Objective:This study aimed to evaluate whether intra-articular delivery of conditioned medium(CM)derived from stem cells of human exfoliated deciduous teeth(SHED)could influence the progression of condylar cartilage degeneration in a rat model of temporomandibular joint osteoarthritis(TMJ OA).Methods:Sixty 8-week-old male SD rats were randomly divided into control group(CON group),intraarticular injection of MIA induced TMJ OA model group(MIA group),and injection of SHED condi-tioned medium 1 week after MIA modeling for treatment group(SHED-CM group),with 20 animals in each group.Histological sec-tions,HE,Safranine O-solid green staining,Col Ⅱ immunohistochemical staining,and TUNEL staining were performed 2 and 4 weeks after the start of treatment.Western blotting and RT-qPCR were used to detect the key molecules of apoptosis,cleaved-CASP3,BAX and BCL2,pro-inflammatory related factors IL-1β,IL-6,TNFα,MMP3,ADAMTS5,and the MAPK pathway-related molecules p-ERK,ERK,p-P38 and P38.Results:Compared with the CON group and SHED-CM group,the condyle chondrocytes in the MIA group had disordered arrange-ment,interrupted layers,significantly thickened fibrous layers(P＜0.001),and significantly increased Mankin's OA histological score(P＜0.001).In the MIA group,both the Safranin O-positive area ratio and the proportion of ColⅡ-positive regions were markedly reduced compared with the CON and SHED-CM groups(P＜0.001).Conversely,the proportion of TUNEL-positive cells was substantially higher than in the other two groups(both P＜0.001).Western blot analysis further demonstrated that apoptotic markers(cleaved-CASP3,BAX/BCL2)and MAPK pathway-related proteins(p-ERK,ERK,p-P38,P38)were expressed at significantly elevated levels in the MIA group relative to CON and SHED-CM groups(BAX/BCL2:P＜0.05;cleaved-CASP3:P＜0.01;p-P38/P38:P＜0.001;p-ERK/ERK:P＜0.01).Similarly,qRT-PCR revealed upregulated expression of inflammatory mediators,including IL-1 β(P＜0.001),IL-6(P＜0.01),TNFα(P＜0.01),MMP3(P＜0.001),and ADAMTS5(P＜0.05),in the MIA group compared with the CON and SHED-CM groups.Conclusion:SHED-CM treatment can ef-fectively reverse MIA-induced condylar cartilage degeneration of TMJ OA in rats.

Objective:To evaluate the efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy.Methods:In this multicenter, non-inferiority, randomized controlled trial, 300 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 18-60 yr, with body mass index of 18-28 kg/m 2, who underwent daytime laparoscopic cholecystectomy under general anesthesia with tracheal intubation at Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou First People′s Hospital Affiliated to Westlake University School of Medicine, Ningbo No. 2 Hospital, and the Second Affiliated Hospital of Nanchang University from August 2021 to August 2023, were selected and divided into 2 groups ( n=150 each) using a random number table method: remimazolam group (R group) and propofol group (P group). Anesthesia was induced as follows: Sufentanil was intravenously injected at a rate of 0.5 μg/kg, remimazolam was intravenously injected at a rate of 0.3 mg/kg in group R, propofol was intravenously injected at a rate of 2.0-2.5 mg/kg in group P, and cisatracurium besilate was intravenously injected at a rate of 0.2 mg/kg after loss of consciousness in two groups. The patients were mechanically ventilated after tracheal intubation. Anesthesia was maintained as follows: Remimazolam was intravenously injected at a rate of 0.5-1.0 mg·kg -1·h -1 in group R, propofol was intravenously injected at a rate of 4-10 mg·kg -1·h -1 in group P, and remifentanil was intravenously infused at a rate of 0.25-2.00 μg·kg -1·min -1, maintaining intraoperative bispectral index value of 40-60. The success rate of sedation was recorded, and non-inferiority tests were conducted. The time to loss of consciousness, emergence time, extubation time, recovery time of orientation, time of stay in post-anesthesia care unit and occurrence of delayed emergence were recorded. Liver function and renal function were measured before operation and within 24 h after operation. The occurrence of abnormal alanine transaminase, abnormal aspartate transaminase, abnormal creatinine and abnormal urea was recorded. The occurrence of adverse reactions during and after operation was recorded. Results:The success rates of sedation were 98.6% and 99.3% in group R and group P, respectively, there was no statistically significant difference in the success rate of sedation between the two groups ( P>0.05), and the difference in the success rates of sedation between the two groups was -0.007 (95% confidence interval-0.0301-0.0161), which met the pre-set non-inferiority criteria(95% confidence interval >-0.055). Compared with group P, the time to loss of consciousness and recovery time of orientation were significantly prolonged, and the incidence of delayed emergence was increased ( P<0.05), and no statistically significant changes were found in the emergence time, extubation time, time of stay in post-anesthesia care unit and severity of postoperative nausea and vomiting in group R ( P>0.05). There was no statistically significant difference in the abnormal rates of alanine transaminase, aspartate transaminase, creatinine and urea before and after operation between the two groups ( P>0.05). Conclusions:The efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy is not inferior to that of propofol-based anesthesia.

Objective:This study aimed to evaluate whether intra-articular delivery of conditioned medium(CM)derived from stem cells of human exfoliated deciduous teeth(SHED)could influence the progression of condylar cartilage degeneration in a rat model of temporomandibular joint osteoarthritis(TMJ OA).Methods:Sixty 8-week-old male SD rats were randomly divided into control group(CON group),intraarticular injection of MIA induced TMJ OA model group(MIA group),and injection of SHED condi-tioned medium 1 week after MIA modeling for treatment group(SHED-CM group),with 20 animals in each group.Histological sec-tions,HE,Safranine O-solid green staining,Col Ⅱ immunohistochemical staining,and TUNEL staining were performed 2 and 4 weeks after the start of treatment.Western blotting and RT-qPCR were used to detect the key molecules of apoptosis,cleaved-CASP3,BAX and BCL2,pro-inflammatory related factors IL-1β,IL-6,TNFα,MMP3,ADAMTS5,and the MAPK pathway-related molecules p-ERK,ERK,p-P38 and P38.Results:Compared with the CON group and SHED-CM group,the condyle chondrocytes in the MIA group had disordered arrange-ment,interrupted layers,significantly thickened fibrous layers(P＜0.001),and significantly increased Mankin's OA histological score(P＜0.001).In the MIA group,both the Safranin O-positive area ratio and the proportion of ColⅡ-positive regions were markedly reduced compared with the CON and SHED-CM groups(P＜0.001).Conversely,the proportion of TUNEL-positive cells was substantially higher than in the other two groups(both P＜0.001).Western blot analysis further demonstrated that apoptotic markers(cleaved-CASP3,BAX/BCL2)and MAPK pathway-related proteins(p-ERK,ERK,p-P38,P38)were expressed at significantly elevated levels in the MIA group relative to CON and SHED-CM groups(BAX/BCL2:P＜0.05;cleaved-CASP3:P＜0.01;p-P38/P38:P＜0.001;p-ERK/ERK:P＜0.01).Similarly,qRT-PCR revealed upregulated expression of inflammatory mediators,including IL-1 β(P＜0.001),IL-6(P＜0.01),TNFα(P＜0.01),MMP3(P＜0.001),and ADAMTS5(P＜0.05),in the MIA group compared with the CON and SHED-CM groups.Conclusion:SHED-CM treatment can ef-fectively reverse MIA-induced condylar cartilage degeneration of TMJ OA in rats.

Objective:To evaluate the efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy.Methods:In this multicenter, non-inferiority, randomized controlled trial, 300 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 18-60 yr, with body mass index of 18-28 kg/m 2, who underwent daytime laparoscopic cholecystectomy under general anesthesia with tracheal intubation at Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou First People′s Hospital Affiliated to Westlake University School of Medicine, Ningbo No. 2 Hospital, and the Second Affiliated Hospital of Nanchang University from August 2021 to August 2023, were selected and divided into 2 groups ( n=150 each) using a random number table method: remimazolam group (R group) and propofol group (P group). Anesthesia was induced as follows: Sufentanil was intravenously injected at a rate of 0.5 μg/kg, remimazolam was intravenously injected at a rate of 0.3 mg/kg in group R, propofol was intravenously injected at a rate of 2.0-2.5 mg/kg in group P, and cisatracurium besilate was intravenously injected at a rate of 0.2 mg/kg after loss of consciousness in two groups. The patients were mechanically ventilated after tracheal intubation. Anesthesia was maintained as follows: Remimazolam was intravenously injected at a rate of 0.5-1.0 mg·kg -1·h -1 in group R, propofol was intravenously injected at a rate of 4-10 mg·kg -1·h -1 in group P, and remifentanil was intravenously infused at a rate of 0.25-2.00 μg·kg -1·min -1, maintaining intraoperative bispectral index value of 40-60. The success rate of sedation was recorded, and non-inferiority tests were conducted. The time to loss of consciousness, emergence time, extubation time, recovery time of orientation, time of stay in post-anesthesia care unit and occurrence of delayed emergence were recorded. Liver function and renal function were measured before operation and within 24 h after operation. The occurrence of abnormal alanine transaminase, abnormal aspartate transaminase, abnormal creatinine and abnormal urea was recorded. The occurrence of adverse reactions during and after operation was recorded. Results:The success rates of sedation were 98.6% and 99.3% in group R and group P, respectively, there was no statistically significant difference in the success rate of sedation between the two groups ( P>0.05), and the difference in the success rates of sedation between the two groups was -0.007 (95% confidence interval-0.0301-0.0161), which met the pre-set non-inferiority criteria(95% confidence interval >-0.055). Compared with group P, the time to loss of consciousness and recovery time of orientation were significantly prolonged, and the incidence of delayed emergence was increased ( P<0.05), and no statistically significant changes were found in the emergence time, extubation time, time of stay in post-anesthesia care unit and severity of postoperative nausea and vomiting in group R ( P>0.05). There was no statistically significant difference in the abnormal rates of alanine transaminase, aspartate transaminase, creatinine and urea before and after operation between the two groups ( P>0.05). Conclusions:The efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy is not inferior to that of propofol-based anesthesia.

[This corrects the article DOI: 10.1016/j.apsb.2022.07.023.].

Objective:To investigate the effects of intra-articular injection of exosomes derived from dental pulp stem cells from hu-man exfoliated deciduous teeth(SHED-EXO)on subchondral bone homeostasis in rat temporomandibular joint osteoarthritis(TMJ OA)process.Methods:36 male SD rats were randomly divided into 3 groups(n=12):control(CON),sodium iodoacetate(MIA)-induced TMJ OA(MIA),and SHED-EXO injection into TMJ OA(SHED-EXO)groups.At 2 and 6 weeks post-treatment,Micro-CT,Double labeling,TRAP staining,and immunohistochemical staining were employed to detect osteoclasts and osteoblasts in the subchondral bone.Additionally,the mRNA expression levels of ADAMTs5,IL-1β,OCN and OPG/RANKL were analyzed by qRT-PCR.Results:The MIA group exhibited significant bone loss and an enlarged bone marrow cavity.In comparison with the CON group,BV/TV and Tb.Th were lower(P＜0.001),while BS/BV,Tb.Sp,and Tb.N were higher(P＜0.01).Additionally,the bone formation rate within 5 days was low-er than that of the control group(P＜0.001).When compared to the MIA group,the SHED-EXO group showed a significant increase in bone morphology and bone mass.BV/TV and Tb.Th were increased(P＜0.01),while BS/BV,Tb.Sp and Tb.N were decreased(P＜0.05).The bone formation rate was higher(P＜0.01).Compared with both the control and treatment groups,the MIA group exhibited a significant increase in the number of osteoclasts in the subchondral bone(P＜0.01),along with a notable decrease in H-type blood vessels and OCN-positive areas(P＜0.01).Conclusion:Intra-articular injection of SHED-EXO can reg-ulate condylar subchondral bone homeostasis in TMJ OA of rats by promoting osteogenesis and inhibiting osteoclasts.

Kidney deficiency syndrome is a common clinical syndrome in traditional Chinese medicine （TCM）. With the progress of science and technology， clinical and animal experiments on kidney deficiency syndrome have made remarkable progress. Research on kidney deficiency and the nature of "kidney" involves a large number of physiological and pathological bases， which are closely related to physiological and pathological links in the human body， among which the neuroendocrine-immune network shares the closest relationship. However， there are still many challenges in modern research on kidney deficiency syndrome， such as expert consensus on clinical diagnostic criteria and evaluation indexes and optimization of animal experimental models. In the past decade， a large number of clinical and animal experiments have been reported in the literature on kidney deficiency syndrome， among which the literature focusing on the combination of disease and syndrome is predominant， and most of them focus on kidney Yang deficiency and kidney Yin deficiency， involving the exploration of many pathological mechanisms. Research on the mechanisms related to kidney deficiency syndrome encompasses multiple signaling pathways and various biochemical indicators， including the phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-erythroid 2-relatedfactor-2（PI3K/Akt/Nrf2） signaling pathway， the Toll-like receptor 4/myeloid differentiation factor88/nuclear factor-κB（TLR4/MyD88/NF-κB） signaling pathway， the Janus kinase 2/signal transducer and activator of transcription 3（JAK2/STAT3） signaling pathway， Osteoprotectin/nuclear factor-κB receptor activator ligand/receptor activator of nuclear factor-κB （OPG/RANKL/RANK） signaling pathway. The biochemical indicators cover the cyclic adenosine monophosphate/cyclic guanosine monophosphate （cAMP/cGMP） ratio， Na⁺-K⁺-ATPase activity， Ca²⁺-Mg²⁺-ATPase activity， adrenocorticotropic hormone （ACTH）， polycorticosterone （CORT）， 17-OHCS， and other sex hormone indicators， providing crucial reference values for diagnosing kidney Yang deficiency or kidney Yin deficiency. The literature related to kidney deficiency syndrome over the past decade was collated and excavated， with a view to providing a reference for research on kidney deficiency syndrome.

Blood deficiency syndrome (BDS) refers to a pathological state with blood dysfunction and organ dystrophy in traditional Chinese medicine. Danggui Wuji granules (DWG) was developed from a formula containing Angelicae Sinensis Radix and Musculus et Os Galli Domestici. Herein, we investigated the mechanism of DWG in treating BDS by modulating gut microbiota. We found that DWG protected mice from BDS by elevating the levels of red blood cell count, hemoglobin, and hematocrit in peripheral blood and increasing the erythrocyte membrane Na⁺-K⁺-ATPase activity. Danggui Wuji granules changed the composition and metabolites of colonic flora. Notably, Lactobacillus, Muribaculaceae, and Alistipes were the main genera showing changes after DWG treatment. Our findings revealed that DWG presented a positive therapeutic effect on BDS in mice by regulating the gut microbiota and metabolites. The protective mechanism of DWG was associated with pathways such as metabolic pathways, biosynthesis of secondary metabolites, ABC transporters, ribosome, thyroid hormone synthesis, lysine degradation, galactose metabolism, tyrosine metabolism, etc.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

ObjectiveTo clarify the therapeutic effect of Huashi Baidu prescription on pneumonia in mice caused by influenza A （H1N1） virus and explore its mechanism based on the transcriptome. MethodA mouse influenza viral pneumonia model was built by intranasal infection with influenza A virus， and mice were continuously administered the drug for five days， so as to investigate the general condition， lung index， viral load， pathological morphology of lung tissue， survival time， and prolongation rate of survival time of mice and clarify the therapeutic effect of Huashi Baidu prescription on influenza viral pneumonia. Transcriptome technology was used to detect the differentially expressed genes in the lung tissue of mice in the model group and the normal group， as well as the Huashi Baidu prescription group and the model group， and the potential core target of the Huashi Baidu prescription for the treatment of influenza viral pneumonia was screened. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to verify the effect of Huashi Baidu prescription on the mRNA expression level of core target genes. ResultCompared with the normal group， the lung index and viral load in the lung tissue of the model group were significantly increased （P<0.05， P<0.01）. Compared with the model group， the high-dose group of Huashi Baidu prescription significantly prolonged the survival time of mice infected with influenza A virus （P<0.05） and significantly reduced the lung index value of mice （P<0.05） and the viral load of lung tissue. The high-dose， medium-dose， and low-dose groups of Huashi Baidu prescription could significantly reduce lung tissue inflammation， blood stasis， swelling， and other pathological changes in mice （P<0.05， P<0.01）. Transcriptome analysis of lung tissue showed that core genes were mainly enriched in the nuclear transcription factor-κB （NF-κB） signaling pathway， interleukin-17 （IL-17） signaling pathway， cytokine-cytokine receptor interaction， and other pathways after the intervention of Huashi Baidu prescription. TRAF6， NFKBIA， CCL2， CCL7， and CXCL2 were the top five node genes with combined score values. Real-time PCR validation showed that Huashi Baidu prescription significantly downregulated the mRNA expression of key genes TRAF6 and NFKBIA in the NF-κB signaling pathway， as well as chemokines CCL2， CCL7， and CXCL2 （P<0.05， P<0.01）. ConclusionHuashi Baidu prescription has a therapeutic effect on influenza viral pneumonia， possibly by inhibiting the expression of key nodes TRAF6 and NFKBIA in the NF-κB signaling pathway and that of chemokines CCL2， CCL7， and CXCL2， reducing the recruitment of inflammatory cells and viral load， and exerting anti-influenza viral pneumonia effects.