The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

In this single-arm prospective cohort study, the aim was to evaluate the antihypertensive efficacy and safety of the angiotensinⅡreceptor-neprilysin inhibitor sacubitril/valsartan in patients with refractory hypertension (RH) undergoing peritoneal dialysis. A total of 67 peritoneal dialysis patients with regular treatment for ≥ 3 months and confirmed RH were enrolled. Sacubitril/valsartan was added to the background antihypertensive therapy and titrated according to a standardized protocol for 6 months. Data on RH control, demographic and clinical characteristics, and adverse reactions were collected before and after intervention. The mean values of valid 24 h ambulatory blood pressure recordings, nocturnal systolic blood pressure (SBP) dipping percentage, blood pressure variability parameters, and the blood pressure control rate were compared before and after treatment. Laboratory and clinical data were also compared. After a median follow-up of 8.0 (4.0, 12.5) months, 50 patients completed the study. After treatment, all blood pressure parameters significantly decreased compared with baseline. The mean values of valid 24 h SBP decreased by 9.52 mmHg ( t=4.79, P<0.001) and the mean values of valid 24 h diastolic blood pressure (DBP) decreased by 7.55 mmHg ( t=5.90, P<0.001). Day-time SBP decreased by 10.82 mmHg ( t=5.22, P<0.001) and day-time DBP by 8.41 mmHg ( t=6.28, P<0.001). Night-time SBP decreased by 6.93 mmHg ( t=2.81, P=0.007) and night-time DBP by 4.95 mmHg ( t=3.12, P=0.003). The standard deviation (SD) of 24 h-SBP ( t=2.43, P=0.018), 24 h DBP-SD ( t=3.82, P<0.001), day-time DBP-SD ( t=2.80, P=0.007), and the coefficient of variation of 24 h-DBP ( t=2.04, P=0.046) were significantly reduced. The blood pressure control rate increased from 14.90% to 44.80% ( χ2=12.89, P<0.001). During follow-up, no patient experienced acute deterioration of renal function. One case of hyperkalemia returned to normal after appropriate treatment, and no serious adverse events occurred. These findings suggest that sacubitril/valsartan effectively lowers blood pressure and improves the blood pressure control rate in peritoneal dialysis patients with RH, with favorable safety and tolerability.

Stiff person syndrome (SPS) is a rare neuro-immune disorder characterized by exaggerated startle responses and muscle spasms in response to minor stimuli. SPS is often misdiagnosed as panic disorder or agoraphobia. This paper reported a case of a patient with SPS presenting symptoms similar to panic attack. The patient had been misdiagnosed as dystonia, anxiety disorder and panic attack. The patient was finally correctly diagnosed through multiple disciplinary team discussions. This study integrates a comprehensive understanding of symptomatology and patient-reported experiences with targeted neurological evaluations and supplementary diagnostic tools to improve the accuracy of etiological diagnoses. This study aims to enhance the ability of psychiatrists to recognize somatic diseases presenting with psychiatric symptoms and to improve clinical diagnostic and treatment levels.

It is believed that Shengyang Yiwei Decoction （升阳益胃汤， SYD） is effective in regulating the flow of Qi （气）， and can treat various diseases caused by the disorder of the spleen and stomach Qi. In clinical practice， based on the pathological characteristics of children often having insufficient spleen， and adhering to the principle of treating different diseases with the same method， the focus is placed on the core pathogenesis of spleen and stomach Qi disharmony. We use SYD in various pediatric conditions such as allergic rhinitis， post COVID-19 condition， urethral syndrome， and dysfunctional uterine bleeding in adolescence， and emphasize the treatment is flexibly tailored to the symptoms.

BACKGROUND:During bone tissue healing,promoting the vascularization of new bone is a common strategy to accelerate the repair of bone tissue.However,the rapid fibrosis process during bone defect repair is often ignored.OBJECTIVE:To design and prepare a core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus,characterize physical characteristics of the scaffold,and verify the anti-fibrosis and osteogenic properties in vitro and in vivo.METHODS:A core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus was designed and prepared.The outer shell structure of the scaffold was composed of polycaprolactone electrospun nanofibers loaded with fibroblast activating protein inhibitor;and the inner core structure was composed of gelatin methacrylate hydrogel loaded with deferoxamine.The physical characteristics of electrospun and hydrogel were characterized,and the biocompatibility of the material was verified by live-dead staining and CCK-8 assay.The antifibrotic effect of core-shell structure was analyzed by fibroblast in vitro assay.The osteogenic effect of fibroblast activating protein inhibitor in core-shell structure was analyzed by MC3T3-E1 cells in vitro assay.The vasogenic effect of deferoxamine in core-shell structure was analyzed by human umbilical vein endothelial cells.The effect of bionic core-shell scaffold on bone repair was evaluated by critical bone defect test in rats.RESULTS AND CONCLUSION:(1)The core-shell structure bionic scaffold had good biocompatibility.Hydrophobic polycaprolactone electrospun fibers prepared by electrospinning technology could effectively block the ingrowth of exogenous fibrous tissue on the physical level.The electrospun fiber membrane could effectively release the anti-fibrosis drug fibroblast activating protein inhibitor within 2 weeks,and the released anti-fibrosis drug could inhibit the growth and adhesion of fibroblasts around bone defects,effectively reduced the expression of fibroblast-related proteins,promoted the expression of osteoblast protein in MC3T3-E1 cells,and accelerated its mineralization rate.The deferoxamine in the core-shell structure could promote the migration and vascular formation ability of human umbilical vein endothelial cells,and promoted their strong expression of"H"vascular characteristic protein.(2)In critical bone defect model of SD rats established in the femur,compared with polycaprolactone membrane,the core-shell structure bionic scaffold could effectively repair bone defects.(3)These findings indicate that the core-shell structure bionic scaffold can prevent excessive fibrosis of callus and promote the formation of"H"vessels in the new callus,which can effectively avoid the occurrence of nonunion and accelerate the repair process of critical bone defect.

BACKGROUND:Cell senescence is one of the major risk factors for osteoarthritis,but there is no widely accepted anti-osteoarthritis therapy targeting senescent cells.OBJECTIVE:To develop a feasible treatment strategy targeting senescent cells in osteoarthritis.METHODS:The cationic liposome containing rapamycin,RAPA@Lipo,was prepared by thin film dispersion method.Methylallylated hyaluronic acid hydrogel was synthesized,and RAPA@Lipo was added to the methylallylated hyaluronic acid hydrogel aqueous phase solution.The hydrogel microspheres were prepared by microfluidic equipment.Solid hydrogel microspheres(RAPA@Lipo@MS)were crosslinked under violet light.Primary human chondrocytes were co-cultured with RAPA@Lipo and RAPA@Lipo@MS,respectively.The biocompatibility of the materials was evaluated by CCK-8 assay and live/dead staining.Primary rat chondrocytes were cultured in four groups.Normal control group was cultured for 48 hours.The model group was stimulated with H2O2 for 24 hours to establish senescent cell model.RAPA@Lipo group and RAPA@Lipo@MS group were cultured for 24 hours after establishing senescent cell model with RAPA@Lipo and RAPA@Lipo@MS,respectively.After culture,immunofluorescence was used to observe the expression of p62 and type Ⅱ collagen.RT-PCR was used to detect the mRNA expression of interleukin 6,matrix metalloproteinase 13,type Ⅱ collagen,aggrecan,and ADAMTS-5.RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead staining showed that RAPA@Lipo and RAPA@Lipo@MS had good biocompatibility.(2)Compared with the normal control group,the protein expression of p62 was increased(P<0.05);the expression of type Ⅱ collagen was decreased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were increased(P<0.05);mRNA expression levels of type Ⅱ collagen and aggrecan were decreased(P<0.05)in the model group.Compared with the model group,the expression of p62 protein was decreased(P<0.05);the expression of type Ⅱ collagen was increased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were decreased(P<0.05);mRNA expression of type Ⅱ collagen and aggrecan increased(P<0.05)in the RAPA@Lipo@MS group.(3)These findings indicate that RAPA@Lipo@MS can control the quality of cells in vivo by enhancing autophagy,reduce senescent cells in vivo,and locally eliminate senescent cells and senescence-associated secretory phenotype factors in osteoarthritis,thereby slowing the progression of osteoarthritis and creating a cartilage microenvironment that promotes regeneration.

Objective To investigate the clinical efficacy of fire dragon pot comprehensive therapy in patients with knee paralysis due to liver and kidney deficiency following total knee arthroplasty(TKA).Methods A total of 114 patients undergoing unilateral TKA were randomly assigned to two groups using a random number table.The control group(n=57)received standard enhanced recovery after surgery(ERAS)nursing care,while the intervention group(n=57)received high-frequency general massage(HGM)therapy in addition to the standard ERAS protocol.Outcomes including visual analogue scale(VAS)scores,Hamilton Anxiety Scale(HAMA)scores,Hospital for Special Surgery(HSS)knee scores,and serum levels of inflammatory markers[C-reactive protein(CRP),neutrophil count(NE),and lymphocyte count(LY)]were compared between the two groups.Results Compared with the control group,the intervention group exhibited significantly lower VAS scores at 3 days postoperatively and at discharge,reduced HAMA scores from the preoperative period through 3 days after surgery,improved HSS scores[specifically in pain,function,range of motion,stability,and total score]at 2 weeks postoperatively,and more pronounced improvements in inflammatory markers,including lower levels of CRP and NE and higher LY levels(all P<0.05).Conclusion The comprehensive moxibustion therapy using Huolongjar effectively alleviates postoperative pain following TKA,enhances joint function,reduces anxiety levels,and mitigates inflammatory responses.This intervention is safe,simple to administer,and holds promise for clinical application and wider dissemination.

Objective To investigate the clinical efficacy of fire dragon pot comprehensive therapy in patients with knee paralysis due to liver and kidney deficiency following total knee arthroplasty(TKA).Methods A total of 114 patients undergoing unilateral TKA were randomly assigned to two groups using a random number table.The control group(n=57)received standard enhanced recovery after surgery(ERAS)nursing care,while the intervention group(n=57)received high-frequency general massage(HGM)therapy in addition to the standard ERAS protocol.Outcomes including visual analogue scale(VAS)scores,Hamilton Anxiety Scale(HAMA)scores,Hospital for Special Surgery(HSS)knee scores,and serum levels of inflammatory markers[C-reactive protein(CRP),neutrophil count(NE),and lymphocyte count(LY)]were compared between the two groups.Results Compared with the control group,the intervention group exhibited significantly lower VAS scores at 3 days postoperatively and at discharge,reduced HAMA scores from the preoperative period through 3 days after surgery,improved HSS scores[specifically in pain,function,range of motion,stability,and total score]at 2 weeks postoperatively,and more pronounced improvements in inflammatory markers,including lower levels of CRP and NE and higher LY levels(all P<0.05).Conclusion The comprehensive moxibustion therapy using Huolongjar effectively alleviates postoperative pain following TKA,enhances joint function,reduces anxiety levels,and mitigates inflammatory responses.This intervention is safe,simple to administer,and holds promise for clinical application and wider dissemination.

BACKGROUND:During bone tissue healing,promoting the vascularization of new bone is a common strategy to accelerate the repair of bone tissue.However,the rapid fibrosis process during bone defect repair is often ignored.OBJECTIVE:To design and prepare a core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus,characterize physical characteristics of the scaffold,and verify the anti-fibrosis and osteogenic properties in vitro and in vivo.METHODS:A core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus was designed and prepared.The outer shell structure of the scaffold was composed of polycaprolactone electrospun nanofibers loaded with fibroblast activating protein inhibitor;and the inner core structure was composed of gelatin methacrylate hydrogel loaded with deferoxamine.The physical characteristics of electrospun and hydrogel were characterized,and the biocompatibility of the material was verified by live-dead staining and CCK-8 assay.The antifibrotic effect of core-shell structure was analyzed by fibroblast in vitro assay.The osteogenic effect of fibroblast activating protein inhibitor in core-shell structure was analyzed by MC3T3-E1 cells in vitro assay.The vasogenic effect of deferoxamine in core-shell structure was analyzed by human umbilical vein endothelial cells.The effect of bionic core-shell scaffold on bone repair was evaluated by critical bone defect test in rats.RESULTS AND CONCLUSION:(1)The core-shell structure bionic scaffold had good biocompatibility.Hydrophobic polycaprolactone electrospun fibers prepared by electrospinning technology could effectively block the ingrowth of exogenous fibrous tissue on the physical level.The electrospun fiber membrane could effectively release the anti-fibrosis drug fibroblast activating protein inhibitor within 2 weeks,and the released anti-fibrosis drug could inhibit the growth and adhesion of fibroblasts around bone defects,effectively reduced the expression of fibroblast-related proteins,promoted the expression of osteoblast protein in MC3T3-E1 cells,and accelerated its mineralization rate.The deferoxamine in the core-shell structure could promote the migration and vascular formation ability of human umbilical vein endothelial cells,and promoted their strong expression of"H"vascular characteristic protein.(2)In critical bone defect model of SD rats established in the femur,compared with polycaprolactone membrane,the core-shell structure bionic scaffold could effectively repair bone defects.(3)These findings indicate that the core-shell structure bionic scaffold can prevent excessive fibrosis of callus and promote the formation of"H"vessels in the new callus,which can effectively avoid the occurrence of nonunion and accelerate the repair process of critical bone defect.

BACKGROUND:Cell senescence is one of the major risk factors for osteoarthritis,but there is no widely accepted anti-osteoarthritis therapy targeting senescent cells.OBJECTIVE:To develop a feasible treatment strategy targeting senescent cells in osteoarthritis.METHODS:The cationic liposome containing rapamycin,RAPA@Lipo,was prepared by thin film dispersion method.Methylallylated hyaluronic acid hydrogel was synthesized,and RAPA@Lipo was added to the methylallylated hyaluronic acid hydrogel aqueous phase solution.The hydrogel microspheres were prepared by microfluidic equipment.Solid hydrogel microspheres(RAPA@Lipo@MS)were crosslinked under violet light.Primary human chondrocytes were co-cultured with RAPA@Lipo and RAPA@Lipo@MS,respectively.The biocompatibility of the materials was evaluated by CCK-8 assay and live/dead staining.Primary rat chondrocytes were cultured in four groups.Normal control group was cultured for 48 hours.The model group was stimulated with H2O2 for 24 hours to establish senescent cell model.RAPA@Lipo group and RAPA@Lipo@MS group were cultured for 24 hours after establishing senescent cell model with RAPA@Lipo and RAPA@Lipo@MS,respectively.After culture,immunofluorescence was used to observe the expression of p62 and type Ⅱ collagen.RT-PCR was used to detect the mRNA expression of interleukin 6,matrix metalloproteinase 13,type Ⅱ collagen,aggrecan,and ADAMTS-5.RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead staining showed that RAPA@Lipo and RAPA@Lipo@MS had good biocompatibility.(2)Compared with the normal control group,the protein expression of p62 was increased(P<0.05);the expression of type Ⅱ collagen was decreased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were increased(P<0.05);mRNA expression levels of type Ⅱ collagen and aggrecan were decreased(P<0.05)in the model group.Compared with the model group,the expression of p62 protein was decreased(P<0.05);the expression of type Ⅱ collagen was increased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were decreased(P<0.05);mRNA expression of type Ⅱ collagen and aggrecan increased(P<0.05)in the RAPA@Lipo@MS group.(3)These findings indicate that RAPA@Lipo@MS can control the quality of cells in vivo by enhancing autophagy,reduce senescent cells in vivo,and locally eliminate senescent cells and senescence-associated secretory phenotype factors in osteoarthritis,thereby slowing the progression of osteoarthritis and creating a cartilage microenvironment that promotes regeneration.