Kidney deficiency syndrome is a common clinical syndrome in traditional Chinese medicine （TCM）. With the progress of science and technology， clinical and animal experiments on kidney deficiency syndrome have made remarkable progress. Research on kidney deficiency and the nature of "kidney" involves a large number of physiological and pathological bases， which are closely related to physiological and pathological links in the human body， among which the neuroendocrine-immune network shares the closest relationship. However， there are still many challenges in modern research on kidney deficiency syndrome， such as expert consensus on clinical diagnostic criteria and evaluation indexes and optimization of animal experimental models. In the past decade， a large number of clinical and animal experiments have been reported in the literature on kidney deficiency syndrome， among which the literature focusing on the combination of disease and syndrome is predominant， and most of them focus on kidney Yang deficiency and kidney Yin deficiency， involving the exploration of many pathological mechanisms. Research on the mechanisms related to kidney deficiency syndrome encompasses multiple signaling pathways and various biochemical indicators， including the phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-erythroid 2-relatedfactor-2（PI3K/Akt/Nrf2） signaling pathway， the Toll-like receptor 4/myeloid differentiation factor88/nuclear factor-κB（TLR4/MyD88/NF-κB） signaling pathway， the Janus kinase 2/signal transducer and activator of transcription 3（JAK2/STAT3） signaling pathway， Osteoprotectin/nuclear factor-κB receptor activator ligand/receptor activator of nuclear factor-κB （OPG/RANKL/RANK） signaling pathway. The biochemical indicators cover the cyclic adenosine monophosphate/cyclic guanosine monophosphate （cAMP/cGMP） ratio， Na⁺-K⁺-ATPase activity， Ca²⁺-Mg²⁺-ATPase activity， adrenocorticotropic hormone （ACTH）， polycorticosterone （CORT）， 17-OHCS， and other sex hormone indicators， providing crucial reference values for diagnosing kidney Yang deficiency or kidney Yin deficiency. The literature related to kidney deficiency syndrome over the past decade was collated and excavated， with a view to providing a reference for research on kidney deficiency syndrome.

OBJECTIVE To predict the in vivo bioequivalence of lenvatinib mesilate capsules and reference preparation by using the parallel artificial membrane permeability analysis. METHODS Based on the biopharmaceutics classification system classification of lenvatinib mesilate and the parallel artificial membrane permeation model, the in vitro dissolution permeation rate test model of lenvatinib mesilate capsules was established, through real-time monitoring of the dissolution and penetration of lenvartinib mesylate capsules and reference preparations in fasting gastric juice, intestinal fluid and postprandial intestinal fluid, the flux and total penetration of drugs through the membrane were calculated. RESULTS In fasting state and fed state, the 90% confidence interval of geometric mean ratio of two key quality parameters (permeation flux and permeation amount) of the preparation A all were in the range of 80.00%−125.00%, the preparation B did not fall into this interval. CONCLUSION This research method can predict the bioequivalence of renvartinib mesylate capsule and reference preparation, and has a certain correlation in vivo and in vitro.

Blood deficiency syndrome (BDS) refers to a pathological state with blood dysfunction and organ dystrophy in traditional Chinese medicine. Danggui Wuji granules (DWG) was developed from a formula containing Angelicae Sinensis Radix and Musculus et Os Galli Domestici. Herein, we investigated the mechanism of DWG in treating BDS by modulating gut microbiota. We found that DWG protected mice from BDS by elevating the levels of red blood cell count, hemoglobin, and hematocrit in peripheral blood and increasing the erythrocyte membrane Na⁺-K⁺-ATPase activity. Danggui Wuji granules changed the composition and metabolites of colonic flora. Notably, Lactobacillus, Muribaculaceae, and Alistipes were the main genera showing changes after DWG treatment. Our findings revealed that DWG presented a positive therapeutic effect on BDS in mice by regulating the gut microbiota and metabolites. The protective mechanism of DWG was associated with pathways such as metabolic pathways, biosynthesis of secondary metabolites, ABC transporters, ribosome, thyroid hormone synthesis, lysine degradation, galactose metabolism, tyrosine metabolism, etc.

In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1β, which was achieved through the suppression of the NLRP3 pathway.
Humans ; Hypoglycemic Agents/pharmacology* ; Circular Dichroism ; Cytokines ; Glucose ; Hep G2 Cells ; Insulin Resistance

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

Objective:To evaluate the effect of noninvasive prenatal testing (NIPT) as first-line screening in fetal chromosome aneuploidy screening practice, and to provide evidence for the prevention and control strategy of birth defects.Methods:Since July 2019, Hebei province had carried out the NIPT project providing first-line screening for eligible pregnant women in the area (except for those who were not applicable). Pregnant women with high risk received genetic counseling, prenatal diagnosis and intervention guidance. Low risk and false-positive ones received continuous detection and moved to prenatal diagnosis center for counseling and diagnosis if abnormities were discovered. All pregnant women were followed up to learn about pregnancy outcomes and newborn health status. Detection results and clinical data of pregnant women participating the NIPT project from July 2019 to July 2020 were collected. The detection results and effect of NIPT were analyzed.Results:(1) Basic information of the screened population: A total of 424 330 pregnant women were screened, and 423 596 were successfully detected, with a success rate of 99.83% (423 596/424 330). The age of pregnant women was (28.8±4.5) years old; the gestational age of screening was (16.6±2.3) weeks; the proportion of advanced-age pregnant women (≥35 years old) was 10.18% (43 132/423 596); in vitro fertilization-embryo transfer (IVF-ET) rate was 1.58% (6 713/423 596); the twin rate was 1.38% (5 849/423 596); the proportion of primipara was 34.23% (144 977/423 596). (2) Screening results and detection performance: totally, 325, 73 and 20 pregnant women were diagnosed with trisomy 21, 18 and 13; the sensitivity were 99.39%, 100.00% and 100.00%; the specificity were 99.98%, 99.99% and 99.98%; the positive predictive value were 75.76%, 68.87% and 21.51%, respectively. Besides, 249 190 pregnant women were received supplementary reports as well, and 255, 10 and 9 were confirmed for sex chromosome aneuploidy, other autosomal aneuploidy and deletion/duplication syndrome; the positive predictive value were 37.78%, 6.06% and 32.14%, respectively. The sensitivity of NIPT for target trisomy (trisomy 21, 18 and 13) screening in advanced-age, IVF-ET and twin pregnant women were 99.29%, 100.00% and 90.00%, respectively; the specificity were 99.93% for all; the positive predictive value were 82.25%, 61.54% and 69.23%, respectively.Conclusions:NIPT has a significant effect and good performance in the first-line screening of fetal chromosome aneuploidy in the whole population, which might provide reference for the improvement of birth defect prevention and control strategy.

Objective:To evaluate the association between polycystic ovary syndrome (PCOS)-related symptom combinations and ovarian stimulation high response in infertile patients with PCOS symptoms and controlled ovarian stimulation treatment by recombinant Human Follitropin Alfa (r-hFSHα) solution for injection, and to evaluate the efficacy and safety outcomes of using the r-hFSHα prefilled injection pen in high-risk patients with ovarian hyperstimulation syndrome (OHSS).Methods:This prospective, observational, phase Ⅳ study enrolled 1055 patients with at least one symptom/sign of PCOS using the r-hFSHα prefilled pen for over 4 months follow-up observation from December 2015 to September 2017 in the Second Hospital of Hebei Medical University, Center for Reproductive Medicine, Shandong University, Tangdu Hospital of the Air Force Military Medical University, Dalian Maternity and Child Health Care Hospital, Nanjing Maternity and Child Health Care Hospital, Jiangxi Maternity and Child Health Care Hospital, the First Affiliated Hospital of Xinjiang Medical University, the First Affiliated Hospital of Anhui Medical University, the Affiliated Hospital of Inner Mongolia Medical University. The primary endpoints assessed included the development of polycystic ovaries, elevated serum testosterone levels, menstrual cycle disturbances, development of hirsutism, and completion of egg retrieval. The efficacy endpoints of the study included the number of ocoytes retrieved, the number of M Ⅱ oocyte, the biochemical pregnancy rate, the clinical pregnancy rate, and the implantation rate. Results:In the full analysis set ( n=997), polycystic ovary rate was 54.5% (543/997), serum testosterone level was (0.4±0.2) μg/L, menstrual cycle disorder rate was 45.0% (449/997), hirsutism rate was 10.5% (105/997). The average number of oocytes retrieved after ovarian stimulation was 14.4. The clinical pregnancy rate per transfer cycle was 53.6% (251/468), the live birth rate was 45.3% (212/468), the biochemical pregnancy rate was 60.9% (285/468), the implantation rate was 39.1% (349/893), and the fresh embryo transfer cancellation rate was 24.0% (239/997). OHSS incidence was diagnosed in 1.8% (19/1054) of patients (safety set, n=1054), including 8 (0.8%) mild cases, 10 (0.9%) moderate cases and 1 (0.1%) severe case. According to the results of exploratory analysis, a decrease in body mass index (BMI) was associated with an increased risk of high response. For every 1 kg/m 2 decrease in BMI, the risk of high response (number of retrieved oocytes >15) increased by approximately 9%, the risk of high response (number of retrieved oocytes >20) increased by approximately 9%. For every 1 increase in antral follicle count (AFC), the risk of high response(number of retrieved oocytes >15) increased by approximately 6% and the risk of high response (number of retrieved oocytes >20) by approximately 4%. Conclusion:Patients with at least one symptom/sign of ovarian hyperstimulation achieved good clinical outcomes with the use of the r-hFSHα prefilled pen, and high response was associated with lower BMI and AFC.

Objective:To evaluate the association between polycystic ovary syndrome (PCOS)-related symptom combinations and ovarian stimulation high response in infertile patients with PCOS symptoms and controlled ovarian stimulation treatment by recombinant Human Follitropin Alfa (r-hFSHα) solution for injection, and to evaluate the efficacy and safety outcomes of using the r-hFSHα prefilled injection pen in high-risk patients with ovarian hyperstimulation syndrome (OHSS).Methods:This prospective, observational, phase Ⅳ study enrolled 1055 patients with at least one symptom/sign of PCOS using the r-hFSHα prefilled pen for over 4 months follow-up observation from December 2015 to September 2017 in the Second Hospital of Hebei Medical University, Center for Reproductive Medicine, Shandong University, Tangdu Hospital of the Air Force Military Medical University, Dalian Maternity and Child Health Care Hospital, Nanjing Maternity and Child Health Care Hospital, Jiangxi Maternity and Child Health Care Hospital, the First Affiliated Hospital of Xinjiang Medical University, the First Affiliated Hospital of Anhui Medical University, the Affiliated Hospital of Inner Mongolia Medical University. The primary endpoints assessed included the development of polycystic ovaries, elevated serum testosterone levels, menstrual cycle disturbances, development of hirsutism, and completion of egg retrieval. The efficacy endpoints of the study included the number of ocoytes retrieved, the number of M Ⅱ oocyte, the biochemical pregnancy rate, the clinical pregnancy rate, and the implantation rate. Results:In the full analysis set ( n=997), polycystic ovary rate was 54.5% (543/997), serum testosterone level was (0.4±0.2) μg/L, menstrual cycle disorder rate was 45.0% (449/997), hirsutism rate was 10.5% (105/997). The average number of oocytes retrieved after ovarian stimulation was 14.4. The clinical pregnancy rate per transfer cycle was 53.6% (251/468), the live birth rate was 45.3% (212/468), the biochemical pregnancy rate was 60.9% (285/468), the implantation rate was 39.1% (349/893), and the fresh embryo transfer cancellation rate was 24.0% (239/997). OHSS incidence was diagnosed in 1.8% (19/1054) of patients (safety set, n=1054), including 8 (0.8%) mild cases, 10 (0.9%) moderate cases and 1 (0.1%) severe case. According to the results of exploratory analysis, a decrease in body mass index (BMI) was associated with an increased risk of high response. For every 1 kg/m 2 decrease in BMI, the risk of high response (number of retrieved oocytes >15) increased by approximately 9%, the risk of high response (number of retrieved oocytes >20) increased by approximately 9%. For every 1 increase in antral follicle count (AFC), the risk of high response(number of retrieved oocytes >15) increased by approximately 6% and the risk of high response (number of retrieved oocytes >20) by approximately 4%. Conclusion:Patients with at least one symptom/sign of ovarian hyperstimulation achieved good clinical outcomes with the use of the r-hFSHα prefilled pen, and high response was associated with lower BMI and AFC.

Objective:To evaluate the immunogenicity of recombinant factor H binding protein(fHBP) by detecting serum antibody titer and serum bactericidal antibody test (SBA).Methods:fHBP sequence was selected and synthesized, connected to plasmid pET43.1a, transformed to Escherichia coli BL21(DE3), and expressed two recombinant fHBP proteins, included two subfamilies, fHBPA and fHBPB. After purification, the recombinant fHBP proteins were immunized to rabbits and mice. The immune antiserum titer and the bactericidal titer to epidemic strains of meningococcal bacteria group B were measured by ELISA and SBA respectively. Results:The antiserum titer of fHBP immunized rabbits was greater than 2.0×10 6, and that of immunized mice was not less than 1.0×10 6. fHBP immunized rabbit serum had bactericidal titer more than 1∶128 to 41 strains A subfamily and 20 strains B subfamily in the SBA against 69 endemic strains, and there was no cross-protection between the subfamily bacteria. The bactericidal titers of mouse serum immunized fHBPA to strains A subfamily such as Nm210902 Nm211009、Nm450522 were 1∶1 024, 1∶608、1∶861, to Nm510703、Nm311304、Nm431002 were 1∶234、1∶861、1∶430 respectively, and mouse serum immunized fHBP B to strains B subfamily Nm311302、Nm311304、Nm431002 were 1∶876、1∶274、1∶1858, all of three strains were positive in bactericidal titers. Conclusions:the titer of fHBP antiserum was higher than 1.0×10 6, the bactericidal titer was no less than 1∶128 to 61 epidemic strains, and it has a 94.2% protective effect on 69 meningococcal epidemic strains group B.

Objective:To explore the relationship between different gestational weeks of transvaginal ultrasound-guided fetal reduction and abortion in patients with multiple pregnancies after embryo transfer, and to seek the best gestational age for fetal reduction.Methods:The datas of 486 pregnant women with multiple pregnancies after embryo transfer in the Second Hospital of Hebei Medical University from January 2012 to December 2020 were retrospectively analyzed. The relationship between gestational weeks of fetal reduction and abortion rate was analyzed by curve fitting, threshold effect and multivariate logistic regression analysis.Results:After adjusting for age, infertility type, infertility years, number of births, abortion times, body mass index(BMI), various infertility and sterility factors, endometrial thickness on the day of transformation, monozygotic twins and reduction methods, when the gestational age was less than 8.43 weeks, the abortion rate increased significantly with the increase of reduction gestational age, and the abortion rate increased by 221% ( OR=3.21, 95% CI=1.47-6.99, P=0.003 3). When the gestational age of reduction ≥8.43 weeks, the abortion rate tended to be stable and did not increase ( OR=0.81, 95% CI=0.54-1.22, P=0.317 7); meanwhile, in stratified analysis, the OR value of the BMI ≥24 kg/m 2 was 12.38, and that of BMI <24kg/m 2 was 1.91, P=0.053 9. Conclusions:There is a non-linear relationship between gestational age and abortion rate of ultrasound-guided multiple pregnancy reduction in patients with embryo transfer. The abortion rate increases significantly with the increase of gestational age before 8.43 weeks of gestation. It is recommended to carry out the operation as early as possible before 8 weeks of pregnancy. The effect of BMI on the abortion rate of patients with fetal reduction needs further study.