Loss of UBE2S causes meiosis I arrest with normal spindle assembly checkpoint dynamics in mouse oocytes.

The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.

Regulation of AR mRNA translation in response to acute AR pathway inhibition.

We report a new mechanism of androgen receptor (AR) mRNA regulation and cytoprotection in response to AR pathway inhibition (ARPI) stress in prostate cancer (PCA). AR mRNA translation is coordinately regulated by RNA binding proteins, YTHDF3 and G3BP1. Under ambient conditions m6A-modified AR mRNA is bound by YTHDF3 and translationally stimulated, while m6A-unmodified AR mRNA is bound by G3BP1 and translationally repressed. When AR-regulated PCA cell lines are subjected to ARPI stress, m6A-modified AR mRNA is recruited from actively translating polysomes (PSs) to RNA-protein stress granules (SGs), leading to reduced AR mRNA translation. After ARPI stress, m6A-modified AR mRNA liquid-liquid phase separated with YTHDF3, while m6A-unmodified AR mRNA phase separated with G3BP1. Accordingly, these AR mRNA messages form two distinct YTHDF3-enriched or G3BP1-enriched clusters in SGs. ARPI-induced SG formation is cell-protective, which when blocked by YTHDF3 or G3BP1 silencing increases PCA cell death in response to ARPI stress. Interestingly, AR mRNA silencing also delays ARPI stress-induced SG formation, highlighting its supportive role in triggering this stress response. Our results define a new mechanism for stress adaptive cell survival after ARPI stress involving SG-regulated translation of AR mRNA, mediated by m6A RNA modification and their respective regulatory proteins.

Psychometric soundness and predictive factors of the NCAST Parent-Child Interaction Teaching Scale in urban Chinese population.

BACKGROUND: Quality of parent-child interaction in early childhood functions as a critical indicator of nurturing care and is strongly associated with short-term and long-term development (health, cognition, language, social emotion, well-being, etc.). NCAST PCI Teaching Scale (PCI-TS), a video-based assessment regarded as a gold standard to measure PCI, has been widely used worldwide. However, its psychometric soundness among the urban Chinese population is unclear. This study assesses the PCI-TS's reliability and validity and explores predictive factors among urban Chinese parent-child dyads. METHODS: PCI-TS was adopted to code mother-child interaction among urban Chinese dyads recruited during the children's regular health checks in local maternal and child health centres. Reliability was evaluated by internal consistency (Cronbach'α coefficient) and test-retest reliability (Pearson correlation) with an average interval of 18 days. Score distribution of each subscale and total scale were compared with NCAST Database and Canadian community sample by single sample t-test. Criteria-related validity was conducted by Infant-Toddler Home Observation Measurement of the Environment (Pearson correlation). Predictive factors was performed by multiple linear regression. RESULTS: Four hundred and twenty-nine eligible mother-child dyads were included for data analysis among the 466 recruited samples. Four qualified local paediatricians accomplished video coding with an average agreement of 86%. The PCI-TS has strong reliability among the Chinese population with the Cronbach'α coefficients of the Caregiver-Infant total score, Caregiver total and Infant total scores of 0.81, 0.81 and 0.74, respectively; an acceptable test-retest reliability (r = 0.73, p < 0.01); and moderate correlation with IT-HOME, ranging from 0.53 to 0.62. Child age, birth weight, maternal education, full-time housewife, living with grandparent(s) and living space were predictive factors on PCI-TS in the Chinese population. CONCLUSION: PCI-TS showed good psychometric properties for measuring mother-child interactions among urban Chinese dyads, offering clinicians and researchers a practical tool to evaluate PCI objectively. Child age, maternal education and living space were beneficial factors, while full-time mothers and living with grandparent(s) were risk factors.

[Clinical study of Bushen Culuan Formula in treatment of ovulatory disorder infertility caused by hyperprolactinemia].

This paper aims to study the therapeutic effect and safety of Bushen Culuan Formula in the treatment of patients with infertility caused by hyperprolactinemia. Sixty patients with infertility caused by hyperprolactinemia of kidney deficiency and blood stasis were divided into the treatment group(Bushen Culuan Formula + Bromocriptine Mesylate Tablets placebo) and the control group(Bromocriptine Mesylate Tablets + Bushen Culuan Formula placebo), and ovulation rate, pregnancy rate, serum sex hormones, basal body temperature(BBT), and traditional Chinese medicine(TCM) symptom scores were observed. The results showed the clinical effective rate was 90.00% in the treatment group and 80.00% in the control group. The treatment group was able to significantly reduce the PRL level and increase the pregnancy rate, and it was superior to the control group in increasing the BBT biphasic ratio, improving the TCM symptom scores, and enhancing the ovulation rate. The results show that Bushen Culuan Formula is safe and reliable in treating ovulatory disorder infertility caused by hyperprolactinemia, with remarkable effects.

[Study on mechanism of regulation of sex hormones in treatment of hyperprolactinemia-induced ovulatory disorder infertility with Bushen Culuan Formula].

Transcriptomics was used to investigate the mechanism of action of Bushen Culuan Formula in the treatment of infertility caused by hyperprolactinemia(HPRL), and animal experiments were carried out to verify the results. After establishing an animal model of HPRL-induced infertility, the mice were divided into normal group, model group, Bushen Culuan Formula groups with high-, medium-, and low-doses, and bromocriptine group, and they were observed in terms of the estrous cycle, gonadal index, serum sex hormones, morphology of ovary and mammary gland, follicle count, and fertility. The results showed that the Bushen Culuan Formula could effectively restore the estrous cycle, down-regulate the levels of prolactin(PRL), follicle-stimulating hormone(FSH), and luteinizing hormone(LH), up-regulate the level of estradiol(E_2), increase the number of primordial follicles and sinus follicles, and improve the ovulation rate and fertility of mice. Through RNA sequencing combined with biosignature analysis, Bushen Culuan Formula may regulate the metabolism of lipids, antioxidant enzymes, and other substances in the cells of the ovary and pituitary gland through the signaling pathways of cAMP-PKA, Kiss-1/GPR54, and Hippo and exert therapeutic effects. The results of animal experiments showed that Bushen Culuan Formula could up-regulate serum dopamine(DA) level and pituitary DRD2 expression, down-regulate hypothalamus and ovary cAMP levels, as well as protein expressions of the pituitary gland and ovary PKA, CREB, and p-CREB, and treat HPRL-induced infertility by regulating the cAMP-PKA signaling pathway.

[Bushen Culuan Formula in treatment of infertility caused by polycystic ovary syndrome].

This study aims to observe the efficacy and safety of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS) and to explore the mechanism using metabolomics. Ninety-four patients with infertility caused by PCOS with the syndrome of kidney deficiency and blood stasis were selected and assigned into treatment and control groups(n=47). The basal body temperature(BBT) was measured, and B-ultrasonography was employed to monitor follicles, ovarian volume, endometrium, ovulation, and pregnancy. The serum levels of sex hormones including follicle-stimulating hormone(FSH), luteinizing hormone(LH), prolactin(PRL), estradiol(E_2), progestin(P), testosterone(T), free testosterone(FT), androstenedione(A2), inhibin B(INHB), and anti-Müllerian hormone(AMH) were measured. The coagulation function, traditional Chinese medicine(TCM) symptom scores, blood and urine routine, liver and kidney functions and other safety indicators were determined. Metabolomics was employed to comparatively analyze the serum metabolites of 26 patients(13 patients in each group) in the clinical study. The results showed that the total response rate and pregnancy rate of the treatment group were higher than those of the control group(P<0.001), suggesting that Bushen Culuan Formula regulated the sex hormones and ovarian function. Specifically, it reduced the levels of LH, T, FT, A2, and INHB(P<0.05 or P<0.01) and the LH/FSH ratio(P<0.05), elevated the level of P(P<0.05), promoted ovulation, increased endothelial thickness, and lowered TCM symptom scores without causing adverse reactions. A total of 24 differential metabolites were screened by metabolomics, and there were correlations between sex hormones and differential metabolites in the PCOS-induced infertility patients with kidney deficiency and blood stasis. In conclusion, Bushen Culuan Formula may regulate hormone levels through lipid and amino acid metabolism.

[Examples of Professor MA Kun's treatment of infertility caused by uterine fibroids using method of tonifying kidney and activating blood].

Uterine fibroids are a prevalent factor that impacts fertility in women of reproductive age. This study discusses the theoretical foundation and formula principles of Professor MA Kun's clinical treatment for infertility caused by uterine fibroids. The kidney stores essence and is responsible for reproduction, while blood serves as a vital material basis for women's physiological functions. Kidney deficiency is the fundamental pathogenesis of infertility, and imbalances in kidney Qi and essence or deficiencies in kidney Yin and Yang can result in blood stasis. Blood stasis plays a significant role throughout this condition by impeding the flow of blood, which is crucial for nourishing Qi. Therefore, both kidney deficiency and blood stasis are key factors contributing to infertility caused by uterine fibroids. Professor MA Kun treats infertility caused by uterine fibroids using an approach that involves tonifying the kidneys and activating blood circulation based on changes in Qi and blood during the menstrual cycle as well as follicular growth processes. By identifying stage-specific evidence, appropriate treatments can be applied accordingly. During menstruation when the uterus opens and menstrual blood flows out, promoting follicular development through nourishing kidney Yin and activating blood circulation becomes essential. In later stages of menstruation, additional measures are taken to remove blood stasis, alleviate symptoms, disperse knots, attack pathogens while simultaneously replenishing vital energy. During intermenstrual periods when Yin holds greater importance than Yang, tonifying the kidneys and activating blood circulation helps facilitate smooth discharge of eggs by promoting transformation between Yin and Yang energies. Premenstrual period to warm kidney Yang to promote pregnant egg implantation, and at the same time to dredge the liver and regulate Qi, Qi elimination stagnation, complementary in the line, with the symptoms of additional subtractions. Clinical effect is remarkable, for the reference of colleagues.

Hydrogen Source Tuned Regiodivergent Asymmetric Hydroalkylations of 2-Substituted 1,3-Dienes with Aldehydes by Cobalt-Catalysis.

Catalytic methods allowing for the reliable prediction and control of diverse regioselectivity along with the control of enantioselectivity to access different regio- and enantiomers by switching the least reaction parameters are one of the most attractive ways in organic synthesis, which provide access to diverse enantioenriched architectures from identical starting materials. Herein, a Co-catalyzed regiodivergent and enantioselective reductive hydroalkylation of 1,3-dienes with aldehydes has been achieved, furnishing different enantioenriched homoallylic alcohol architectures in good levels of enantioselectivity. The reaction features the switch of regioselectivity tuned by the selection of proton source. The use of an acid as proton source provided asymmetric 1,2-hydroalkylation products under reductive conditions, yet asymmetric 4,3-hydroalkylation products were obtained with silane as hydride source. This catalytic protocol allows for the access of homoallylic alcohols with two continuous saturated carbon centers in good levels of regio-, diastereo-, and enantioselectivity.

Achieving High-Efficient Photoelectrocatalytic Degradation of 4-Chlorophenol via Functional Reformation of Titanium-Oxo Clusters.

Rational design of crystalline catalysts with superior light absorption and charge transfer for efficient photoelectrocatalytic (PEC) reaction coupled with energy recovery remains a great challenge. In this work, we elaborately construct three stable titanium-oxo clusters (TOCs, Ti10Ac6, Ti10Fc8, and Ti12Fc2Ac4) modified with a monofunctionalized ligand (9-anthracenecarboxylic acid (Ac) or ferrocenecarboxylic acid (Fc)) and bifunctionalized ligands (Ac and Fc). They have tunable light-harvesting and charge transfer capacities and thus can serve as outstanding crystalline catalysts to achieve efficient PEC overall reaction, that is, the integration of anodic organic pollutant 4-chlorophenol (4-CP) degradation and cathodic wastewater-to-H2 conversion. These TOCs can all exhibit very high PEC activity and degradation efficiency of 4-CP. Especially, Ti12Fc2Ac4 decorated with bifunctionalized ligands exhibits better PEC degradation efficiency (over 99%) and H2 generation than Ti10Ac6 and Ti10Fc8 modified with a monofunctionalized ligand. The study of the 4-CP degradation pathway and mechanism revealed that such better PEC performance of Ti12Fc2Ac4 is probably due to its stronger interactions with the 4-CP molecule and better •OH radical production. This work not only presents the effective combination of organic pollutant degradation and simultaneously H2 evolution reaction using crystalline coordination clusters as both anodic and cathodic catalyst but also develops a new PEC application for crystalline coordination compounds.

Characteristics of white matter alterations along fibres in patients with bulimia nervosa: A combined voxelwise and tractography study.

Accumulating evidence supports the hypothesis that white matter (WM) abnormalities are involved in the pathophysiology of bulimia nervosa (BN); however, findings from in vivo neuroimaging studies have been inconsistent. We aimed to investigate the possible brain WM alterations, including WM volume and microstructure, in patients with BN. We recruited 43 BN patients and 31 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging. Differences in WM volume and microstructure were evaluated using voxel-based morphometry, tract-based spatial statistics, and automated fibre quantification analysis. Compared with HCs, BN patients showed significantly decreased fractional anisotropy in the middle part of the corpus callosum (nodes 31-32) and increased mean diffusivity in the right cranial nerve V (CN V) (nodes 27-33 and nodes 55-88) and vertical occipital fasciculus (VOF) (nodes 58-85). Moreover, we found decreased axial diffusivity in the right inferior fronto-occipital fasciculus (node 67) and increased radial diffusivity in the CN V (nodes 22-34 and nodes 52-89) and left VOF (nodes 60-66 and nodes 81-85). Meanwhile, WM microstructural changes were correlated with patients' clinical manifestations. We did not find any significant differences in WM volume and the main WM fibre bundle properties between BN patients and HCs. Taken together, these findings provide that BN shows significant brain WM reorganization, but primarily in microstructure (part of WM fibre bundle), which is not sufficient to cause changes in WM volume. The automated fibre quantification analysis could be more sensitive to detect the subtle pathological changes in a point or segment of the WM fibre bundle.

AntDAS-DDA: A New Platform for Data-Dependent Acquisition Mode-Based Untargeted Metabolomic Profiling Analysis with Advantage of Recognizing Insource Fragment Ions to Improve Compound Identification.

Data-dependent acquisition (DDA) mode in ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) can provide massive amounts of MS1 and MS/MS information of compounds in untargeted metabolomics and can thus facilitate compound identification greatly. In this work, we developed a new platform called AntDAS-DDA for the automatic processing of UHPLC-HRMS data sets acquired under the DDA mode. Several algorithms, including extracted ion chromatogram extraction, feature extraction, MS/MS spectrum construction, fragment ion identification, and MS1 spectrum construction, were developed within the platform. The performance of AntDAS-DDA was investigated comprehensively with a mixture of standard and complex plant data sets. Results suggested that features in complex sample matrices can be extracted effectively, and the constructed MS1 and MS/MS spectra can benefit in compound identification greatly. The efficiency of compound identification can be improved by about 20%. AntDAS-DDA can take full advantage of MS/MS information in multiple sample analyses and provide more MS/MS spectra than single sample analysis. A comparison with advanced data analysis tools indicated that AntDAS-DDA may be used as an alternative for routine UHPLC-HRMS-based untargeted metabolomics. AntDAS-DDA is freely available at http://www.pmdb.org.cn/antdasdda.

Translational predictions of phase 2a first-in-patient efficacy studies for antituberculosis drugs.

BACKGROUND: Phase 2a trials in tuberculosis typically use early bactericidal activity (EBA), the decline in sputum CFU over 14 days, as the primary end-point for testing the efficacy of drugs as monotherapy. However, the cost of phase 2a trials can range from USD 7 million to USD 19.6 million on average, while >30% of drugs fail to progress to phase 3. Better utilising pre-clinical data to predict and prioritise the most likely drugs to succeed will thus help to accelerate drug development and reduce costs. We aim to predict clinical EBA using pre-clinical in vivo pharmacokinetic (PK)-pharmacodynamic (PD) data and a model-based translational pharmacology approach. METHODS AND FINDINGS: First, mouse PK, PD and clinical PK models were compiled. Second, mouse PK-PD models were built to derive an exposure-response relationship. Third, translational prediction of clinical EBA studies was performed using mouse PK-PD relationships and informed by clinical PK models and species-specific protein binding. Presence or absence of clinical efficacy was accurately predicted from the mouse model. Predicted daily decreases of CFU in the first 2 days of treatment and between day 2 and day 14 were consistent with clinical observations. CONCLUSION: This platform provides an innovative solution to inform or even replace phase 2a EBA trials, to bridge the gap between mouse efficacy studies and phase 2b and phase 3 trials, and to substantially accelerate drug development.

First report of Athelia rolfsii associated with southern blight disease of Amorphophallus muelleri in China.

Amorphophallus muelleri, known as konjac, is widely used in the biomedicine and food processing due to its richness in glucomannan. Between the years of 2019 to 2022, severe outbreaks of southern blight on Am. muelleri were observed during August and September in the main planting region of Mile city. The average disease incidence was 20%, resulted in 15.3% of economic losses in approximately 10,000 m2. Infected plants showed wilting and rotting and were covered with white dense mats of mycelia and sclerotia on both petiole base and tubers. Am. muelleri petiole base covered with mycelial mats were collected for pathogen isolation. The infected tissues (n=20) were washed with sterile water and surface disinfected with 75% alcohol for 60 seconds, rinsed three times with sterile water, cultured on rose bengal agar (RBA) and incubated at 27 ℃ for two days (Adre et al. 2022). Individual hyphae were transferred to new RBA plates and incubated at 27 ℃ for 15 days to obtain purified cultures. Five representative isolates were subsequently obtained and exhibited identical morphological characteristics. All isolates produced dense, cotton-white aerial mycelia and had a daily growth rate of 1.6 ± 0.2 mm (n=5). After 10 days, all isolates formed sclerotia in spherical (diameter range 1.1 to 3.5 mm, aver. 2.0 ± 0.5 mm; n=30) and irregular shapes. The number of sclerotia per plate ranged from 58 to 113 (aver=82; n=5). These sclerotia were initially white and gradually turned brown as they matured. A representative isolate (17B-1) was selected for molecular identification and the translation elongation factor (TEF, 480 nt.), internal transcribed spacer (ITS, 629 nt.), large subunit (LSU, 922 nt.), and small subunit (SSU, 1016 nt.) regions were amplified with the primers EF595F/EF1160R (Wendland and Kothe 1997), ITS1/ITS4 (Utama et al. 2022), NS1/NS4, and LROR/LR5 (Moncalvo et al. 2000), respectively. The ITS (GenBank accession no. OP658949), LSU (OP658955), SSU (OP658952), and TEF (OP679794) sequences were 99.19%, 99.78%, 99.31%, and 99.58% similar to those of At. rolfsii isolates (MT634388, MT225781, MT103059, and MN106270, respectively). Thus, the fungus represented by isolate 17B-1 was identified as At. rolfsii, corroborating the identification of Sclerotium rolfsii Sacc., the anamorph, based on cultural and morphological features. Pathogenicity tests were performed on six-month-old asymptomatic Am. muelleri plants (n=30) grown in pots with sterile soil in a greenhouse at 27 °C and 80% relative humidity. The petiole base was scratched with a sterile blade and 20 plants were inoculated by placing a 5 mm2 mycelial plug of five-day-old isolate 17B-1 on the wound. Sterile RBA plugs were used on 10 wounded control plants. After 12 days, all inoculated plants exhibited symptoms similar to those observed in the field, while the control plants showed no symptoms. The morphological and molecular identification of the fungus reisolated from inoculated petioles confirmed its identity as At. Rolfsii, fulfilling Koch's postulates. S. rolfsii was first reported on Am. campanulatus in India (Sarma et al. 2002). As At. rolfsii causes konjac diseases in all Amorphophallus growing areas (Pravi et al. 2014), the importance of At. rolfsii as an endemic pathogen of Am. muelleri in China needs to be recognized, and its prevalence should be determined as a first step to managing this disease.

Otoprotective Effects of Fucoidan Reduce Cisplatin-Induced Ototoxicity in Mouse Cochlear UB/OC-2 Cells.

Cisplatin is a widely used standard chemotherapy for various cancers. However, cisplatin treatment is associated with severe ototoxicity. Fucoidan is a complex sulfated polysaccharide mainly derived from brown seaweeds, and it shows multiple bioactivities such as antimicrobial, anti-inflammatory, anticancer, and antioxidant activities. Despite evidence of the antioxidant effects of fucoidan, research on its otoprotective effects remains limited. Therefore, the present study investigated the otoprotective effects of fucoidan in vitro using the mouse cochlear cell line UB/OC-2 to develop new strategies to attenuate cisplatin-induced ototoxicity. We quantified the cell membrane potential and analyzed regulators and cascade proteins in the apoptotic pathway. Mouse cochlear UB/OC-2 cells were pre-treated with fucoidan before cisplatin exposure. The effects on cochlear hair cell viability, mitochondrial function, and apoptosis-related proteins were determined via flow cytometry, Western blot analysis, and fluorescence staining. Fucoidan treatment reduced cisplatin-induced intracellular reactive oxygen species production, stabilized mitochondrial membrane potential, inhibited mitochondrial dysfunction, and successfully protected hair cells from apoptosis. Furthermore, fucoidan exerted antioxidant effects against oxidative stress by regulating the Nrf2 pathway. Therefore, we suggest that fucoidan may represent a potential therapeutic agent for developing a new otoprotective strategy.

Safety and efficacy of ultrasonography of tension after zone II flexor tendon repair: A randomized controlled trial.

BACKGROUND: Primary flexor tendon repairs of lacerations in zone II of the hand are fraught with problems. Traditionally, exercise (active and passive), orthoses, and physical agents are common interventions for the rehabilitation of patients experiencing these issues. One area of focus in this field is how to safely utilize tension to lengthen gliding distance following zone II injury. Finding effective solutions in this area is a key priority for improving patient outcomes and quality of life. PURPOSE: To identify the optimal immobilization position that meets safety standards for tension and is the most efficient, and consequently, to validate our clinical effectiveness. STUDY DESIGN: A cross-sectional study was adopted for the first part of the research (Research 1). A prospective, parallel, 2-group, randomized trial was conducted with concealed allocation and single blinding in the second part of the research (Research 2). METHODS: A total of 60 healthy adults were recruited to select the best-fit protective immobilization position in Research 1, which was confirmed by tendon tension (via Young's modulus) and excursion (via gliding distance). We then randomly assigned 45 patients after zone II flexor tendon repair into two groups in Research 2 to compare functional outcomes. The control group underwent the conventional modified Duran protocol with early passive motion, while the experimental group received the protocol (optimized by Research 1) with early active motion. Ultrasonography was used to measure the tension and excursion of the flexor tendons. The outcomes measured at 16 weeks post-repair included total active motion, strength, the Disabilities of the Arm, Shoulder and Hand, and Strickland scores. RESULTS: Three participants were unable to participate in Research 2 due to medical issues and poor attendance. The investigation found that the safe tendon threshold was 345.09 ± 87.74 kPa for partial active digital motion among the 60 participants. The optimal immobilization position requires the wrist to be neutral with a flexion angle of 30° at the metacarpophalangeal joint. The grip strengths (p = 0.012), ratio of grip strength (p = 0.015), the Disabilities of the Arm, Shoulder and Hand (p = 0.036), and total active motion (p = 0.023) differed significantly between the two groups. CONCLUSIONS: Protective immobilization of the wrist in a neutral flexion position and with the metacarpophalangeal joint flexed at 30° can secure the repaired flexor tendon safely and efficiently. The effects of an early active motion protocol may improve the grip strength and upper limb mobility of individuals after zone II flexor tendon repair. CLINICAL TRIAL REGISTRATION: ChiCTR2000030592.

[Research progress on the biological effects of HIF-1α on follicle development and ovulation].

Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women's reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.

Uncovering neural pathways underlying bulimia nervosa: resting-state neural connectivity disruptions correlate with maladaptive eating behaviors.

PURPOSE: Bulimia nervosa (BN) is characterized by recurrent binge-eating episodes and inappropriate compensatory behaviors. This study investigated alterations in resting-state surface-based neural activity in BN patients and explored correlations between brain activity and eating behavior. METHODS: A total of 26 BN patients and 28 healthy controls were enrolled. Indirect measurement of cerebral cortical activity and functional connectivity (FC) analyses were performed in Surfstat. A principal component analysis (PCA) model was used to capture the commonalities within the behavioral questionnaires from the BN group. RESULTS: Compared with the healthy control group, the BN group showed decreased surface-based two-dimensional regional homogeneity in the right superior parietal lobule (SPL). Additionally, the BN group showed decreased FC between the right SPL and the bilateral lingual gyrus and increased FC between the right SPL and the left caudate nucleus and right putamen. In the FC-behavior association analysis, the second principal component (PC2) was negatively correlated with FC between the right SPL and the left caudate nucleus. The third principal component (PC3) was negatively correlated with FC between the right SPL and the left lingual gyrus and positively correlated with FC between the right SPL and the right lingual gyrus. CONCLUSION: We revealed that the right SPL undergoes reorganization with respect to specific brain regions at the whole-brain level in BN. In addition, our results suggest a correlation between brain reorganization and maladaptive eating behavior. These findings may provide useful information to better understand the neural mechanisms of BN. LEVEL OF EVIDENCE: V, descriptive study.

[Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review].

Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-ß/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.

[Evaluation methods of clinical efficacy of traditional Chinese medicine].

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.

[Problems and thoughts in clinical safety evaluation of traditional Chinese medicine].

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.