Naturally derived metabolites are valuable resources for drug research and development, and play an important role in the treatment of diseases. As the "second genome" of the body, gut microbiota is rich in metabolic enzymes, which interacts with external substances such as drugs, thus affecting the progression of diseases. This article summarizes the interaction between gut microbiota-producing enzymes and natural medicines, and focuses on the impact of this interaction on disease progression, hoping to provide new ideas for the development and pharmacological mechanism of natural medicines.

Objective To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty(TKA).Methods From February 2023 to July 2023,26 patients with unilateral knee osteoarthritis(KOA)were treated with TKA,including 4 males and 22 females,aged from 57 to 85 years old with an average of(67.58±6.49)years old;body mass in-dex(BMI)ranged from 18.83 to 38.28 kg·m-2 with an average of(26.43±4.15)kg·m-2;14 patients on the left side,12 pa-tients on the right side;according to Kellgren-Lawrence(K-L)classification,6 patients with grade Ⅲ and 20 patients with grade Ⅳ;the courses of disease ranged from 1 to 14 years with an average of(5.54±3.29)years.Images and videos of standing up and walking,walking side shot,squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation.The human posture estimation framework OpenPose were used to analyze stride frequency,step length,step length,step speed,active knee knee bending angle,stride length,double support phase time,as well as maximum hip flexion angle and maximum knee bending angle on squatting position.Western Ontario and McMaster Universities(WOMAC)arthritis index and Knee Society Score(KSS)were used to evaluate clinical efficacy of knee joint.Results All patients were followed up for 5 to 7 weeks with an average of(6.00±0.57)weeks.The total score of WOMAC decreased from(64.85±11.54)before op-eration to(45.81±7.91)at 6 weeks after operation(P＜0.001).The total KSS was increased from(101.19±9.58)before opera-tion to(125.50±10.32)at 6 weeks after operation(P＜0.001).The gait speed,stride frequency and stride length of the affected side before operation were(0.32±0.10)m·s-1,(96.35±24.18)steps·min-1,(0.72±0.14)m,respectively;and increased to(0.48±0.11)m·s 1,(104.20±22.53)steps·min-1,(0.79±0.10)m at 6 weeks after operation(P＜0.05).The lower limb support time and active knee bending angle decreased from(0.31±0.38)sand(125.21±11.64)° before operation to(0.11±0.04)s and(120.01±13.35)° at 6 weeks after operation(P＜0.05).Eleven patients could able to complete squat before operation,13 patients could able to complete at 6 weeks after operation,and 9 patients could able to complete both before operation and 6 weeks after operation.In 9 patients,the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation,and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation.Conclusion Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of pa-tients'gait.Knee pain of KOA was relieved and the function was improved,the supporting ability of the affected limb was im-proved after TKA,and the patient's stride frequency,stride length and stride speed were improved,and the overall movement rhythm of both lower limbs are more coordinated.

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

ObjectiveTo investigate the analgesic action and mechanism of intrathecal 2R， 6R-hydroxynorketamine （2R， 6R-HNK） on spared nerve injury （SNI）-induced chronic neuropathic pain （CNP） in female mice. MethodsSNI was used to establish acute and chronic CNP models in female mice. The mice were randomly divided into different groups with administration of vehicle， 2R， 6R-HNK or S-ketamine （10 mg/kg intraperitoneal injection/i.p. or 7， 21 μmol/L intrathecal injection/i.t.） at 3 weeks after or 30 min/1 d before operation （n = 3 - 7 mice/group）. The curative or preventive effect of 2R， 6R-HNK was evaluated by mechanical paw withdrawal threshold （PWT） and the analgesic efficiency. Finally， immunofluorescence and RT-PCR of dorsal root ganglion （DRG） and spinal dorsal horn （SDH） were used to explore the possible mechanisms. ResultsCompared with vehicle， intrathecal injection of 2R， 6R-HNK largely reversed SNI-induced bilateral mechanical allodynia in a delayed-and-dose-dependent way. Among them， 21 μmol/L 2R， 6R-HNK reached its maximum analgesic efficiency （75.32±7.69） % at 2 d. Pre-intrathecal delivery of 2R， 6R-HNK also delayed the development of bilateral mechanical hypersensitivity 2 - 3 d induced by SNI. Mechanically， 2R， 6R-HNK reversed not only the abnormal excitability of neurons in bilateral DRG and superficial SDH， but also the upregulation of calcitonin gene-related peptide （CGRP） and brain-derived nerve growth factor （BDNF） in DRG. ConclusionIntrathecal administration of 2R， 6R-HNK exerts an analgesic effect against CNP， probably via suppressing abnormal neuronal excitability in ascending pain pathway as well as down-regulating CGRP and BDNF expression in DRG neurons.

BACKGROUND: The molecular mechanisms of heart failure (HF) are still poorly understood. Circular RNA (circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more about the potential roles of circRNAs in HF. METHODS & RESULTS: We used RNA sequencing data to identify the characteristics of circRNAs expressed in the heart and discovered that the majority of circRNAs screened were less than 2000 nt. Additionally, chromosomes One and Y had the most and least number of circRNAs, respectively. After excluding duplicate host genes and intergenic circRNAs, a total of 238 differentially expressed circRNAs (DECs) and 203 host genes were discovered. However, only four of the 203 host genes of DECs were examined in HF differentially expressed genes. Another study used Gene Oncology analysis of DECs host genes to elucidate the underlying pathogenesis of HF, and it found that binding and catalytic activity accounted for a large portion of DECs. Immune system, metabolism, and signal transduction pathways were significantly enriched. Furthermore, 1052 potentially regulated miRNAs from the top 40 DECs were collected to build a circRNA-miRNA network, and it was discovered that 470 miRNAs can be regulated by multiple circRNAs, while others are regulated by a single circRNA. In addition, a comparison of the top 10 mRNAs in HF and their targeted miRNAs revealed that DDX3Y and UTY were regulated by the most and least circRNA, respectively. CONCLUSION These findings demonstrated circRNAs have species and tissue specific expression patterns; while circRNA expression is independent on host genes, the same types of genes in DECs and DEGs worked in HF. Our findings would contribute to a better understanding of the critical roles of circRNAs and lay the groundwork for future studies of HF molecular functions.

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

BACKGROUND: Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate. OBJECTIVE: To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis. METHODS: Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I² statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I²=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I²=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I²=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I²=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence. CONCLUSION Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430).
Pregnancy ; Female ; Humans ; Live Birth ; Fertilization in Vitro/methods* ; Pregnancy Outcome ; Abortion, Spontaneous ; Acupuncture 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 explore the feasibility and accuracy of sex determination by morphology of the distal humerus in North China population. Methods Observing sexually dimorphic differences of olecranon fossa shape, trochlear symmetry, trochlear constriction and angle of medial epicondyle. Each characteristic was divided into three categories: male, unknown and female. The morphological characteristics of the humerus of 70 individuals (35 males and 35 females) from the Ming and Qing Dynasties in North China were counted to compare the occurrence rate of different categories of distal humeral morphology and the accuracy rate of sex determination. Results There were statistically significant differences in the performance of the four traits of the distal humerus between males and females. The accuracy rate of angle of medial epicondyle was the highest at 76%, while the lowest accuracy rate of trochlear constriction was only 52%. The accuracy of the combined four traits was higher than the single ones, with an accuracy rate of 76% (83% for males and 68% for females). Conclusion Distal humerus morphology can be used to determine sex when skulls and pelvis are absent.

Mitosis is important for cell proliferation in eukaryotes, and chromosome replication and accurate separation are essential for cell division. Supervillin is a membrane and microfilament actin binding protein. Previous studies have found that it regulates the dynamic changes of the cortical distribution of F-actin and myosin II in cytokinesis, thus ensuring the correct distribution of the contraction ring and participating in the final completion of cytoplasm divisions. But it is not clear whether it functions during metaphase. Supervillin has several splicing isomers, among which supervillin isoform 4 (SV4) is the largest splicing isomer. In this study, the expression of SV4 in cells was reduced by the RNA interference method, and the dynamic process of mitosis and the morphology of astral spindles were detected and observed by real-time microscopy and immunofluorescence staining, and the potential molecular mechanism of SV4 in mitosis was analyzed. The results showed abnormal cell divisions after SV4 reduction: delayed transition from metaphase to anaphase (P<0.001), abnormal assembly of microtubules, a twofold-increase of the number of cells with multipolar spindles, and decreased γ-tubulin signaling in the centrosome (P<0.001). Through GST pull-down and mass spectrometry experiments, we found that SV4 and Aurora A bind to each other, and SV4 regulates the localization and activation of Aurora A in the centrosome during mitosis. In summary, supervillin plays an important role in mitosis. The isomer SV4 regulates spindle integrity and γ-tubulin recruitment by interacting with Aurora A and recruiting it for proper localization and activation in the centrosome during the metaphase, thus promoting the correct assembly of bipolar spindles and ensuring the accurate separation of chromosomes and the smooth progress of mitosis.