sub-sequently,measurement points were marked on the control group's digital casts at the central incisors,canines,and first molars,and corresponding distances between these points on the maxillary and mandibular casts were measured to calcu-late the sum of measured distances(DA).Distances between measurement points in the incisor(DI),canine(DC),and first molar(DM)regions were also calculated.The control group's maxillary and mandibular digital casts with the added mea-surement points were aligned with the experimental group's casts,and DA,DI,DC,and DM values of the aligned control casts were determined.Statistical analysis was performed on DA,DI,DC,and DM obtained from both the control and ex-perimental groups to evaluate the trueness of the three intraoral scanners for the recording of MIP.Results In the con-trol group,DA,DI,DC,and DM values were(39.58±6.40),(13.64±3.58),(14.91±2.85),and(11.03±1.56)mm.The Trios 3 group had values of(38.99±6.60),(13.42±3.66),(14.55±2.87),and(11.03±1.69)mm.The Carestream 3600 group showed values of(38.57±6.36),(13.56±3.68),(14.45±2.85),and(10.55±1.41)mm,while the Aoralscan 3 group had val-ues of(38.16±5.69),(13.03±3.54),(14.23±2.59),and(10.90±1.54)mm.Analysis of variance revealed no statistically sig-nificant differences between the experimental and control groups for overall deviation DA(P=0.96),as well as local devi-ations DI(P=0.98),DC(P=0.96),and DM(P=0.89).Conclusion With standardized scanning protocols,the three intra-oral scanners demonstrated comparable trueness to traditional methods in recording MIP,fulfilling clinical requirements.

In recent years,the tumor microenvironment(TME)has garnered significant attention from scientists.It is a com-plex system composed of tumor cells,cancer-associated fibroblasts(CAFs),immune cells,blood vessels,extracellular matrix,sur-rounding supportive tissues and their metabolic environment.Two fundamental characteristics of this system are immune escape and metabolic changes(the shift from aerobic to anaerobic metabolism of glucose,leading to lactate production).Although lactate has tra-ditionally been considered a metabolic"waste"product in the TME,it is now widely recognized that the increase in lactate and the acidification of the tumor microenvironment play key roles in tumor development and progression,including immune escape,tissue in-vasion/tumor metastasis,angiogenesis and tumor drug resistance.Therefore,studying the regulatory mechanisms of lactate metabo-lism,immune suppression,angiogenesis,and tumor drug resistance in the TME can provide a theoretical basis and practical evidence for new therapeutic strategies targeting the TME.

Objective:To explore effect of Glioma-associated oncogene family zinc finger 1(GLI1)on hypoxia induced trans-formation of NR8383 to M1 phenotype and development of pulmonary hypertension(PH).Methods:Fifteen adult male Wistar rats were randomly divided into control group,hypoxia PH model group and hypoxic PH with GANT61 treatment group,with 5 rats in each group.PH related indexes of rats were detected by small animal ultrasound and right cardiac catheter experiment to determine effect of GLI1 specific inhibitor GANT61 on progression of PH.Pulmonary arterial thickness was measured by HE staining.α-SMA and M1 polarization markers TNF-α and IL-1β expressions were determined by immunohistochemistry.M1 polarization markers CD86 and TNF-α expressions were determined by immunofluorescence.GLI1 expression and NF-κB protein were detected by Western blot.mRNA expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 were detected by qRT-PCR.CHIP-PCR verified that GLI1 regulates NF-κB promoter activity.IL-12 content was detected by ELISA.Rat pulmonary artery smooth muscle cells proliferation was detected by CCK-8.Results:GLI1 inhibitor GANT61 could alleviate symptoms of PH in hypoxic rats(P<0.05).Compared with hypoxic group,inhibition of GLI1 reduced expressions of TNF-α and IL-1β in rat lung tissue(P<0.05).In cell experiments,hypoxia induced M1 polarization of NR8383 by up-regulating GLI1 to activate NF-κB pathway,GLI1 overexpression increased expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 in M1 macrophages(P<0.05).NR8383 culture supernatants could stimulate pulmonary artery smooth muscle cell proliferation(P<0.05)and contribute to development of PH.Conclusion:Hypoxia activates NF-κB pathway by up-regulating GLI1 to induce M1 polarization of macrophages contributes to development of PH.

Objective To explore method of establishing and evaluating an asthma rat model with phlegm and blood stasis syndrome.Methods 60 SD male rats were randomly divided into 5 groups,a normal group,asthma group,combination of disease and syndrome(combination)group,DM group,and KCLW group,with 12 rats in each group.Asthma models were established using ovalbumin(OVA).A syndrome model of phlegm and blood stasis was established using a high-fat diet combined with the ice water bath method.We evaluated the asthma model through animal behavior observation,pathological section observation,inflammation index detection,and airway reactivity measurements.The phlegm and blood stasis syndrome model was evaluated via measurements of rat body mass,blood glucose,blood lipids,coagulation function,and hemorheological indexes and by observing symptoms and syndrome determination by Kechuan Liuwei mixture.Results(1)After OVA induction,the rats in the asthma model group and combination group showed symptoms such as shortness of breath,open mouth breathing,abdominal movement,restlessness,and irritability.HE staining showed the disordered arrangement of the bronchial mucosa in lung tissue,local detachment,thickening of the basement membrane and the bronchial tube wall,narrowing of the lumen,extensive infiltration of inflammatory cells,and congestion of capillaries.Compared with the normal group,the asthma model group and combination group(P＜0.05)had increased serum IL-4,IL-6,and TGF-β1.Penh values were increased after stimulation with various concentrations of Mch(P＜0.05).(2)Rats in the combination group showed symptoms such as chills,curling up with minimal movement,purple and dark claws,purple and black bruises on the tail,loose stools,and unclean perianal area.Compared with the rats in the asthma model group,rats in the combination group had increased body mass(P＜0.05)and blood glucose,triglyceride,and total cholesterol levels(P＜0.05),a shortened thrombin time(P＜0.05),increased fibrinogen content(P＜0.05),and significantly increased whole-blood viscosity at low,medium,and high shear rates(P＜0.05).The indexes were significantly improved after Kechuan Liuwei mixture administration.Conclusions The asthma rat model with phlegm and blood stasis syndrome can be established through OVA induction and high-fat diet combined with ice water bath.The model can be evaluated through behavioral observation,index measurements,and syndrome determination via formulas.

Objective:To discuss the effect of adipose-derived stem cell-derived exosomes(ADSC-Exos)on the migration ability of the macrophages RAW264.7,and to clarify its role in promoting function of the macrophages.Methods:The adipose tissue adjacent to epididymis of the SD rats was isolated to perform primary culture of the adipose-derived stem cells(ADSCs).The adipogenic and osteogenic differentiation induction was conducted,and the multidirectional differentiation potential of the ADSCs was detected by oil Red O and Alizarin red staining.Western blotting and immunofluorescence methods were used to detect the positive expressions of the ADSCs markers CD29 and CD44;the ADSC-Exos were extracted by Exos isolation kit,and the morphology,size,and distribution of particle size of the ADSC-Exos were examined by transmission electron microscope and nanoparticle tracking analyzer;the expression levels of exosome-specific markers CD9 and TSG101 proteins in the ADSC-Exos were detected by Western blotting method;the uptake of ADSC-Exos by the macrophages was observed by tracing method.The macrophages RAW264.7 were divided into control group,10 mg·L-1 ADSC-Exos group,20 mg·L-1 ADSC-Exos group,and 40 mg·L-1 ADSC-Exos group.The activities of the macrophages in various groups were detected by 5-ethynyl-2'-deoxyuridine(EdU)staining;the number of migration macrophages in various groups was detected by Transwell chamber assay;the adhesion of macrophages in various groups was observed by fluorescence microscope.Results:After 24 h of primary culture,the ADSCs adhered to the wall and exhibited scattered,elongated shapes;after 7 d of culture,the adherent cells showed a comb-like,vortex-like orderly arrangement,resembling fibroblasts;after 10 passages,the irregular morphology of the ADSCs and decreased proliferation rate were found.The isolated ADSCs showed potential for the osteogenic and adipogenic differentiation,and the expressions of CD29 and CD44 proteins were positive.The transmission electron microscope observation resuls showed that the ADSC-Exos appeared disc-shaped,and the main peak of particle size distribution was around 132 nm.The CD9 and TSG101 proteins were positively expressed in the ADSC-Exos,indicating successful extraction.The fluorescence microscope results showed red fluorescence signals around the nuclei of the RAW264.7 cells,indicating the uptake of ADSC-Exos by the macrophages.Compared with control group,the rates of EdU positive cells in 10,20,and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05);compared with 10 mg·L-1 ADSC-Exos group,the rate of EdU positive cells in 20 mg·L-1 ADSC-Exos group was significantly increased(P<0.05).Compared with control group,the numbers of migration cells in 10,20,and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05);compared with 10 mg·L-1 ADSC-Exos group,the numbers of migration cells in 20 and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05).Compared with control group,the numbers of the adherent macrophages in 10,20,and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05);compared with 10 mg·L-1 ADSC-Exos group,the number of adherent macrophages in 20 mg·L-1 ADSC-Exos group was significantly increased(P<0.05).Conclusion:The ADSC-Exos can be internalized by the macrophages and they can enhance the migration ability of the macrophages by affecting the cell adhesion.

Objective:To investigate the factors influencing the occurrence of esophageal stenosis after endoscopic radiofrequency ablation (RFA) for total or near total circumferential early esophageal cancer and precancerous lesions.Methods:Between November 2018 and April 2022, 37 patients who underwent RFA for early esophageal squamous cell carcinoma or intraepithelial neoplasia at Zhongda Hospital, Southeast University were included in a case-control study, and were divided into two groups based on the occurrence of postoperative esophageal stricture: the group with postoperative esophageal stenosis (case group, n=15) and the group without postoperative esophageal stenosis (control group, n=22). The differences in general information, endoscopic findings, and surgical procedures between the two groups were analyzed. Results:There was no significant difference in gender ( P=0.708), age ( t=1.106, P=0.413), smoking or drinking ( P=0.329), preoperative pathology ( P=0.194), circumferential situation ( P=1.000), Paris type ( P=0.379), lesion length ( t=-0.825, P=0.927), ablation length ( t=-0.134, P=0.723), ablation times ( P=0.306), or interval between each ablation ( P=0.500) between the two groups; however, there was significant difference in invasion depth between the two groups ( P=0.021). Conclusion:For total or near total circumferential early esophageal cancer and precancerous lesions, the depth of lesion infiltration may affect the occurrence of esophageal stenosis after RFA. The likelihood of esophageal stenosis may rise with increased infiltration depth, suggesting a need for further research to validate these findings.

[Objective]To establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of 5-hydroxytryptamine(5-HT)and 5-hydroxyindole acetic acid(5-HIAA)in mouse serum and hippocampus,applied to the evaluation of the antidepressant efficacy of traditional Chinese medicine.[Methods]The serum and hippocampus were taken and the concentrations of 5-HT and 5-HIAA were determined by LC-MS/MS after pretreatment of protein precipitation.Chromatographic separation was performed on Hypersil ODS(250 mm×4.6 mm,5 μm)at column temperature of 40℃.The mobile phase was 0.1%formic acid-water solution with 2 mmol·L-1 ammonium acetate and acetonitrile whereas flow rate was set at 1 mL·min-1.The mass spectrometry detection was performed using multiple reaction monitoring(MRM).One hundred and ninety-eight mice were randomly divided into normal control group,model group,fluoxetine hydrochloride group and 30 groups of Paeoniae Radix Alba with 6 rats in each group.Tail suspension test and forced swimming test were carried out.[Results]5-HT and 5-HIAA had good linear relationship within the concentration range of 0.1～1 000 ng·mL-1 and 1～500 ng·mL-1,respectively(r>0.999).Precision and recovery of this method were in line with the requirements of biological sample analysis.The degree of change in 5-HIAA/5-HT values in the Paeoniae Radix Alba group relative to the model group was correlated with the degree of change in indicators of the behavioral experiment,and the degree of change was significantly higher than that of the behavioral experiment,with a much smaller within-group relative standard deviation(RSD).[Conclusion]This LC-MS/MS method is simple and fast for operation,with accurate results,high sensitivity,good reproducibility and strong specificity which indicated that was suitable for the simultaneous determination of 5-HT and 5-HIAA in serum and hippocampus.It could be used for research and efficacy evaluation of neuroprotective drugs like Paeoniae Radix Alba.

In order to make the shared traditional Chinese medicine （TCM） pharmacy develop more efficiently and normatively at the grass-roots level， using the “shared TCM pharmacy” as the retrieval word， this paper uses the literature research method to retrieve the reports， documents and policies from CNKI， the websites of people’s governments at all levels， the official websites of the State Administration of Traditional Chinese Medicine， people.com， China News Network， Xinhua News and other platforms before May 20， 2022， sort out the development mode and history of two “Internet plus” TCM pharmacies， namely “shared TCM pharmacies” and “smart TCM pharmacies”， and compare them with each other. Combined with the actual work of community hospitals and community service centers （stations）， the necessity and advantages （such as reducing the costs of the intermediate links of drug circulation and standardizing the grass-roots drug use process） of the development of “shared TCM pharmacy” are obtained from the perspective of primary medical care. Combined with the current situation of the promotion and application of shared TCM pharmacy in county medical communities， it is concluded that the shared TCM pharmacy should be further constructed from four aspects： improving the work process of drug centralized procurement under the background of normalization， improving the compatibility and synchronization of the whole process dispensing information system module， unifying pharmaceutical services and personnel training， defining the authority of data query and clarifying the boundaries of patient privacy to further build a shared TCM pharmacy. Finally， it integrates information technology， summarizes the definition of shared TCM pharmacy and its future construction direction， and provides reference for the next development of shared TCM pharmacy at the grass-roots level.