Xiaoyaowan has the effects of soothing the liver， invigorating the spleen， regulating menstruation， and nourishing blood. It is often used to treat the distending pain of the chest and hypochondriac， loss of appetite， dizziness， and irregular menstruation caused by liver depression and spleen deficiency. The formula originated from the Sinisan of Treatise on Cold Damage（《伤寒论》） in the Han dynasty and was officially formulated in the Song dynasty's Taiping Royal Prescriptions（《太平惠民合计局方》）. In the Ming and Qing dynasties， it was developed into more comprehensive formulas such as modified Bazhentang， modified Xiaoyaowan， and other formulas. In recent years， Xiaoyaowan has become a classic formula for treating many symptoms of liver depression. The Pharmacopoeia of the People's Republic of China（《中华人民共和国药典》）， 2020 edition， records Xiaoyaowan and modified Xiaoyaowan. Modern clinical research has further expanded the therapeutic range of this formula. Through literature research， it is found that there are certain reports on the clinical application and quality analysis of Xiaoyaowan， but the relevant literature lacks collation so far. Therefore， relevant literature was consulted and sorted out. The paper summarized the treatment of mammary hyperplasia， depression， irregular menstruation， melasma， menopausal syndrome， and polycystic ovary syndrome with Xiaoyaowan， as well as the quality analysis of paeoniflorin， ferulic acid， and glycyrrhizinic acid of Xiaoyaowan. It is expected to lay a foundation for further research on clinical application， pharmacodynamic mechanism， and quality control of this classic formula.

By sorting out the differences and connections between family doctor teams and specialized disease teams, role competency and mutual collaboration, and introducing the learning health system (LHS) mechanism, a comprehensive operating system for community general practice learning organizations based on LHS was constructed, focusing on five single disease types. The system includes a combination of general and specialized medicine that links three levels of medical institutions, thereby opening up the business cooperation process between professionals in different institutions, and establishing a sustainable collaboration mechanism. This allows medical institutions at three levels to continuously tap the potential of their disciplines, achieve their own ability growth and feel higher work value, and also bring better health solutions to residents, guided by the common goal of "health centered, patient centered".

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objectives:To retrieve,evaluate and summarize the contemporary evidence of strategies for weaning from extracorporeal membrane oxygenation(ECMO)of adult patients,and to provide evidence-based reference for clinical practice. Methods:The Web of Science,Embase,Cochrane Library,PubMed,Wanfang Database,CNKI,VIP website,SinoMed,BMJ Best Practice,National Institute for Health and Care Excellence,Joanna Briggs Institute Library,UpToDate and the website of Agency for Healthcare Research and Quality,Society of Critical Care Medicine,American Association of Critical-Care Nurses,European Society of Intensive Care Medicine and Extracorporeal Life Support Organization were researched to collect the literature related to randomized controlled trials,systematic reviews,guidelines,evidence summaries,expert consensuses and clinical decisions in this field.The time limit for the retrieval is from the inception of databases until July 2023. Results:A total of 13 related literature were retrieved,including 4 guidelines,4 expert consensuses,3 clinical decisions and 2 system reviews.Totally 42 evidences were formulated based on retrieved literature,including adequately accessing the ability of gas exchange before weaning from veno-venous ECMO(V-V ECMO)and withdrawing from veno-arterial ECMO(V-A ECMO)as soon as possible when patients's heart function has recovered,involving six aspects such as team composition,anticoagulation measures,assessment before weaning,weaning implementation,cannula and wound management and quality measures. Conclusions:It is suggested to build a professional ECMO team based on the actual hospital situation,to follow the contemporary evidence to standardize the weaning process of patients from ECMO to ensure the patients'safety and improve the outcomes.

Objective To construct a model of Fat-1/APPPS1 transgenic mice and a cellular model of microglia and explore the improvement effect and underlying mechanism of n-3 polyunsaturated fatty acids(n-3 PUFAs)on the learning and memory abilities of APPPS1 mice by regulating microglial activation and polarization.Methods After the male mice with heterozygous Fat-1 genotype were mated with the female ones with heterozygous APPPS1 genotype,genetic identification was used to screen the male offspring with Fat-1/APPPS1 genotype.Then after the male wild-type(WT)mice and those with Fat-1,Fat-1/APPPS1,and APPPS1 genotypes were bred until 9 months old,their learning and memory abilities were evaluated with Morris water maze(MWM)test.In addition,gas chromatography-mass spectrometry(GC-MS)was performed to detect the concentration of PUFAs in the brain,and immunohistochemistry(IHC)was applied to detect the deposition of β-amyloid protein(Aβ)in the hippocampal regions.Moreover,immunofluorescence assay,qRT-PCR,and enzyme-linked immunosorbent assays(ELISA)were conducted to measure inflammation,and transcription and expression of Iba-1(indicating the microglial activation)and CD86 and CD206(indicating microglial polarization)in central nervous system(CNS).After pretreated with DHA+EPA(25 pmol/mL∶25 μmol/mL),microglial model of inflammatory injury was established in immortalized mouse BV2 cells induced by LPS(1 μg/mL).Afterwards,immunofluorescence assay,qRT-PCR and Western blotting were used to detect inflammation and microglial activation and polarization.Results Compared with the APPPS1 mice,endogenous n-3 PUFAs effectively improved the learning and memory disorders in Fat-1/APPPS1 ones(P＜0.05),remarkably alleviated Aβ deposition in the hippocampal regions(P＜0.05),evidently reduced CNS inflammation and microglial activation(P＜0.05)and transformed the activated microglia from M1 to M2(P＜0.05).Furthermore,BV2 cells with DHA+EPA pretreatment obviously resisted LPS-induced cellular inflammation and induced activated ones from M1 to M2(P＜0.05).Conclusion n-3 PUFAs inhibit the microglial activation,regulate the microglial polarization from M1 to M2,reduce CNS inflammation,and thus alleviate learning and memory disorders in APPPS1 mice.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.
Humans ; Middle Aged ; Aged ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Prospective Studies ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

OBJECTIVE: To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine (Aza), including standard dose (standard dose group) and low-dose long-term (adjusted dose group), in the treatment of elderly acute myeloid leukemia (AML). METHODS: A total of 103 elderly patients with AML (non-acute promyelocytic leukemia) from January 2020 to June 2021 were enrolled. Aza was administered at the standard dose of 75 mg/(m²·d) for 7 days in the standard dose group (50 cases), while at 100 mg/d for 7-12 days in the adjusted dose group (53 cases). The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment. The efficacy and safety between standard dose group and adjusted dose group were compared. Subgroup analysis were performed in the two groups for Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy for efficacy and safety. RESULTS: There were no significant differences in overall response rate (ORR), incidence of adverse reaction, and 1-year overall survival (OS) rate between standard dose group and adjusted dose group (P >0.05). The ORR of combination was higher than that of Aza alone (P < 0.05), while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy (P >0.05). The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone. There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone (P <0.05). No significant difference was observed in 1-year OS between Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy (P >0.05). CONCLUSIONS Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety. Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions, and may not result in longer survival compared with Aza alone. Aza combined with BCL-2 inhibitor not only has similar effect in complete remission, objective response rate, and OS compared with Aza combined with low-dose chemotherapy, but also has higher safety.
Humans ; Aged ; Azacitidine/therapeutic use* ; Prospective Studies ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols ; Leukemia, Myeloid, Acute/etiology* ; Proto-Oncogene Proteins c-bcl-2

Objective To study topological structure of a new type of three-dimensional (3D) printed height increasing insoles for leg length discrepancy (LLD) and its effect on biomechanics of lower limbs. Methods Topological structure for middle and rear part of the insole was optimized by solid isotropic microstructures with penalization (SIMP), the force was loaded and the boundary conditions were set according to force area of the insole, and the height increasing insole with thermoplastic polyurethanes (TPU) materials was printed by selected laser sintering (SLS). The insoles were used in 9 patients with LLD, visual analogue scale (VAS) and Maryland foot function scores were used to compare pain and foot function changes of patients before and after using the insole, and the 3D gait analysis system was used to compare spatiotemporal parameters and vertical ground reaction force (vGRF) of both lower limbs. Result sAfter the patient wore 3D printed insole, VAS scores decreased, Maryland foot function scores increased, vGRF of both lower limbs decreased, and the difference of cadence, stance phase and swing phase in both lower limbs decreased. Conclusions The 3D printed height increasing insole after topology optimization can improve coordination of lower limb movement, reduce ground impact, relieve pain and improve foot function, thus providing an effective personalized orthopedic plan for LLD treatment in clinic.

Objective: To investigate the correlation between body composition and eating habits among medical students, and to provide evidence for health promotion. Methods: In December 2021, stratified cluster random sampling method was used to conduct a questionnaire survey and body composition assessment among 445 students in grade one to grade four in Jining Medical University. Results: There were 152 girls (53.3%) and 45 boys (28.1%) with low skeletal muscle mass. Totally 167 students ( 37.5% ) had lower muscle mass, including 115 females (40.4%) and 49 males (30.6%). High body fat percentage was found in 259 (58.2%) students, including 179 females (62.8%) and 80 males (50.0%). There were 192 students (43.1%) with abnormal waist to hip ratio, with 139 females (48.8%) and 53 males (33.1%). In addition, emotional eating score of female students was significantly higher than that of male students(6.85±2.24, 6.11±2.69, t =2.96, P <0.05). Cognitive restricted eating was positively correlated with skeletal muscle mass and musde mass( r=0.13, 0.13, P <0.05). Emotional eating was positively correlated with body fat percentage, body fat and waist hip ratio( r =0.20, 0.20, 0.16, P <0.05). Unrestricted eating was positively correlated with body fat percentage, body fat and waist hip ratio( r =0.15, 0.18, 0.15, P <0.05). Multiple linear regression analysis showed that gender, family residence, physical activity and cognitive eating were associated with skeletal muscle mass and muscle mass of medical students( P <0.05). Conclusion With low skeletal muscle mass, low muscle mass, body fat percentage and waist and hip high ratio, reasonable eating habits combined with resistance exercise should be adopted to improve their physical health.