The skeletal muscle is an important organ for movement and metabolism in human body, and its physiological aging underlies the occurrence of muscle atrophy and sarcopenia. China has the largest aging population in the world and is facing a grand challenge with how to prevent and treat skeletal muscle aging-related diseases. To address this difficult problem, the Aging Biomarker Consortium (ABC) of China has reached an expert consensus on biomarkers of skeletal muscle aging by synthesizing literatures and insights from scientists and clinicians. This consensus attempts to provide a comprehensive assessment of biomarkers associated with skeletal muscle aging, and proposes a systematic framework to classify them into three dimensions: functional, structural, and humoral. Within each dimension, the experts recommend clinically relevant biomarkers for skeletal muscle aging. This consensus aims to lay the foundation for future research on skeletal muscle aging, facilitating precise prediction, diagnosis, and treatment of skeletal muscle aging and sarcopenia. It is anticipated to make significant contributions to healthy aging of skeletal muscle in the elderly population in China and around the world as well.

BACKGROUND:Unexplained male infertility (UMI) accounts for 15%-30% of cases of male infertility, but it is poorly understood. We investigated potential risk factors for UMI leveraging data from a sperm bank with a "one male to multiple females" structure to reduce confounding arising from female factors. METHODS:Data on sperm donation provided by the Shanghai Human Sperm Bank (SHSB) to 39 qualified reproduction centres across China, along with information on IVF (In Vitro Fertilization) donor insemination cycles (DICs) performed at these centres and their reported outcomes, were retrieved from the Shanghai Human Sperm Bank (SHSB) for the period from 2004 to 2018. The association between semen parameters, demographic factors, and Cumulative Live Birth Rate from Donor Insemination (cLBR -DI) was analysed using linear regression analysis. Recurrent Failure of Sperm Donation IVF (RFDI) was defined as ≤1 pregnancy despite ≥4 DICs (indicating a cLBR -DI of ≤25%). Progressive Motility Rate (PR) refers to the percentage of grade (a + b) sperm among all sperm ((a + b)/(a + b + c + d)%). Forward Motility Rate (FR) refers to the percentage of grade (a + b) sperm among (a + b + c) sperm ((a + b)/(a + b + c)%). Sperm concentration<100 × 106/mL and FR > 95% was termed as normal group. The group with sperm concentration>200 × 106/mL or FR < 90% was termed high-risk RFDI (HR-RFDI). Logistic regression was used to assess correlations of RFDI. Propensity score matching (PSM) was used to match the RFDI and non-RFDI populations. Miscarriage conditions were also analysed in this study. FINDINGS:We included 4734 qualifying sperm donors and 17,307 IVF DICs, of which 2447 donors had more than 4 DICs per donor, forming a Pseudo-Polygyny Cohort. 8.05% of the 2447 donors with normal semen parameters and more than 4 DICs met RFDI criteria. RFDI donors exhibited higher sperm concentration (96.00 [75.00, 130.00] vs. 90.00 [72.00, 122.22], p = 0.057) and lower Forward Motility Rate (95.12 [89.02, 97.01] vs. 96.59 [93.33, 97.30], p < 0.001) compared to non-RFDI. Forward Motility Rate, rather than Progressive Motility Rate, correlated with cLBR -DI Compared to the normal group, HR-RFDI had an over three-fold higher risk of RFDI before (RR = 3.48, 95% CI [1.94, 6.25], p < 0.0001) and after (OR = 3.04, 95% CI [1.92, 4.81], p < 0.0001) PSM adjustment. Notably, RFDI donors had higher miscarriage rates (10.80 ± 14.20% vs. 3.90 ± 8.50%, p < 0.0001) compared to non-RFDI donors. High-risk RFDI donors also had higher miscarriage rates (5.40 ± 9.20% vs. 4.20 ± 9.40%, p = 0.011) compared to low-risk RFDI donors. INTERPRETATION:The negative impact of high sperm concentration on pseudo-polygyny cohort in vitro fertilization (IVF) outcomes strongly supports the hypothesis of a potential "inverted U-shape" relationship between sperm concentration and fertility. The superior correlation of FR with sperm donation IVF outcomes compared to PR suggests that FR may be a more meaningful measure of sperm motility in this context. The identification of an RFDI population, characterized by recurrent IVF failure and high miscarriage rates despite normal semen parameters, provides substantial evidence that the prevalence and severity of unexplained male infertility (UMI) may be greater than currently recognized. Therefore, a more comprehensive evaluation of male fertility should be considered in couples experiencing these issues. FUNDING:National Key R&D Program of China (2023YFC2705503), Fujian Province's Third Batch of Flexible Introduction of High-Level Medical Talent Teams (TD202307) and the National Key Technologies R&D Program (2023YFC2306700).

Manual semen evaluation methods are subjective and time-consuming. In this study, a deep learning algorithmic framework was designed to enable non-invasive multidimensional morphological analysis of live sperm in motion, improve current clinical sperm morphology testing methods, and significantly contribute to the advancement of assisted reproductive technologies. We improved the FairMOT tracking algorithm by incorporating the distance and angle of the same sperm head movement in adjacent frames, as well as the head target detection frame IOU value, into the cost function of the Hungarian matching algorithm. For sperm morphology, we used the BlendMask segmentation method to segment individual sperm. SegNet was used to separate the head, midpiece, and principal piece comments from each sperm. Experienced in vivo sperm physicians confirmed a morphological accuracy percentage of 90.82%. A total of 1272 samples were collected from multiple tertiary hospitals for validation of the system, which were also evaluated by physicians. The results of our system were highly consistent with those of manual microscopy. This study realized the automated detection of progressive motility and morphology of sperm simultaneously, which is crucial for selection of morphologically normal and motile sperm for intracytoplasmic sperm injection.

AIM:Apoptosis of vascular smooth muscle cells (VSMCs) influenced by abnormal cyclic stretch is crucial for vascular remodelling during hypertension. Lamin A/C, a nuclear envelope protein, is mechano-responsive, but the role of lamin A/C in VSMC apoptosis is still unclear.METHODS:FX-5000T Strain Unit provided cyclic stretch (CS) in vitro. AnnexinV/PI and cleaved Caspase 3 ELISA detected apoptosis. qPCR was used to investigate the expression of miR-124-3p and a luciferase reporter assay was used to evaluate the ability of miR-124-3p binding to the Lmna 3'UTR. Protein changes of lamin A/C and relevant molecules were detected using western blot. Ingenuity Pathway Analysis and Protein/DNA array detected the potential transcription factors. Renal hypertensive rats verified these changes.RESULTS:High cyclic stretch (15%-CS) induced VSMC apoptosis and repressed lamin A/C expressions compared with normal (5%-CS) control. Downregulation of lamin A/C enhanced VSMC apoptosis. In addition, 15%-CS had no significant effect on mRNA expression of Lmna, and lamin A/C degradation was not induced by autophagy. 15%-CS elevated miR-124-3p bound to the 3'UTR of Lmna and negatively regulated protein expression of lamin A/C. Similar changes occurred in renal hypertensive rats compared with sham controls. Lamin A/C repression affected activity of TP53, CREB1, MYC, STAT1/5/6 and JUN, which may in turn affect apoptosis.CONCLUSION:Our data suggested that the decreased expression of lamin A/C upon abnormal cyclic stretch and hypertension may induce VSMC apoptosis. These mechano-responsive factors play important roles in VSMC apoptosis and might be novel therapeutic targets for vascular remodelling in hypertension.

To improve development and utilization of Jinhua pig (JH) resources,we designed the crossings of Duroc × J H (D×J),Duroc × Landrace × JH (D×LJ),JH × Landrace × Yorkshire (J×LY),Duroc × JH × Landrace × Yorkshire (DJ×LY) to see how they affected the growth performance,reproductive performance,slaughter performance and meat quality,respectively,of Jinhua pigs.The results indicated that DJ×LY crossbreeding produced higher total litter size,alive litter size and newborn litter weight than the other three crossbreeding designs;D×LJ and DJ×LY had better dressing percentage and lean percentage;J×LY resulted in the highest carcass length,followed by DJ×LY cross;and DJ×LY led to the highest correct color grading and marbling scores.Taken together,all the JH crossbreeding trials in this study could serve as candidate crosses,with the DJ×LY crossbreedding being a more recommended one,for Jinhua pig production.

Chinese Meishan pig is well-known for its high prolificacy and superior meat quality.In order to detect the current situation of the conservation population,the sequencing data of 143 pigs from the four state-owned conservation farms were selected in this study.We found that all of the farms have low effective population sizes.The Middle Meishan populations have a higher proportion of polymorphic markers,and the Small Meishan populations have a higher observed heterozygosity and expected heterozygosity.It has been observed that there is an obvious genetic difference between the Middle and the Small Meishan population as the value of genetic differentiation (Fst) was 0.111 and the genetic distance (D) was 0.287.There is a weak differentiation between the two conservation farms of the Small Meishan pigs (Fst=0.055,D=0.239) but a moderate differentiation between the two conservation farms of the Middle Meishan pigs (Fst=0.127,D=0.273).This work may provide the molecular basis for the better protection and utilization of the Meishan pigs.

China has been importing enormous numbers of pigs abroad.However,whether the information offered by the exporters is reliable and whether participating in foreign breeding evaluation systems (NSR,etc.) are controversial issues.Taking one national level core breeding farm as an example which had imported pig from USA and then been a member of NSR,this study made systematic correlation analysis for four traits including "Days to 115kg","Backfat thickness","LoinMuscle Area" and "Predicted Percent Lean",and the results shown that.The breeding values offered by NSR is real,but it is not useful.For the trait of "Days to 115 kg",there seems to be a significant negative correlation between the breeding values estimated by NSR and by our method for imported ones and their progenies,which means that the results of selection based on our methods are probably opposite to the results according to NSR evaluation system.But for the other three traits,the coefficients of relationship are positively significant.However,as the selection index is composed of the sum of the weights of breeding values of "days to 115kg" and other traits,the whole index will be unreliable.Therefore,this is to say that we cannot blindly participate in the international evaluation system.When it comes to the reason of the results,it may be the interaction between genotype and environment.And further analysis is still needed to validate this hypothesis.

This study was aimed to investigate the genetic diversity and the reason for the degradation of the reproductive performance of Pudong White pig.The genetic diversity of Pudong White pig, six Taihu pig breeds and three Western pig breeds were analyzed based on the genome-wide SNPs.The genetic diversity and population structure of these pig breeds were also explored based on the SNPs related to reproductive traits.The results showed that Pudong White pig displayed a lower level of the genetic diversity than the Taihu area pig breeds.For the reproductive-related loci, except for Fengjing pig, Pudong White pig displayed the lowest propotion of polymorphic markers, expected heterozygosities and allelic richness (excluded Duroc pig).The result of PCA showed that Pudong White pig displayed its uniqueness in the reproductive-related SNPs.With the comparsion of Taihu pigs and Western populations, Pudong White pig displayed a lower level of the genetic diversity and more homozygous reproductive-related loci.Nevertheless, a certain number of favorable alleles were still harbored in Pudong White pig, which might result high heterosis in the offsprings.In conclusion, the results of this study might provide some valuable information for the breeding, conservation and utilization of this breed.

Halothane gene (Haln) is one of major genes affecting pork quality,and the recessive homozygous genotype (nn)can result in stress reaction,such as PSE and PSS.Thus,the process to remove this gene from each breed began in China since it was confirmed.However,the Haln gene still exists and the gene frequency is very high in the Pietrain population which suggested us to treat the gene dialectically.In fact,a lot of research shows heterozygous individuals (HalNn) perform better than dominant homozygous individuals (HalNN) in average daily gain,dressing percentage,lean percentage,etc.,and have no significant differences in meat quality except Water Holding Capacity.From this viewpoint,we will benefit from the following measures:(1) using Halnn males (eg.Pietrain) as terminal boars,and HalNN females (eg.Landrance×Yorkshire) as parental sows to produce HalNn commercial pigs.(2) administrating the Halnn boars more carefully and applying artificial insemination.For the reason above,it is recommended to study Haln further.

奶牛乳房炎是奶牛的常见病和多发病之一,给奶牛业带来巨大的经济损失,严重制约着奶牛业的发展.为了进一步了解乳房炎的调控机理,对已发表的5套大肠杆菌感染奶牛乳腺上皮细胞的表达谱芯片数据统一进行预处理,并整合大肠杆菌感染1、6、24 h的基因富集分析,以期得到更可靠的影响奶牛乳房炎的关键基因和通路.结果发现,感染1、6和24 h数据集的分析结果中共同下调通路分别为9、30和17个,分析结果确定了一些奶牛乳房炎相关的通路及基因,为进一步揭示其调控机理提供参考.

上海白猪（上系）（Sus scrofa）是上海市闵行区的地方培育品种,近年来,由于引进品种的冲击,其各项生产指标严重衰退,且对其种质特性、遗传基础和杂交性能等缺乏应有的了解。本研究应用全基因组范围内的遗传标记,对上海白猪（上系）群体进行了遗传多样性和群体结构的分析。首先对反映群体内遗传多样性的3个重要指标-等位基因的丰度（allelic richness,AR）、标记多态性的比例（proportion of polymorphic markers,PN）和期望杂合度（expected heterozygosity,He）进行了分析和计算。结果表明,上海白猪（上系）与太湖和西方猪种对比,其遗传多样性最高（PN=0.731,AR=1.709,He=0.221）。上海白猪（上系）与太湖品种之间的遗传分化程度（0.237±0.007）大于其与西方品种之间的遗传分化程度（0.219±0.008）。另外,用主成分分析（principal components analysis,PCA）、STRUCTURE和系统进化树等对群体结构进行了分析。结果显示,上海白猪（上系）群体内的遗传多样性比太湖猪种和西方猪种高;群体间遗传距离显示上海白猪（上系）相对于太湖猪种更接近西方猪种;主成分分析、聚类分析与群体结构分析皆显示上海白猪（上系）能够形成独立的分组。以上结果表明,从分子水平上看,将上海白猪（上系）作为一个独立的培育品种是合理的,特别是其具有独特的遗传结构,应进一步加强其保护、开发和利用。

Objective: To study and analyze the transcript and expression pattern of SOX5 in human semen, thus to provide evidence for exploring the role of transcription factor SOX5 in the process of spermatogenesis in testis. Methods: A total of 61 semen samples and 3 blood samples (as controls) collected from healthy volunteer donors at Shanghai Human Sperm Bank in September 2015 were randomly selected. Expression of SOX5 in the semen samples was detected and quantified using agarose gel electrophoresis and real time-quantitative PCR (RT-qPCR) analysis. Results: In the human semen samples, SOX5 was found in two different transcript forms: long transcript (L-SOX5) and short transcript (S-SOX5). Moreover, the S-SOX5 was specifically expressed in human semen, not detected in the control blood samples. L-SOX5 and S-SOX5 were primarily found in seminal plasma, with low expression level in sperms. The results of RT-qPCR analysis showed obviously higher mRNA expression levels of L-SOX5 than S-SOX5 in semen (0.280±0.232 vs 0.147±0.103), however, not significantly(P=0.132). Conclusion: SOX5 is expressed as different transcripts in human semen, and different transcripts may play different roles in the process of spermatogenesis in testis.

本研究旨在分析绿壳蛋鸡与白来航蛋鸡microRNA变异及其靶基因,将已鉴定的microRNA与预测microRNA组成全基因组的microRNA,并通过与GGRS得到的两种鸡群体SNP位点进行映射,挖掘含SNP的microRNA.利用生物信息学的方法,对含SNP的microRNA进行靶基因预测,并对直接含有SNP的maturemicroRNA进行聚焦.将这些靶基因进行富集,一共得到22个GO分类和10条KEGG信号通路与3个主要IPA调控网络,发现其在与生长相关的mTOR信号通路、Wnt信号通路、生长激素受体网络、胰岛素样生长因子Ⅰ受体网络得到了富集,与产蛋性状相关的卵母细胞减数分裂信号通路、黄体酮卵母细胞成熟信号通路得到了富集.此研究方法和结果可以给后期研究提供参考.

OBJECTIVE:To investigate sperm function indexes that can be used to effectively evaluate the sperm donors' fertility so as to select healthy post-thaw semen samples and improve the success rate of assisted reproductive technology. METHODS:According to the pregnancy outcomes, we divided 40 donor semen samples into a high-fertility group (n = 20) and a low-fertility group (n = 20). We measured and compared the concentration, progressive motility, morphology, acrosome intactness, DNA integrity and mitochondrial membrane potential (MMP) of the post-thaw sperm between the two groups. RESULTS:There were statistically significant differences between the high- and low-fertility groups in the percentages of morphologically normal sperm ([18.50 +/- 6.10]% vs [14.42 +/- 6.44]%, P < 0.01), acrosome intactness ([86.17 +/- 4.49]% vs [80.04 +/- 7.52]%, P < 0.05) and DNA fragmentation index ([9.21 +/- 3.22]% vs [15.72 +/- 8.20]%, P < 0.05), but not in MMP ([56.75 +/- 18.80]% vs [52.23 +/- 18.86]%, P > 0.05). A significantly positive correlation was found between MMP and sperm motility (r = 0.760, P < 0.05), but not between other sperm functions and sperm concentration and motility. CONCLUSION:Sperm concentration, motility, morphology, acrosome intactness rate and DNA integrity contribute effectively to the evaluation of the fertilization capacity of post-thaw donor semen samples.

OBJECTIVE:To investigate the effect of pre-freezing equilibration on the cryo-survival of human sperm and to optimize the protocol of direct fumigation for the freeze-thawing of human sperm.METHODS:We collected 50 semen samples from healthy donors, each subjected to cryopreservation with 3 different methods: non-equilibration freezing (Group A), 10-min equilibration at room temperature before freezing (Group B), and 10-min equilibration at 4 degrees C before freezing (Group C). We examined all the post-thaw semen samples by computer-assisted semen analysis for the sperm motility parameters, and detected the sperm vitality and deformity index (SDI).RESULTS:The recovery rate of progressive sperm motility was (61.88 +/- 16.94)% in Group C, remarkably higher than in A ([48.61 +/- 16.44]%) and B ([49.41 +/- 13.77]%) (P < 0.05), but with no significant difference between the latter two. And there were no significant differences in sperm vitality and SDI among the three groups.CONCLUSION:Ten-minute equilibration at 4 degrees C before freezing can evidently improve the progressive motility of sperm in addition to its advantages of easy operation and controllable experimental condition.

Objective To study the antihypertensive efficacy and influence on the blood pressure parameters of nifedipine GITS therapy in patients with subacute cerebral infarction with essential hypertension by ambulatory blood pressure monitoring (ABPM).Methods Fifty-one cases of subacute cerebral infarction with essential hypertension were treated with nifedipine GITS for 14 days.ABPM were performed in all cases before and after treatment.The blood pressure parameters of blood pressure variability (BPV),morning blood pressure surge(MBPS),Trough/Peak(T/P),and smoothness index(SI) were analyzed.Results (1) After treatment with nifedipine GITS 30 mg/d for two weeks,the average 24-hour systolic blood pressure (SBP),day-time systolic blood pressure (dSBP),night-time systolic blood pressure (nSBP),24-hour diastolic blood pressure (DBP),day-time diastolic blood pressure (dDBP),night-time diastolic blood pressure (nDBP) significantly decreased((144.70 ± 14.89) mm Hg vs (163.10 ± 16.48) mm Hg,(145.67 ± 15.20) mm Hg vs (164.55 ±16.81) mm Hg,(140.85 ± 19.46) mm Hg vs (156.73 ±20.55) mm Hg,(81.24 ±8.88) mm Hg vs(89.49 ± 10.06) mm Hg,(81.25 ±9.40) mm Hg vs (90.18 ± 10.64) mm Hg,(81.34 ± 12.10) mm Hg vs (86.28 ±12.11) mmHg;t=11.01,11.53,5.29,8.71,7.53,2.31;P＜0.05)).(2) Defining the standard deviation(SD) of average blood pressure as the indexes of BPV,the blood pressure variability of systolic blood pressure(SBPV),day-time systolic blood pressure variability (dSBPV),night-time systolic blood pressure (nSBPV) decreased significantly ((16.52 ± 4.38) mm Hg vs (19.78 ± 6.72) mm Hg,(15.45 ± 4.71)mm Hg vs (17.88 ± 7.25)mm Hg,(14.94 ± 5.89) mm Hg vs (19.17 ± 8.27) mm Hg; t =3.38,2.19,2.99 ;P ＜0.05)) and the diastolic blood pressure didn't change.(3) There was negative correlation between smoothness index (SI) and BPV (r =-0.28 ; P ＜ 0.05).(4) The decreases of morning blood pressure surge (MBPS) of SBP was more significant after treatment ((22.65 ± 12.77) mm Hg) than that before treatment ((31.94 ±16.36) mm Hg).(5) The median of T/P ratio calculated by group methods was 0.721 for SBP and 0.676 for DBP,and it was 0.588 ± 0.360 for SBP and 0.628 ± 0.433 for DBP calculated by individual method.The medians of T/P ratio were above 0.5 by both methods.Conclusion It is of great significance to effectively control blood pressure and BPV in patients with stroke.Nifedipine GITS can constantly release medicine;it can lower the blood pressure,and significantly reduce BPV and MBPS.

目的:拟通过比较梗阻(OA)和非梗阻性无精子(NOA)症患者精液细胞DNA倍体分析与细胞学检查结果的特点,以期建立一种无创的诊疗方案以鉴别OA与NOA.方法:NOA患者20例和OA患者10例,按照WHO方法进行精液分析诊断,获取其精液标本,液化后离心取沉淀物,1份采用体积分数70％冰乙醇重悬精液沉淀,4℃固定后用PI染色,采用流式细胞仪进行DNA倍体分析.同时,取另1份精液沉淀涂片,进行Diff-Quick染色和免疫细胞化学染色.结果:DNA倍体分析结果表明,20例NOA患者精液中均存在单倍体(1N)、二倍体(2N)和四倍体(4N)细胞,其中2N细胞含量最高,约占71.25±8.73％.1N细胞的百分比含量为5.46±2.93％,4N细胞含量为3.28±2.54％.10例OA患者精液中有8例只存在2N细胞,含量为71.67±13.09％,未检测到1N和4N,2例未检测到各种倍体细胞.精液细胞学检查结果表明,20例NOA患者中有15例患者精液中可检测出生精细胞,5例患者精液中未检出生精细胞.10例OA患者精液中均未检出生精细胞,其中2例没有任何细胞.结论:精液细胞DNA倍体分析与细胞学检查作为2种无创的检查方法,均可作为评估患者生精功能的辅助诊疗手段,两者结合可作为鉴别OA和NOA的辅助诊断指标.

Objective To investigate the expression of GRP78 and caspase4,which are both endoplasmic reticulum stress associated molecules,in the resceted temporal cortex from patients with refractory temporal lobe epilepsy and explore the role of endoplasmic reticulum stress in the brain injury of human temporal lobe epilepsy.Methods The specimens were obtained from 32 patients with refractory temporal lobe epilepsy.Immunohistochemistry and western blot were used to determine the expression levels of GRP78 and caspase4,and compared to the controls with sex and age matched.Results GRP78 and caspase4 were obviously upregulated in the epilepsy brain if compared with the controls(P0.05).Conclusion Chronic epilepsy induces endoplasmic reticulum stress and caspase4 may invlove in injury brain after repeated seizures,which may provide a new therapeutic target to prevent brain damage caused by eplilepsy.

抑郁是癫痫患者中常见的精神障碍,严重地影响了患者的生活质量.传统的观点认为癫痫患者因为存在着诸多社会学问题易出现抑郁倾向,癫痫和抑郁是单向的联系,但大量的研究已经证明癫痫和抑郁之间存在双向的联系,一种异常状态的存在可能易转化为另一种异常状态的发展.癫痫和抑郁存在着共同的发病机制.本文主要就癫痫和抑郁的双向联系以及抗抑郁药物在癫痫患者中的应用进行阐述.

Type 1 diabetes can be distinguished to two types according to the pathogenesy: autoimmunity(type 1A) and idiopathic(type 1b).In type 1A,there are many insular autoantibodies,such as Islet cell cytoplasmic autoantibodies(ICA),anti-insulin antibodies(IAA),glutamic acid decarboxylase antibodies(GADA) and protein tyrosine phosphatase antibodies(IA-2A).In type 1B,the etiopathogenisis is not clear yet,but many species of insular autoantibodies can be discovered in these patients,including the antibodies to carboxypeptide-H(CPHAb) and SOX13(ICA12).The antibodies should be used not only on the diagnosis and screen of idopathic type 1 diabetes but also the etiopathogenisis and prevention and cure of the disease.