Skeletal Stem Cell-Derived Exosomes Promote Meniscal Tear Healing and Ameliorate Secondary Osteoarthritis.

BACKGROUND: The self-repair ability after meniscal tears is poor, leading to the development of posttraumatic osteoarthritis. Promoting the repair of meniscal injuries remains a great challenge, especially in the avascular region. HYPOTHESIS: Local delivery of skeletal stem cell (SSC)-derived exosomes (SSC-Exos) would promote meniscal healing and prevent secondary osteoarthritis progression. STUDY DESIGN: Controlled laboratory study. METHODS: SSCs were isolated from bone marrow and exosomes were extracted via ultracentrifugation. The cell migration capabilities after incubation with exosomes were validated through in vitro cell culture. Full-thickness longitudinal medial meniscal tears were performed in the avascular region of 40 male Sprague-Dawley rats and 20 male New Zealand White rabbits, which were randomly divided into 2 groups: group treated with phosphate-buffered saline (GCON) and group treated with exosomes (GExosome). The effects of these treatments on meniscal healing and secondary osteoarthritis were evaluated by gross inspection, biomechanical testing, and histological assessment. RNA sequencing of in vitro cell cultures was performed to explore the underlying mechanisms. RESULTS: Exosomes were successfully extracted and identified. These exosomes significantly promoted cell migration capabilities in vitro (P < .01). The GExosome exhibited greater cell proliferation and tissue regeneration with type 2 collagen secretion, and a significantly higher meniscal repair score than that of the GCON at 8 weeks postoperatively (P < .05). In contrast to the degenerative changes in both the meniscus and articular cartilage of the GCON, meniscal tissue in the GExosome exhibited restoration of normal morphology with a smooth and glossy white surface and better mechanical strength at 8 weeks after meniscal repair. Both degeneration scores and synovitis scores were significantly higher in the GCON than in the GExosome (P < .05). Compared with the GCON, the expression of key genes related to cell migration, such as the chemokine family, was enhanced by exosome injection, leading to an upregulation of extracellular matrix expression while downregulating the expression of inflammation-related genes such as CD68 and the matrix metalloproteinase family. CONCLUSION: The administration of SSC-Exos effectively promoted meniscal healing in the avascular region and ameliorated secondary osteoarthritis. The effect might be attributed to inflammation modulation, promotion of cell migration, and secretion of extracellular matrix components. CLINICAL RELEVANCE: Injection of SSC-Exos represents a promising therapeutic option for promoting meniscal healing in the avascular region.

Analysis of the uterine artery pulsatility index on the day of endometrial transformation and pregnancy outcomes of patients undergoing frozen-thawed embryo transfer.

Objective: The objective was to analyze the impact of the uterine artery pulsatility index (PI) on pregnancy outcomes by measuring uterine artery blood flow on the day of endometrial transformation in patients undergoing frozen-thawed embryo transfer (FET). Methods: This was a case-control study. In total, 2,036 patients who underwent FET at the Third Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were included. The patients were divided into a clinical pregnancy group and a nonclinical pregnancy group according to pregnancy outcome. A multivariate logistic regression model was used to analyze the factors affecting the clinical pregnancy rate. The receiver operating characteristic (ROC) curve was used to determine the optimal mean PI cutoff value of 1.75. After 1:1 propensity score matching (PSM), 562 patients were included. For statistical description and analysis, the patients were divided into two groups: a group with a mean PI > 1.75 and a group with a mean PI ≤ 1.75. Results: The clinical pregnancy group included 1,218 cycles, and the nonclinical pregnancy group included 818 cycles. There were significant differences in female age (P<0.01), infertility type (P=0.04), baseline follicle-stimulating hormone level (P=0.04), anti-Müllerian hormone (AMH) level (P<0.01), antral follicle count (P<0.01), number of transferred embryos (P=0.045) and type of transferred embryo (P<0.01). There was no significant difference in the mean bilateral PI (1.98 ± 0.34 vs. 1.95 ± 0.35, P=0.10). The multivariate analysis results showed that maternal age (AOR=0.95, 95% CI=0.93-0.98, P<0.01), AMH level (AOR=1.00, 95% CI=1.00-1.01, P=0.045), number of transferred embryos (AOR=1.98, 95% CI=1.47-2.70, P<0.01), and type of transferred embryo (AOR=3.10, 95% CI=2.27-4.23, P<0.01) were independent factors influencing the clinical pregnancy rate. The mean PI (AOR=0.85, 95% CI=0.70-1.05; P=0.13) was not an independent factor influencing the clinical pregnancy rate. Participants were divided into two groups according to the mean PI cutoff value of 1.75, and there was no significant difference between the two groups (P > 0.05). Conclusion: In this study, we found that the uterine artery PI on the day of endometrial transformation in patients undergoing FET is not a good predictor of pregnancy outcomes.

Osteogenesis or Apoptosis-Twofold Effects of Zn2+ on Bone Marrow Mesenchymal Stem Cells: An In Vitro and In Vivo Study.

Zinc (Zn) is a bioabsorbable metal that shows great potential as an implant material for orthopedic applications. Suitable concentrations of zinc ions promote osteogenesis, while excess zinc ions cause apoptosis. As a result, the conflicting impacts of Zn2+ concentration on osteogenesis could prove to be significant problems for the creation of novel materials. This study thoroughly examined the cell viability, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) cultured in various concentrations of Zn2+ in vitro and validated the osteogenesis effects of zinc implantation in vivo. The effective promotion of cell survival, proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell (BMSCs) may be achieved at a low concentration of Zn2+ (125 µM). The excessively high concentration of zinc ions (>250 µM) not only reduces BMSCs' viability and proliferation but also causes them to suffer apoptosis due to the disturbed zinc homeostasis and excessive Zn2+. Moreover, transcriptome sequencing was used to examine the underlying mechanisms of zinc-induced osteogenic differentiation with particular attention paid to the PI3K-AKT and TGF-ß pathways. The present investigation elucidated the dual impacts of Zn2+ microenvironments on the osteogenic characteristics of rBMSCs and the associated processes and might offer significant insights for refining the blueprint for zinc-based biomaterials.

Nanomedicines Promote Cartilage Regeneration in Osteoarthritis by Synergistically Enhancing Chondrogenesis of Mesenchymal Stem Cells and Regulating Inflammatory Environment.

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of the articular cartilage and inflammation. Mesenchymal stem cells' (MSCs) transplantation in OA treatment is emerging, but its clinical application is still limited by the low efficiency in oriented differentiation. In our study, to improve the therapeutic efficiencies of MSCs in OA treatment by carbonic anhydrase IX (CA9) siRNA (siCA9)-based inflammation regulation and Kartogenin (KGN)-based chondrogenic differentiation, the combination strategy of MSCs and the nanomedicine codelivering KGN and siCA9 (AHK-CaP/siCA9 NPs) was used. In vitro results demonstrated that these NPs could improve the inflammatory microenvironment through repolarization of M1 macrophages to the M2 phenotype by downregulating the expression levels of CA9 mRNA. Meanwhile, these NPs could also enhance the chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) by upregulating the pro-chondrogenic TGF-ß1, ACAN, and Col2α1 mRNA levels. Moreover, in an advanced OA mouse model, compared with BMSCs alone group, the lower synovitis score and OARSI score were found in the group of BMSCs plus AHK-CaP/siCA9 NPs, suggesting that this combination approach could effectively inhibit synovitis and promote cartilage regeneration in OA progression. Therefore, the synchronization of regulating the inflammatory microenvironment through macrophage reprogramming (CA9 gene silencing) and promoting MSCs oriented differentiation through a chondrogenic agent (KGN) may be a potential strategy to maximize the therapeutic efficiency of MSCs for OA treatment.

Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells.

Meniscus injury is one of the most common sports injuries within the knee joint, which is also a crucial pathogenic factor for osteoarthritis (OA). The current meniscus substitution products are far from able to restore meniscal biofunctions due to the inability to reconstruct the gradient heterogeneity of natural meniscus from biological and biomechanical perspectives. Here, inspired by the topology self-induced effect and native meniscus microstructure, we present an innovative tissue-engineered meniscus (TEM) with a unique gradient-sized diamond-pored microstructure (GSDP-TEM) through dual-stage temperature control 3D-printing system based on the mechanical/biocompatibility compatible high Mw poly(ε-caprolactone) (PCL). Biologically, the unique gradient microtopology allows the seeded mesenchymal stem cells with spatially heterogeneous differentiation, triggering gradient transition of the extracellular matrix (ECM) from the inside out. Biomechanically, GSDP-TEM presents excellent circumferential tensile modulus and load transmission ability similar to the natural meniscus. After implantation in rabbit knee, GSDP-TEM induces the regeneration of biomimetic heterogeneous neomeniscus and efficiently alleviates joint degeneration. This study provides an innovative strategy for functional meniscus reconstruction. Topological self-induced cell differentiation and biomechanical property also provides a simple and effective solution for other complex heterogeneous structure reconstructions in the human body and possesses high clinical translational potential.

Is there heterogeneity and moderating effect of carbon trading pilot in promoting total factor productivity?

In order to analyze what factors may affect the role of carbon trading pilot in promoting total factor productivity, this paper constructs DID model combining information of listed companies with city and industry characteristics. The moderating effect model is used to research the influence of firms' induced behavior. The results show that (1) the characteristics of a city can influence the impact of carbon trading pilot, which is associated with the city's dominant industry, resource endowment, and geographical location; (2) the effect of carbon trading pilot is heterogeneous, primarily indicating a stronger effect on high-emission industries, while having no significant impact on high-pollution industries; and (3) the induced behavior of businesses, such as increasing green innovation and environmental protection expenditure, potentially "crowding out" the effects of the carbon trading pilot.

Cumulative live birth rate in mild versus conventional stimulation in progestin-primed ovarian stimulation protocols for individuals with low prognosis.

Objective: The purpose of this study was to evaluate the cumulative live birth rate (CLBR) of mild stimulation and conventional stimulation for the low-prognosis population undergoing PPOS protocols. Methods: This was a retrospective cohort study. We included women with a low prognosis. All women underwent PPOS protocols, and the starting gonadotropin (Gn) dose was 150 IU or 300 IU. The primary outcome measure was CLBR. The secondary outcome measures were the number of oocytes retrieved, number of 2PN oocytes and number of available embryos. Results: In total, 171 women with mild stimulation and 1810 women with conventional stimulation met the criteria. In the PSM model, 171 mild stimulation cycles were matched with 513 conventional stimulation cycles. The gonadotropin dosage in the mild stimulation group was significantly lower than that in the conventional stimulation group (1878.6 ± 1065.7 vs. 2854.7 ± 821.0, P<0.001). The numbers of oocytes retrieved, 2PN oocytes, available embryos and high-quality embryos were also higher in the conventional stimulation group than in the mild stimulation group (P<0.05). There was no significant between-group difference in the cumulative clinical pregnancy rate (26.3% vs. 27.5%, P=0.77). The CLBR after mild stimulation was similar to that after conventional stimulation (21.1% vs. 22.0%, P=0.79). Conclusion: In our study, we found that the CLBRs of mild stimulation and conventional stimulation were similar, despite conventional stimulation resulting in significantly more oocytes and embryos. Thus, mild stimulation can be considered an option for women with a low prognosis in PPOS protocols.

The duration of estrogen treatment before progesterone application does not affect neonatal and perinatal outcomes in frozen embryo transfer cycles.

Objective: To explore whether the duration of estrogen treatment before progesterone application affects neonatal and perinatal outcomes in artificial frozen embryo transfer (FET) cycles. Methods: This was a retrospective cohort study. Patients who underwent FET via artificial cycles and delivered a singleton live birth between January 2015 and August 2019 were included in the analysis. According to the duration of estrogen treatment before progesterone application, we divided the cycles into four groups: ①≤12 days, ②13-15 days, ③16-19 days, and ④≥20 days. The '≤12 days group' was considered the reference group. The main outcome measures were preterm birth (PTB), small-for-gestational age (SGA), low birth weight (LBW), macrosomia, large-for-gestational age (LGA), gestational diabetes mellitus (GDM), gestational hypertension, premature rupture and placenta previa. Results: Overall, 2010 FET cycles with singleton live births were included for analysis. Cycles were allocated to four groups according to the duration of estrogen treatment before progesterone application: ①≤12 days (n=372), ②13-15 days (n=745), ③16-19 days (n=654), ④≥20 days (n=239). The neonatal outcomes, including PTB, SGA, LBW, macrosomia and LGA, were comparable among the groups (P=0.328, P=0.390, P=0.551, P=0.565, P=0.358). The rates of gestational hypertension, premature rupture and placenta previa (P=0.676, P=0.662, P=0.211) were similar among the groups. The rates of GDM among the four groups were 4.0% (15/372), 6.7% (50/745), 6.4% (42/654), and 11.3% (27/239), with statistical significance (P=0.006). After multiple logistic regression analysis, the duration of estrogen treatment did not affect the rate of GDM or other outcomes. Conclusion: The estrogen treatment duration before progesterone application does not affect neonatal and perinatal outcomes in single frozen blastocyst transfer cycles.

Comparison of the neonatal outcomes of progestin-primed ovarian stimulation and flexible GnRH antagonist protocols: a propensity score-matched cohort study.

Objective: To compare the neonatal outcomes of progestin-primed ovarian stimulation (PPOS) and flexible gonadotropin-releasing hormone (GnRH) antagonist protocols. Methods: This was a retrospective propensity score-matched (PSM) cohort study. Women who underwent their first frozen embryo transfer (FET) cycle with freezing of all embryos followed by PPOS or GnRH antagonist protocols between January 2016 and January 2022 were included. Patients using PPOS were matched with the patients using GnRH antagonist at a 1:1 ratio. The main focus of this study was the neonatal outcomes of singleton live births, including preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), macrosomia and large for gestational age (LGA). Results: After 1:1 PSM, a total of 457 PPOS and 457 GnRH antagonist protocols were included for analysis. The average starting dose of gonadotropin (275.1 ± 68.1 vs. 249.3 ± 71.3, P<0.01) and total dose of gonadotropin (2799.6 ± 579.9 vs. 2634.4 ± 729.1, P<0.01) were significantly higher in the PPOS protocol than in the GnRH antagonist protocol. The other baseline and cycle characteristics were comparable between the two protocols. The rates of PTB (P=0.14), LBW (P=0.11), SGA (P=0.31), macrosomia (P=0.11) and LGA (P=0.49) did not differ significantly between the two groups. A total of 4 patients in the PPOS group and 3 patients in the GnRH antagonist group qualified as having congenital malformations. Conclusion: PPOS resulted in singleton neonatal outcomes similar to those of a GnRH antagonist protocol. The application of the PPOS protocol is a safe option for infertility patients.

Season and temperature do not affect cumulative live birth rate and time to live birth in in vitro fertilization.

Objective: To explore whether season and temperature on oocyte retrieval day affect the cumulative live birth rate and time to live birth. Methods: This was a retrospective cohort study. A total of 14420 oocyte retrieval cycles from October 2015 to September 2019. According to the date of oocyte retrieval, the patients were divided into four groups (Spring(n=3634);Summer(n=4414); Autumn(n=3706); Winter(n=2666)). The primary outcome measures were cumulative live birth rate and time to live birth. The secondary outcome measures included the number of oocytes retrieved, number of 2PN, number of available embryos and number of high-quality embryos. Results: The number of oocytes retrieved was similar among the groups. Other outcomes, including the number of 2PN (P=0.02), number of available embryos (p=0.04), and number of high-quality embryos (p<0.01) were different among the groups. The quality of embryos in summer was relatively poor. There were no differences between the four groups in terms of cumulative live birth rate (P=0.17) or time to live birth (P=0.08). After adjusting for confounding factors by binary logistic regression, temperature (P=0.80), season (P=0.47) and duration of sunshine(P=0.46) had no effect on cumulative live births. Only maternal age (P<0.01) and basal FSH (P<0.01) had an effect on cumulative live births. Cox regression analysis suggested no effect of season(P=0.18) and temperature(P=0.89) on time to live birth. Maternal age did have an effect on time to live birth (P<0.01). Conclusion: Although season has an effect on the embryo, there was no evidence that season or temperature affect the cumulative live birth rate or time to live birth. It is not necessary to select a specific season when preparing for IVF.

Biomechanical effects of the medial meniscus horizontal tear and the resection strategy on the rabbit knee joint under resting state: finite element analysis.

The biomechanical changes following meniscal tears and surgery could lead to or accelerate the occurrence of osteoarthritis. The aim of this study was to investigate the biomechanical effects of horizontal meniscal tears and different resection strategies on a rabbit knee joint by finite element analysis and to provide reference for animal experiments and clinical research. Magnetic resonance images of a male rabbit knee joint were used to establish a finite element model with intact menisci under resting state. A medial meniscal horizontal tear was set involving 2/3 width of a meniscus. Seven models were finally established, including intact medial meniscus (IMM), horizontal tear of the medial meniscus (HTMM), superior leaf partial meniscectomy (SLPM), inferior leaf partial meniscectomy (ILPM), double-leaf partial meniscectomy (DLPM), subtotal meniscectomy (STM), and total meniscectomy (TTM). The axial load transmitted from femoral cartilage to menisci and tibial cartilage, the maximum von Mises stress and the maximum contact pressure on the menisci and cartilages, the contact area between cartilage to menisci and cartilage to cartilage, and absolute value of the meniscal displacement were analyzed and evaluated. The results showed that the HTMM had little effect on the medial tibial cartilage. After the HTMM, the axial load, maximum von Mises stress and maximum contact pressure on the medial tibial cartilage increased 1.6%, 1.2%, and 1.4%, compared with the IMM. Among different meniscectomy strategies, the axial load and the maximum von Mises stress on the medial menisci varied greatly. After the HTMM, SLPM, ILPM, DLPM, and STM, the axial load on medial menisci decreased 11.4%, 42.2%, 35.4% 48.7%, and 97.0%, respectively; the maximum von Mises stress on medial menisci increased 53.9%, 62.6%, 156.5%, and 65.5%, respectively, and the STM decreased 57.8%, compared to IMM. The radial displacement of the middle body of the medial meniscal was larger than any other part in all the models. The HTMM led to few biomechanical changes in the rabbit knee joint. The SLPM showed minimal effect on joint stress among all resection strategies. It is recommended to preserve the posterior root and the remaining peripheral edge of the meniscus during surgery for an HTMM.

Meniscus heterogeneity and 3D-printed strategies for engineering anisotropic meniscus.

The meniscus is a fibrocartilaginous tissue of the knee joint that plays an important role in load transmission, shock absorption, joint stability maintenance, and contact stress reduction. Mild meniscal injuries can be treated with simple sutures, whereas severe injuries inevitably require meniscectomy. Meniscectomy destroys the mechanical microenvironment of the knee joint, leading to cartilage degeneration and osteoarthritis. Tissue engineering techniques, as a strategy with diverse sources and customizable and adjustable mechanical and biological properties, have emerged as promising approaches for the treatment of meniscal injuries and are represented by 3D printing. Notably, the heterogeneity of the meniscus, including its anatomical structure, cell phenotype, extracellular matrix, and biomechanical properties, is crucial for its normal function. Therefore, the construction of heterogeneous tissue-engineered menisci (TEM) has become a research hotspot in this field. In this review, we systematically summarize the heterogeneity of menisci and 3D-printed strategies for tissue-engineered anisotropic menisci. The manufacturing techniques, biomaterial combinations, surface functionalization, growth factors, and bioreactors related to 3D-printed strategies are introduced and a promising direction for the future research is proposed.

Effect of Arthroscopically Confirmed Syndesmotic Widening on Outcome Following Isolated Broström Operation for Chronic Lateral Ankle Instability.

BACKGROUND: Tibiofibular syndesmosis (TFS) widening sometimes is not evident on radiography but can be found under arthroscopy in chronic lateral ankle instability (CLAI). This study aimed to evaluate the effect of TFS widening severity on clinical outcomes and return to activities after isolated Broström operation in CLAI patients and to propose an indication for its surgical intervention. METHODS: A total of 118 CLAI patients undergoing diagnostic ankle arthroscopy and open Broström-Gould operation were included. Based on the middle width of TFS measured under arthroscopy, patients were divided into the TFS-2 group (≤2 mm, n = 44), the TFS-3 group (2-4 mm, n = 42), and the TFS-4 group (≥4 mm, n = 32). The time to return to recreational sport and work, Tegner activity score, and proportion of returning to preinjury sports at the final follow-up were evaluated and compared. Other subjective evaluations included the American Orthopaedic Foot & Ankle Society score, visual analog scale, and Karlsson-Peterson score. RESULTS: Among the 3 groups, the TFS-4 group demonstrated the longest mean time to return to work and recreational sports, with the lowest proportion returning to preinjury sports. The TFS-4 group showed a significantly higher rate of sprain recurrence (12.5%) than the other 2 groups (P =.021). All the other subjective scores significantly improved after the operation without differences among the 3 groups. CONCLUSION: Concomitant severe syndesmotic widening adversely affects the return to activities after Broström operation in CLAI cases. The CLAI patients with a middle TFS width ≥4 mm were associated with delayed return to work and sports, a lower proportion of returning to preinjury sports, and more sprain recurrence, which might require further surgical intervention for syndesmosis in addition to Broström surgery. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Nanomedicines Reprogram Synovial Macrophages by Scavenging Nitric Oxide and Silencing CA9 in Progressive Osteoarthritis.

Osteoarthritis (OA) is a progressive joint disease characterized by inflammation and cartilage destruction, and its progression is closely related to imbalances in the M1/M2 synovial macrophages. A two-pronged strategy for the regulation of intracellular/extracellular nitric oxide (NO) and hydrogen protons for reprogramming M1/M2 synovial macrophages is proposed. The combination of carbonic anhydrase IX (CA9) siRNA and NO scavenger in "two-in-one" nanocarriers (NAHA-CaP/siRNA nanoparticles) is developed for progressive OA therapy by scavenging NO and inhibiting CA9 expression in synovial macrophages. In vitro experiments demonstrate that these NPs can significantly scavenge intracellular NO similar to the levels as those in the normal group and downregulate the expression levels of CA9 mRNA (≈90%), thereby repolarizing the M1 macrophages into the M2 phenotype and increasing the expression levels of pro-chondrogenic TGF-ß1 mRNA (≈1.3-fold), and inhibiting chondrocyte apoptosis. Furthermore, in vivo experiments show that the NPs have great anti-inflammation, cartilage protection and repair effects, thereby effectively alleviating OA progression in both monoiodoacetic acid-induced early and late OA mouse models and a surgical destabilization of medial meniscus-induced OA rat model. Therefore, the siCA9 and NO scavenger "two-in-one" delivery system is a potential and efficient strategy for progressive OA treatment.

Clinical outcome analysis of frozen-thawed embryo transfer on Day 7.

Objective: To investigate the clinical outcomes of Day 7 (D7) frozen-thawed embryo transfer (FET) and to provide a reference value for clinical work. Methods: This was a retrospective cohort study. Patients undergoing FET cycles in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University between December 2015 and January 2021 were included. According to the developmental stage of the embryos at transfer, the embryos were divided into three groups: Day (D) 5, D6 and D7 blastocysts. Group D7 was compared with Groups D5 and D6. Simultaneously, the preimplantation genetic testing (PGT) and non-PGT cycles in Group D7 were analyzed and compared. The main outcomes were the clinical pregnancy, live birth and miscarriage rates. The secondary outcomes were the implantation and euploidy rates. Results: In total, 5945, 4094 and 137 FET cycles were included in the D5, D6 and D7 groups, respectively. The clinical pregnancy rate was significantly lower in Group D7 than in Groups D5 (13.9% vs 62.9%, P <0.001) and D6 (13.9% vs 51.4%, P <0.001). Additionally, the live birth rate was significantly lower in Group D7 than in Groups D5 (7.3% vs 50.7%, P <0.001) and D6 (7.3% vs 40.5%, P <0.001). However, the miscarriage rate was significantly higher in Group D7 than in Groups D5 (47.4% vs 18.2%, P =0.001) and D6 (47.4% vs 20.6%, P =0.004). The clinical pregnancy and live birth rates for D7 blastocysts were significantly higher in the PGT group than in the non-PGT group (41.7% vs 13.9%, P=0.012; 33.3% vs 7.3%, P =0.003). Conclusions: D7 blastocyst transfer can yield a live birth rate that is lower than that for D5 and D6 blastocysts but has value for transfer. PGT for D7 blastocysts may reduce the number of ineffective transfers and improve the outcome of D7 blastocyst transfer, which can be performed according to a patient's situation.

Nonlinear Effects of Economic Policy Uncertainty Shocks on Carbon Emissions in China: Evidence from Province-Level Data.

Based on cross-sectional data from 30 Chinese provinces from 2004 to 2017, this paper systematically examines the nonlinear effects of economic policy uncertainty (EPU) on carbon emissions and its causes using the PSTR model. It is found that the impact of EPU on carbon emissions at the provincial level in China has significant nonlinear characteristics and shows a positive and then negative pattern as the level of EPU increases. Furthermore, increased levels of EPU also cause a nonlinear migration of the effects of provincial economic and financial development, industrial structure, government spending, and environmental regulation on carbon emissions, illustrating a large amount of heterogeneity among Chinese provinces. Specifically, provinces with higher levels of economic and financial development experience a greater positive carbon emission effect from EPU, whereas provinces with lower levels of such development experience a greater negative carbon emission effect. In contrast, in provinces with irrational industrial structures, lower fiscal expenditures, and weaker environmental controls, the nonlinear carbon emission consequences of EPU are greater. Therefore, local governments should prudently adjust economic policies, improve and perfect the market information disclosure system, and afford full play to regional comparative advantages to help achieve the "double carbon goal".

Effect of serum progesterone levels on hCG trigger day on pregnancy outcomes in GnRH antagonist cycles.

Objective: The present study analyzed the effect of hCG trigger day progesterone (P) levels on the live birth rate (LBR) in the gonadotropin-releasing hormone (GnRH) antagonist protocol. Materials and methods: This study was a single-center retrospective study. In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles performed from January 2017 to December 2020 were included in the analysis. This study included people with a normal ovarian response to fresh embryo transfer of GnRH antagonist protocols. All cycles were divided into 2 groups by P level on the day of human chorionic gonadotropin (hCG) trigger, P<1.0 ng/ml and P≥1.0 ng/ml. The primary outcome measure was LBR. Result: A total of 867 cycles with P<1.0 ng/ml and 362 cycles with P≥1.0 ng/ml were included in the analysis. The clinical pregnancy rate (CPR) was higher in the P<1.0 ng/ml group than the P≥1.0 ng/ml group (44.9% vs. 37.6%, P=0.02). The early spontaneous abortion rate was comparable between the groups (14.4% vs. 14.7%, P=0.93). For live birth, the rate for the P<1.0 ng/ml group was 35.3%, which was significantly higher than the 29.0% in the P≥1.0 ng/ml group (P=0.03). After binary logistic regression analysis, the P level on the hCG trigger day (adjusted odds ratio=0.74, 95% CI=0.55-0.99, P=0.04) was an independent risk factor for LBR. For the P level on the hCG trigger day, the LBR was lower in the P≥1.0 ng/ml group compared to the P<1.0 ng/ml group. Conclusion: For normal ovarian response patients using the GnRH antagonist protocol, serum P≥1.0 ng/ml on the hCG trigger day resulted in a lower LBR than the P<1.0 ng/ml group. When P≥1.0 ng/ml, whole embryo freezing may be considered.

The Nonlinear Influence of Environmental Regulation on the Transformation and Upgrading of Industrial Structure.

This paper measures the transformation and upgrading of industrial structure from two aspects of rationalization and upgrading of industrial structure, and empirically analyzes the impact of environmental regulation on industrial structure transformation and upgrading by using data of 29 provinces in China from 2004 to 2015. It was found that there is a significant nonlinear effect between environmental regulation and the transformation and upgrading of industrial structure. Specifically, environmental regulation is not conducive to the rational development of industrial structure, but with the continuous improvement of economic development level and human capital level, the inhibitory effect of environmental regulation on the rationalization of industrial structure is gradually weakened. The influence coefficient of environmental regulation on the rationalization of industrial structure is 0.0619~0.2648. Moreover, environmental regulation effectively drives the upgrading of industrial structure, and when the level of economic development and human capital are higher than the threshold, the role of environmental regulation in promoting the high development of industrial structure is gradually enhanced. The influence coefficient of environmental regulation on the upgrading of industrial structure is 0.0540~0.5626. Therefore, it is of great significance to formulate appropriate environmental regulation policies according to local conditions in the transformation and upgrading of industrial structure.

Anatomic reconstruction using the autologous gracilis tendon achieved less sprain recurrence than the Broström-Gould procedure but delayed recovery in chronic lateral ankle instability.

PURPOSE: To compare the return-to-activity and long-term clinical outcomes between anatomic lateral ligament reconstruction using the autologous gracilis tendon and modified Broström-Gould (MBG) procedure in chronic lateral ankle instability (CLAI). It was hypothesised that there was no difference between the two techniques. METHODS: From 2013 to 2018, 30 CLAI patients with grade III joint instability confirmed by anterior drawer test underwent anatomic reconstruction of lateral ankle ligament with the autologous gracilis tendon (reconstruction group) in our institute. Another 30 patients undergoing MBG procedure (MBG group) were matched in a 1:1 ratio based on demographic parameters. The post-operative American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) pain score, Tegner activity score, Karlsson-Peterson score, surgical complications, return-to-activities and work were retrospectively evaluated and compared between the two groups. RESULTS: All subjective scores significantly improved after the operation (all with p < 0.001) without difference between the two groups (all n.s.). The MBG group showed a significantly higher proportion of postoperative sprain recurrence than the reconstruction group (26.7% vs. 0, p = 0.002). The reconstruction group showed a significantly longer period to start walking with full weight-bearing (10.5 ± 6.9 vs. 7.0 ± 3.1 weeks, p = 0.015), jogging (17.1 ± 8.9 vs. 12.7 ± 6.9 weeks, p = 0.043) and return-to-work (13.5 ± 12.6 vs. 8.0 ± 4.7 weeks, p = 0.039) than the MBG group. CONCLUSIONS: Both anatomic reconstruction using the autologous gracilis tendon and MBG procedure could equally achieved reliable long-term clinical outcomes and the tendon reconstruction showed a relatively lower incidence of postoperative sprain recurrence but delayed recovery to walking, jogging and return-to-work. The MBG procedure was still the first choice with rapid recovery but the tendon reconstruction was recommended for patients with higher strength demand. LEVEL OF EVIDENCE: III.

Simultaneous Treatment of Osteochondral Lesion Does Not Affect the Mid- to Long-Term Outcomes of Ligament Repair for Acute Ankle Sprain: A Retrospective Comparative Study with a 3-11-Year Follow-up.

Purpose: This study aims to evaluate the mid- to long-term outcome of concurrent arthroscopic treatment of osteochondral lesion (OCL) and open anatomical repair of lateral ankle ligaments for severe acute ankle sprain patients and compare them to the outcome of those without OCL. Methods: A total of 166 patients with grade III acute lateral ankle ligament injuries underwent concurrent ankle arthroscopy and open anatomic ligament repair. Forty-three patients (group A) with OCL underwent arthroscopic treatment followed by open ligament repair. A total of 105 patients (group B) without OCL were followed up as the control. The evaluation parameters included sports recovery, postoperative visual analog scale (VAS) pain score, American Orthopaedic Foot and Ankle Society (AOFAS) score, Tegner score, sprain recurrence, satisfaction, and range of motion. Patients in group A were then subgroup-analyzed according to age, sex, body mass index, injury side, OCL location, and stage (Ferkel and Cheng's staging system). Results: The postoperative exercise level of the two groups recovered to more than 90% of the normal level (91.2% ± 11.2% in group A and 90.9% ± 13.3% in group B, n.s.). The average time of group A and group B to return to preinjury sports activity was respectively 4.4 ± 1.0 months and 4.4 ± 1.2 months with no significant difference (p = 0.716). No significant differences were found in the preoperation VAS pain score, AOFAS score, and Tegner score between the two groups. The postoperative VAS pain score in group A was significantly higher than that in group B (0.8 ± 1.7 vs. 0.3 ± 0.8, p = 0.027), but the difference was not clinically important. The postoperative VAS pain score of patients with stage D-F lesions was significantly higher than that of patients with stage B-C lesions (1.3 ± 2.1 vs. 0.3 ± 0.9, p = 0.038). Conclusions: For the severe acute ankle sprain combined with OCL, the simultaneous arthroscopic treatment and open lateral ankle ligament repair achieved good mid- to long-term outcomes. Except that the pain was more pronounced than in the control group, there were no differences in other outcomes. Postoperative pain was positively correlated with the grade of OCL.