Objective:To investigate the pregnancy outcomes and cumulative live birth rate (CLBR) after in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in patients with high basal follicle-stimulating hormone (bFSH) levels. Methods:This retrospective cohort study included clinical data from patients who underwent IVF/ICSI-ET treatment at the Reproductive Medical Center of Peking University Third Hospital from January 2018 to December 2022. Patients were divided into three groups based on the highest bFSH level during all cycles of treatment: group A (15 U/L≤bFSH<25 U/L), group B (25 U/L≤bFSH<40 U/L), and group C (bFSH≥40 U/L). After propensity score matching (PSM) based on the female body mass index, the baseline data, embryology laboratory outcomes, and assisted reproductive outcomes such as clinical pregnancy rate among the three groups of patients were compared. Binary logistic regression analysis was used to explore the impact of various factors on live birth, and the trend of CLBR across multiple cycles was also studied.Results:After PSM, 340 cycles were included in group A, 340 cycles were included in group B, 127 cycles were included in group C. There were statistically significant differences among the three groups in antral follicle count, bFSH, basal progesterone, basal luteinizing hormone, and anti-Müllerian hormone levels ( P=0.004, P<0.001, P<0.001, P<0.001, P<0.001). In the analysis of controlled ovarian stimulation (COS) protocols, groups A and B mainly used conventional COS protocol, while group C primarily used mild stimulation protocol. The duration and dosage of gonadotropin used were the highest in group A [10 (7, 12) d, 2 728 (1 650, 3 725) U], with statistically significant differences among the three groups (all P<0.001). On the day of human chorionic gonadotropin injection, there were statistically significant differences in estradiol and progesterone levels among the three groups ( P=0.022 and P=0.048, respectively). The cancellation rate of cycles did not differ significantly among the three groups ( P>0.05), while the number of oocytes retrieved ( P<0.001) and the rate of cycles with no transferable embryos ( P=0.034) showed statistically significant differences. The type of embryos transferred in all three groups was mainly cleavage-stage embryos, and there were statistically significant differences in the rate of two pronuclei and high-quality embryos among the groups ( P=0.003 and P=0.006, respectively). The rate of high-quality embryos decreased with increasing bFSH levels, and comparisons between group A and group B, as well as group A and group C, showed statistically significant differences (all P<0.016 7). The biochemical pregnancy rate and the clinical pregnancy rate in fresh cycles differed significantly among the three groups ( P=0.025 and P=0.010, respectively), while the live birth rate per initiated cycle showed marginal significance ( P=0.058). However, the miscarriage rate and the live birth rate per transfer cycle did not differ significantly among the groups (all P>0.05). Binary logistic regression analysis revealed that bFSH ( OR=0.955, 95% CI: 0.912-1.000, P=0.050) and the number of oocytes retrieved ( OR=1.104, 95% CI: 1.009-1.207, P=0.031) were independent predictors of live birth. Analysis of CLBR curves across multiple oocyte retrieval cycles showed that CLBR gradually increased with the number of oocyte retrievals and stabilized at 14.32% after the fifth retrieval. Conclusion:High bFSH levels reduce the live birth rate per initiated cycle but do not affect the live birth rate per transfer cycle. Increasing age and a low number of oocytes retrieved can both decrease the live birth rate. Multiple oocyte retrieval and transfer cycles can improve CLBR in patients with high bFSH level to some extent, but it tends to stabilize after the fifth cycle.

Objective:To investigate the pregnancy outcomes and cumulative live birth rate (CLBR) after in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in patients with high basal follicle-stimulating hormone (bFSH) levels. Methods:This retrospective cohort study included clinical data from patients who underwent IVF/ICSI-ET treatment at the Reproductive Medical Center of Peking University Third Hospital from January 2018 to December 2022. Patients were divided into three groups based on the highest bFSH level during all cycles of treatment: group A (15 U/L≤bFSH<25 U/L), group B (25 U/L≤bFSH<40 U/L), and group C (bFSH≥40 U/L). After propensity score matching (PSM) based on the female body mass index, the baseline data, embryology laboratory outcomes, and assisted reproductive outcomes such as clinical pregnancy rate among the three groups of patients were compared. Binary logistic regression analysis was used to explore the impact of various factors on live birth, and the trend of CLBR across multiple cycles was also studied.Results:After PSM, 340 cycles were included in group A, 340 cycles were included in group B, 127 cycles were included in group C. There were statistically significant differences among the three groups in antral follicle count, bFSH, basal progesterone, basal luteinizing hormone, and anti-Müllerian hormone levels ( P=0.004, P<0.001, P<0.001, P<0.001, P<0.001). In the analysis of controlled ovarian stimulation (COS) protocols, groups A and B mainly used conventional COS protocol, while group C primarily used mild stimulation protocol. The duration and dosage of gonadotropin used were the highest in group A [10 (7, 12) d, 2 728 (1 650, 3 725) U], with statistically significant differences among the three groups (all P<0.001). On the day of human chorionic gonadotropin injection, there were statistically significant differences in estradiol and progesterone levels among the three groups ( P=0.022 and P=0.048, respectively). The cancellation rate of cycles did not differ significantly among the three groups ( P>0.05), while the number of oocytes retrieved ( P<0.001) and the rate of cycles with no transferable embryos ( P=0.034) showed statistically significant differences. The type of embryos transferred in all three groups was mainly cleavage-stage embryos, and there were statistically significant differences in the rate of two pronuclei and high-quality embryos among the groups ( P=0.003 and P=0.006, respectively). The rate of high-quality embryos decreased with increasing bFSH levels, and comparisons between group A and group B, as well as group A and group C, showed statistically significant differences (all P<0.016 7). The biochemical pregnancy rate and the clinical pregnancy rate in fresh cycles differed significantly among the three groups ( P=0.025 and P=0.010, respectively), while the live birth rate per initiated cycle showed marginal significance ( P=0.058). However, the miscarriage rate and the live birth rate per transfer cycle did not differ significantly among the groups (all P>0.05). Binary logistic regression analysis revealed that bFSH ( OR=0.955, 95% CI: 0.912-1.000, P=0.050) and the number of oocytes retrieved ( OR=1.104, 95% CI: 1.009-1.207, P=0.031) were independent predictors of live birth. Analysis of CLBR curves across multiple oocyte retrieval cycles showed that CLBR gradually increased with the number of oocyte retrievals and stabilized at 14.32% after the fifth retrieval. Conclusion:High bFSH levels reduce the live birth rate per initiated cycle but do not affect the live birth rate per transfer cycle. Increasing age and a low number of oocytes retrieved can both decrease the live birth rate. Multiple oocyte retrieval and transfer cycles can improve CLBR in patients with high bFSH level to some extent, but it tends to stabilize after the fifth cycle.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

The methodological framework for interventional clinical research of Chinese medicine （CM） under the research mode of syndrome dominating disease provides a set of technical principles and methods to design， evaluate， and implement of this kind. It consists of three main parts including general principles， research points and key design elements， with a total of 25 items. This methodological framework proposes implementing requirements and recommendations in a variety of aspects， including basic norms to be followed in relevant studies， perspectives for selecting research topics， as well as the technological details on study population （P）， intervention （I） and comparison（C）， outcome measurement （O）， time frame （T） of treatment and follow-up， sample orientation （prospective versus retrospective）， study design （S） format and type. To provide practical guidance for future studies， this article clearly explains each items of the methodological framework through some supportive cases.

BACKGROUND:There is a very close relationship between osteoporosis and periodontal disease in postmenopausal women, but the mechanism remains unclear. OBJECTIVE:To investigate the expression of nuclear factor-κB in the alveolar bone andinterleukin-17 in the serum and gingiva in the mouse model of osteoporosis caused by ovariectomy. METHODS:Female mice aged 3 months were randomly divided into ovariectomy and sham operation groups. At 6 months after surgery, the mouse models were evaluated histologically on the submandibular bone and thigh bone stained with hematoxylin and eosin. In the submandibular bone, the expression levels of OCN and Runx2 were detected by RT-PCR, and the expression level of nuclear factor-κB was detected by immunohistochemical staining and western blot assay. Besides, the expression level of interleukin-17 in the serum and gingival homogenate was evaluated using Cytometric Beads Array. RESULTS AND CONCLUSION:The thigh bone in the ovariectomy group revealed the thin cortical bone, enlarged marrow cavity, and increased resorption lacunae, as well as fewer, thinner trabeculae with lower density and irregular structure. Compared with the sham operation group, the expression levels of OCN and Runx2 in the alveolar bone were decreased in the ovariectomy group. The activation of nuclear factor-κB (P65)appeared with P65 positive expression in the submandibular bone in the ovariectomy group, and the relative expression level was higher than that in the sham operation group. The serum level of interleukin-17 in the ovariectomy group was higher than that in the sham operation group, but the level in the gingival tissue showed no significant difference between the two groups. These results indicate that estrogen deficiency after ovariectomy can activate nuclear factor-κB signal pathway to play a role in periodontal osteolysis. However interleukin-17 in the local periodontal tissue may not be a key cytokine to damage the periodontal tissue.

T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy.However,many challenges remain in extending its application toward the treatment of solid tumors.The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy.One negative regulator of T cell activity is lymphocyte activation gene-3 (LAG-3).We successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture.LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model,which is comparable to standard CAR-T cells.Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.

Objective To introduce a community-based rehabilitation(CBR) network model in Shijiazhuang,Hebei province.Methods The work model in Qiaodong district in Shijiazhuang city was evaluated according to the national CBR standard and analyzed.Results Their work has met the national standard,the score of management section was the highest among all areas.Conclusion The work was featured by government dominate,strong management network and technical support.It implied the social model of CBR.

Objective:To assess the effects of different fluid therapies on myocardial function,blood-spinal cord barrier and water content of spinal cord after acute high level spinal cord injury(SCI) in rats.Methods: Thirty-two male SD rats, weighing (300?20) g, were anesthetized intraperitoneally with pentobarbital (40 mg/kg). A cervical laminectomy extending from C6-T1 was performed and the experimental acute cervical 7 spinal cord injury model was created by modified Allen’s method,and then the rats were randomly divided into 4 groups(n=8): control group(C group) with no fluid resuscitation, 7.5% hypertonic saline group(HS group), 6% hydroxyethyl starch group(HES group) and banlanced solution group (BS group).Fifteen minutes after injury, rats of each treatment groups were given (iv. at 4 ml/kg) above-mentioned fluids in 4 min,then continuously infused at a rate of 10 ml?kg -1 ?h -1 over for 30 min.MAP,HR,left ventricular systolic pressure (LVSP),and ?dp/dt max were recorded at 5,15 and 30 min.At 30 min, 0.5% Evan's blue(EB) 1 ml was injected iv.Two hours later the animals were sacrificed and the injured segments of spinal cords were removed for determination of water content and EB content.Results:After SCI there were no differences of HR at different time points in each group. At 5 min,HS significantly increased MAP,LVSP and ?dp/dt max compared with control group(P

Objective:To observe the changes of ? 1 -adrenergic receptors expression in a high-level spinal cord injury (SCI) rat model,providing information for studying the mechanisms of severe hypertension of autonomic dysreflexia.Methods: Adult male Wistar rats were divided into 2 groups: sham-lesion group(n=6) and SCI group(n=36). Severe spinal crush injury was induced at T 4 using modified Allens device in SCI group, while sham-lesion group received laminectomy at T 4 only.The expression of ? 1 -adrenergic receptors mRNA in different segments of spinal cord:injured segment(I), above(A) and below(B) the injured site, were measured by reverse-transcription polymerase chain reaction (RT-PCR) 1 d, 3 d, 7 d, 2 weeks, 3 weeks and 4 weeks after SCI. Results: Compared with sham-lesion group,the express of ? 1 -adrenergic receptors mRNA in group A decreased 3 d after SCI and dropped to the least 1 week later,and restored to the normal level 2 weeks later.The impairment of ? 1 -adrenergic receptors mRNA expression in group I occured immediately after SCI and hit the lowest value 3 d later,and did not recover to the nomal 4 weeks later.Decrease of ? 1 -adrenergic receptors mRNA expression in group B were detected 1 d after SCI,but began to increase on 3 d and exceeded that of group C 4 weeks later.Conclusion: In chronic SCI rat models ? 1 -adrenergic receptors expression increases below the level of SCI,which might be a contributing factor to the severe hypertension of autonomic dysreflexia.