Prenatal prednisone exposure disturbs fetal kidney development and its characteristics.

Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication. Now, it is also recognized as an emerging environmental contaminant. Pregnant women may be exposed to prednisone actively or passively through multiple pathways and cause developmental toxicity to the fetus. However, the impact of prenatal prednisone exposure (PPE) on fetal kidney development remains unclear. In this study, pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses (0.25, 0.5, or 1 mg/(kg·day)), or at the dose of 1 mg/(kg·day) in different gestational days (GD) (GD0-9, GD10-18, or GD0-18). The pregnant mice were euthanized on GD18. HE staining revealed fetal kidney dysplasia, with an enlarged glomerular Bowman's capsule space and a reduced capillary network in the PPE groups. The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups. However, overall gene expression in renal tubules and collecting ducts were markedly increased. All of the above effects were more pronounced in high-dose, full-term pregnancy, and female fetuses. Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2, increased the expression of Hnf1ß, Hnf4α, and Wnt9b, and inhibited the expression of glial cell line-derived neurotrophic factor (GDNF) and Notch signaling pathways. In conclusion, this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney, and the time effect is manifested as full-term pregnancy > early pregnancy > mid-late pregnancy.

Targeting CK2 eliminates senescent cells and prolongs lifespan in Zmpste24-deficient mice.

Senescent cell clearance is emerging as a promising strategy for treating age-related diseases. Senolytics are small molecules that promote the clearance of senescent cells; however, senolytics are uncommon and their underlying mechanisms remain largely unknown. Here, we investigated whether genomic instability is a potential target for senolytic. We screened small-molecule kinase inhibitors involved in the DNA damage response (DDR) in Zmpste24-/- mouse embryonic fibroblasts, a progeroid model characterized with impaired DDR and DNA repair. 4,5,6,7-tetrabromo-2-azabenzamidazole (TBB), which specifically inhibits casein kinase 2 (CK2), was selected and discovered to preferentially trigger apoptosis in Zmpste24-/- cells. Mechanistically, inhibition of CK2 abolished the phosphorylation of heterochromatin protein 1α (HP1α), which retarded the dynamic HP1α dissociation from repressive histone mark H3K9me3 and its relocalization with γH2AX to DNA damage sites, suggesting that disrupting heterochromatin remodeling in the initiation of DDR accelerates apoptosis in senescent cells. Furthermore, feeding Zmpste24-deficient mice with TBB alleviated progeroid features and extended their lifespan. Our study identified TBB as a new class senolytic compound that can reduce age-related symptoms and prolong lifespan in progeroid mice.

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus.

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

Development of a green, concise synthesis of nicotinamide derivatives catalysed by Novozym® 435 from Candida antarctica in sustainable continuous-flow microreactors.

An increasing number of studies have shown that many nicotinamide derivatives exhibited extensive biological activities, such as anti-inflammatory and antitumor activity. In this paper, a green, concise synthesis of nicotinamide derivatives in sustainable continuous-flow microreactors catalysed by Novozym® 435 from Candida antarctica has been developed. Application of an easily obtainable and reusable lipase in the synthesis of nicotinamide derivatives from methyl nicotinate and amines/benzylamines reacted for 35 min at 50 °C led to high product yields (81.6-88.5%). Environmentally friendly tert-amyl alcohol was applied as a reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further activity research of novel nicotinamide derivatives.

Azithromycin exposure during pregnancy disturbs the fetal development and its characteristic of multi-organ toxicity.

AIMS: Azithromycin is widely used in clinical practice for treating maternal infections during pregnancy. Meanwhile, azithromycin, as an "emerging pollutant", is increasingly polluting the environment due to the rapidly increasing usage (especially after the COVID-19). Previous studies have suggested a possible teratogenic risk of prenatal azithromycin exposure (PAzE), but its effects on fetal multi-organ development are still unclear. This study aimed to explore the potential impacts of PAzE. MATERIALS AND METHODS: We focused on pregnancy outcomes, maternal/fetal serum phenotypes, and fetal multiple organ development in mice at different doses (50/200 mg/kg·d) during late pregnancy or at 200 mg/kg·d during different stages (mid-/late-pregnancy) and courses (single-/multi-course). KEY FINDINGS: The results showed PAzE increased the rate of the absorbed fetus during mid-pregnancy and increased the intrauterine growth retardation rate (IUGR) during late pregnancy. PAzE caused multiple blood phenotypic changes in maternal and fetal mice, among which the number and degree of changes in fetal blood indicators were more significant. Moreover, PAzE inhibited long bone/cartilage development and adrenal steroid synthesis, promoting hepatic lipid production and ovarian steroid synthesis in varying degrees. The order of severity might be bone/cartilage > liver > gonads > other organs. PAzE-induced multi-organ alterations differed in stages, courses doses and fetal sex. The most apparent changes might be in high-dose, mid-pregnancy, multi-course, and female, while there was no typical rule for a dose-response relationship. SIGNIFICANCE: This study confirmed PAzE could cause fetal developmental abnormalities and multi-organ functional alterations, which deepens the comprehensive understanding of azithromycin's fetal developmental toxicity.

Prenatal exposure to corn oil, CMC-Na or DMSO affects physical development and multi-organ functions in fetal mice.

Corn oil, sodium carboxymethyl cellulose (CMC-Na), and dimethyl sulfoxide (DMSO) are widely used as solvents or suspensions in animal experiments, but the effects of prenatal exposure to them on fetal development have not been reported. In this study, Kunming mice were given a conventional dose of corn oil (9.2 g/kg·d), CMC-Na (0.05 g/kg·d) or DMSO (0.088 g/kg·d) during gestation days 10-18, and the pregnancy outcome, fetal physical development, serum phenotype, and multi-organ function changes were observed. The results showed that corn oil decreased serum triglyceride level in males but increased their serum testosterone and CORT levels, and affected female placenta and female/male multi-organ functions (mainly bone, liver, kidney). CMC-Na increased female/male body lengths and tail lengths, decreased serum glucose and total cholesterol levels in males as well as increased their serum LDL-C/HDL-C ratio and testosterone level, decreased female serum bile acid level, and affected male/female placenta and multi-organ functions (mainly bone, liver, hippocampus). DMSO decreased male body weight and serum glucose level, decreased male/female serum bile acid levels, and affected male/female placenta and multi-organs functions (mainly bone, hippocampus, adrenal gland). In conclusion, prenatal exposure to a conventional dose of corn oil, CMC-Na or DMSO could affect fetal physical development and multi-organ functions, and has the characteristics of "multi-pathway, multi-organ and multi-target". This study provides the experimental basis for the rational selection of solvents or suspensions in pharmacology and toxicology studies.

Role of C-Terminal Phosphorylation of Lamin A in DNA Damage and Cellular Senescence.

The nuclear matrix protein lamin A is a multifunctional protein with roles in DNA replication and repair, gene activation, transcriptional regulation, and maintenance of higher-order chromatin structure. Phosphorylation is the main determinant of lamin A mobility in the nucleus and nuclear membrane dissolution during mitosis. However, little is known about the regulation of lamin A phosphorylation during interphase. Interestingly, C-terminal lamin A mutations trigger cellular senescence. Recently, we showed that the C-terminal region of lamin A interacts with casein kinase II (CK2). In the present study, we have expanded on our previous research to further investigate lamin A phosphorylation and elucidate the mechanisms underlying the effect of C-terminal mutations on cellular senescence. Our results indicate that glycogen synthase kinase 3ß (GSK3ß) and CK2 jointly mediate the phosphorylation of lamin A at C-terminal Ser628 and Ser636 residues. Furthermore, a loss of phosphorylation at either of these two sites affects the nuclear distribution of lamin A, leading to an impaired DNA damage response as well as cellular senescence. Thus, phosphorylation at C-terminal sites in lamin A appears to be important for maintaining genomic stability and preventing cellular senescence. These findings provide insight into how loss of the C-terminal region of lamin A may induce premature aging. Furthermore, enhancement of GSK3ß and CK2 activity may represent a possible therapeutic approach for the treatment of aging-related diseases.

Balance training benefits chronic ankle instability with generalized joint hypermobility: a prospective cohort study.

BACKGROUND: Balance training is the first choice of treatment for chronic ankle instability (CAI). However, there is a lack of research on the effects of balance training in CAI with generalized joint hypermobility (GJH). This study is to compare the outcomes of balance training in CAI patients with and without GJH. METHODS: Forty CAI patients were assigned into the GJH group (Beighton ≥ 4, 20) and non-GJH group (Beighton < 4, 20) and they received same 3-month supervised balance training. Repeated measure ANOVA and independent t test were used to analyze self-reported questionnaires (Foot and ankle ability measure, FAAM), the number of patients experiencing ankle sprain, isokinetic muscle strength and postural control tests (Star excursion balance test, SEBT and Balance errors system, BES) before training, post-training immediately, and post-training 3 months, respectively. RESULTS: At baseline, no differences were found between groups with except for GJH group having poorer SEBT in the posteromedial direction (83.6 ± 10.1 vs 92.8 ± 12.3, %) and in the posterolateral direction (84.7 ± 11.7 vs 95.7 ± 8.7, %). Following the balance training, GJH group demonstrated lower re-sprain ratio (immediately after training, 11.1% vs 23.5%, 3 month after training, 16.7% vs 29.4%) than non-GJH group, as well as greater FAAM-S score, plantarflexion strength and dorsiflexion strength at post-training immediately and 3 months, and both groups improved similarly in the FAAM-A score, muscle strength and balance control (SEBT in the posterior-lateral and posterior-medial directions, and BES scores) compared with baseline. CONCLUSIONS: CAI patients with GJH gained equally even better postural stability and muscle strength after the balance training than the non-GJH patients. Balance training could still be an effective treatment for CAI patients with GJH before considering surgery. TRIAL REGISTRATION: ChiCTR1900023999, June 21st, 2019.

Low H3K27 acetylation of SF1 in PBMC: a biomarker for prenatal dexamethasone exposure-caused adrenal insufficiency of steroid synthesis in male offspring.

Dexamethasone is widely used to treat pregnancy disorders related to premature delivery. However, lots of researches have confirmed that prenatal dexamethasone exposure (PDE) could increase the risk of offspring multiple diseases. This study was designed to elucidate the epigenetic mechanism of adrenal developmental programming and explore its early warning marker in peripheral blood mononuclear cells (PBMC). We found the adrenal morphological and functional changes of PDE male offspring rats before and after birth, which were mainly performed as the decreased serum corticosterone concentration, steroidogenic acute regulatory (StAR) protein expression, and histone 3 lysine 27 acetylation (H3K27ac) level of steroidogenic factor 1 (SF1) promoter region and its expression. Simultaneously, the expressions of glucocorticoid receptor (GR) and histone acetylation enzyme 5 (HDAC5) in the PDE male fetal rats were increased. In vitro, dexamethasone reduced the expression of SF1, StAR, and cortisol production and still increased the expression of GR and HDAC5, the binding between GR and SF1 promoter region, and protein interaction between GR and HDAC5. GR siRNA or HDAC5 siRNA was able to reverse the above roles of dexamethasone. Furthermore, in vivo, we confirmed that H3K27ac levels of SF1 promoter region and its expression in PBMC of the PDE group were decreased before and after birth, showing a positive correlation with the same indexes in adrenal. Meanwhile, in clinical trials, we confirmed that prenatal dexamethasone application decreased H3K27ac of SF1 promoter region and its expression in neonatal PBMC. In conclusion, PDE-caused adrenal insufficiency of male offspring rats was related to adrenal GR activated by dexamethasone in uterus. The activated GR, on the one hand, increased its direct binding to SF1 promoter region to inhibit its expression, on the other hand, upregulated and recruited HDAC5 to decrease H3K27ac level of SF1 promoter region, and strengthened the inhibition of SF1 and subsequent StAR expression.

Arthroscopic Anatomical Double-Bundle Medial Patellofemoral Complex Reconstruction Improves Clinical Outcomes in Treating Recurrent Patellar Dislocation Despite Trochlear Dysplasia, Elevated Tibial Tubercle-Trochlear Groove Distance, and Patellar Alta.

PURPOSE: To evaluate the clinical outcomes of arthroscopically assisted double-bundle medial patellofemoral complex reconstruction (MPFC-R). METHODS: A retrospective review was carried out among adult patients who experienced at least 2 patellar dislocations and underwent primary arthroscopically assisted MPFC-R between January 2014 and November 2019. Dejour classification, tibial tubercle-trochlear groove (TT-TG) distance, and patellar height (with Insall-Salvati index) were measured. Pre- and postoperative patellar tilt were compared. Information on outcome scores, ability to return to sports, postoperative recurrent dislocations, and complications was recorded. RESULTS: A total of 42 MPFC-Rs in 39 patients were included. Mean age at surgery was 22.2 ± 7.6 years; 69.2% of patients were female. Mean follow-up was 47.3 ± 20.2 months. Seventy-four percent of cases had Dejour B (19.0%), C (33.3%), and D (21.4%) trochlear dysplasia; mean TT-TG distance was 19.6 ± 3.5 mm, and mean Insall-Salvati index was 1.21 ± 0.17. Mean patellar tilt decreased from 27.6 ± 11.6° to 9.4 ± 6.5° (P < .001). All patients had statistically significant (P < .001) improvement in mean International Knee Documentation Committee (IKDC) (44.9 ± 18.2 to 87.5 ± 6.9), Lysholm (61.4 ± 16.6 to 94.1 ± 6.4), Kujala (56.0 ± 16.8 to 92.9 ± 5.3), and Tegner score (2.7 ± 1.3 to 4.6 ± 1.4). The majority of patients (96.9%) returned to sports, with 90.3% returning to the same or greater level of activity. No postoperative dislocations or subluxations were reported. CONCLUSIONS: Arthroscopically assisted double-bundle MPFC-R is a promising procedure to treat recurrent patellar instability at 2- to 7-year mid-term follow-up, despite the presence of trochlear dysplasia, elevated TT-TG distance and patellar alta. The improvement of IKDC score exceeded the minimal clinically important difference in 95.2% patients, and 66.7% surpassed the patient acceptable symptomatic state based on postoperative IKDC score with no redislocations being reported at latest follow-up. LEVEL OF EVIDENCE: Level IV, case series, retrospective.

Comparison and analysis of skiing injuries at ski resorts in Chongli, China and Japan.

PURPOSE: The rapid development of winter sports requires investigation on injuries in Chongli district, Zhangjiakou city, one of the ski sites of the 2022 Winter Olympics. Careful evaluation is required to observe which injuries are caused under what circumstances, and then we can make corresponding preventive measures and recommendations based on the results. METHODS: In this retrospective study, the data of injury cases at ski resorts in China (Chongli district) and Japan were analyzed to provide a reference for the ongoing injury prevention at ski resorts. We collected data on injuries at Wanlong and Fulong ski resorts in Chongli district during the 2017-2018 and 2018-2019 ski seasons. We referred to the skiing injury report issued in February 2020 of a nationwide ski safety statistical service - Japan Ski Safety Association. The causes of injury and specific injured body parts were analyzed based on the data of Chinese and Japanese ski resorts. Statistical significance has been calculated using the Chi-square test. RESULTS: During the 2019-2020 ski season in Japanese ski resorts, the number of reported injuries per 10,000 skiers was 0.93, of which 457 (17.3%) were over 50 years old, accounting for a large proportion of injuries, meanwhile in Chongli ski resort, the injury rate of skiers aged 50 and over was 7.1%. The knee joint (23.7% at Wanlong ski resort and 28.4% in Japanese ski resorts) was the most injured body part among Chongli and Japanese skiers. Among snowboarders, shoulder joint injury (17.7% in Japanese ski resorts) was the most common, and injury on hands and fingers (16.3% in Wanlong ski resorts) was the most common. Head injury rates are similar in Chongli, China and Japanese ski resorts (8.2% and 8.7%, respectively). CONCLUSION: Our analysis demonstrated that injury data recorded among young skiers was higher in Chinese ski resorts (Chongli district) than that in Japanese ski resorts, and elderly skiers made up a larger proportion of skiing injuries in Japanese resorts. Thus, according to our research, the protection of knee joints, shoulder joints, and hands and fingers should be taken seriously. It should pay attention to the teaching of ski poles (for finger protection), and use protective devices such as knee pads, helmets, etc.

Outcomes After Hip Arthroscopy for Femoroacetabular Impingement Syndrome in Chinese Patients: A Minimum 2-Year Follow-up Study.

Background: Most of the research data of arthroscopic treatment for femoroacetabular impingement syndrome (FAIS) have been generated from Western populations. Purpose: To report the minimum 2-year follow-up results after hip arthroscopy for FAIS in Chinese patients. Study Design: Case series; Level of evidence, 4. Methods: A total of 434 hips that underwent primary hip arthroscopy for FAIS between 2016 and 2018 were included. Excluded were patients with previous ipsilateral hip surgery, ipsilateral surgery during the follow-up time, preoperative lateral center-edge angle <25°, Tönnis grade ≥2, sacroiliac joint disease, or incomplete preoperative radiographs or medical records. Preoperative and postoperative patient-reported outcomes (PROs; modified Harris Hip Score [mHHS], Hip Outcome Score-Activities of Daily Living [HOS-ADL], international Hip Outcome Tool, 12-component form [iHOT-12], and visual analog scale [VAS] for pain) were compared with the 2-tailed paired Student t test. Radiographic measures, intraoperative findings, performed procedures, complications, and revision surgery were also reported. The Spearman rank correlation was used to determine the association between patient characteristics and improvement in PRO scores. Results: Included were 272 hips with a mean follow-up of 39.4 ± 8.1 months. Overall, 243 hips (89.3%) underwent labral repair. The PROs from baseline to final follow-up were 64.7 to 90.0 for HOS-ADL, 41.1 to 73.4 for iHOT-12, 62.8 to 89.6 for mHHS, and 6.1 to 1.7 for VAS (P < .001 for all). Younger age was correlated significantly with improved iHOT-12 scores (r = -0.230; P < .001), and shorter symptom duration was significantly correlated with improved HOS-ADL (r = -0.190; P = .003), iHOT-12 (r = -0.146; P = .024), and VAS pain (r = -0.143; P = .027) scores. The overall complication and revision hip arthroscopy rates were 4.0% and 3.3% respectively. At the final follow-up, no patient required conversion to total hip arthroplasty (THA). Conclusion: At 2 years after hip arthroscopy for FAIS, Chinese patients demonstrated statistically significant improvement in PROs, with a low rate of revision surgery or conversion to THA. Shorter symptom duration and younger age were significantly positively correlated with improvement in PROs.

Prenatal smoke (Nicotine) exposure and offspring's metabolic disease susceptibility in adulthood.

Exposure to smoking (nicotine) during pregnancy not only directly affects fetal development, but also increases susceptibility to metabolic diseases in adulthood, but the mechanism of action remains unclear. Here, we review epidemiological and laboratory studies linking these relationships. In addition to the direct effect of nicotine on the fetus, intrauterine neuroendocrine-metabolic programming mediated by maternal glucocorticoid overexposure also plays an important role, involving glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis, hypothalamic-pituitary-adrenal (HPA) axis, renin-angiotensin system (RAS) and other endocrine systems. Epigenetics is involved in intrauterine neuroendocrine-metabolic programming, metabolic disease susceptibility and multigenerational inheritance. There are "two programming" and "two strikes" mechanisms for the occurrence of fetal-originated metabolic diseases in adulthood. These innovative research summaries and academic viewpoints provide experimental and theoretical basis for systematically elucidating the occurrence and development of fetal-originated metabolic diseases.

Prenatal caffeine exposure induced renal developmental toxicity and transgenerational effect in rat offspring.

Epidemiological studies revealed that prenatal caffeine exposure (PCE) is associated with adverse gestational outcomes and susceptibility to chronic diseases in offspring, yet the effects of PCE on glomerulosclerosis susceptibility in adult female offspring and its intergenerational transmission remain to be further investigated. Here, we found that PCE caused fetal kidney dysplasia and glomerulosclerosis of the female offspring. Besides, the kidney of F1 offspring in PCE group exhibited the "low expressional programming of AT2R" and "GC-IGF1 programming" alteration. Intergenerational genetic studies revealed that the renal defect and GC-IGF1 programming alteration was inherited to F2 adult female offspring derived from the female germ line, but Low expression of AT2R did not extend to the F2 female offspring. Taken together, PCE caused renal dysplasia and adult glomerulosclerosis in the F1 female offspring, which might be mediated by renal AT2R low expressional programming and GC-IGF1 axis alteration. Furthermore, PCE induced transgenerational toxicity on kidney, and GC-IGF1 programming alteration might be the potential molecular mechanism. This study provided experimental evidence for the mechanism study of the intergenerational inheritance of kidney developmental toxicity caused by PCE.

Arthroscopic modified Broström procedure achieves faster return to sports than open procedure for chronic ankle instability.

PURPOSE: To compare the clinical outcomes, rate of return to sports, postural control, and muscle strength between the arthroscopic and open modified Broström procedure for chronic lateral ankle instability (CLAI) patients. METHODS: From September 2018 to April 2019, 70 patients diagnosed with CLAI were prospectively included with arthroscopic modified Broström procedure (n = 36) and open modified Broström procedure (n = 34). They were evaluated at five time points (preoperation and 3 months, 6 months, 1 year and 2 years postoperatively). The main results examined the rate of return to sports, American Orthopaedic Foot and Ankle Society Score (AOFAS), Foot and Ankle Ability Measure (FAAM), visual analogue scale (VAS), centre of pressure (COP) excursion velocity, time to boundary (TTB), plantar pressure, isokinetic muscle strength and complications. RESULTS: Compared with the open group, the arthroscopic group demonstrated a significantly shorter period of return to the preinjury sport (13.2 ± 2.4 weeks vs. 18.7 ± 3.1 weeks, P = 0.023) and a higher early sport ratio (80.6 vs. 61.8%, P = 0.011) combined with better FAAM sports and AOFAS at 3 months and 6 months postoperatively and VAS at 3 months postoperatively. In addition, better anterior-posterior postural control stability, less time to peak force under lateral hindfoot and better dorsiflexion strength were shown in the arthroscopic group at 6 months postoperatively. No significant difference was found in clinical scores, posture control or muscle strength at the 1- or 2-year follow-up between the two groups. CONCLUSIONS: Shorter period and higher rates of return to sport activities and better clinical scores, posture control and muscle strength were achieved in the arthroscopic group at 6 months postoperatively, and no clinical differences were found between arthroscopic and open modified Broström procedure 1 year or 2 years postoperatively. Arthroscopic modified Broström procedure is a reliable procedure for CLAI injuries with the demand for fast exercise recovery. CLINICAL REGISTRATION: ChiCTR1900023999. LEVEL OF EVIDENCE: II.

Delayed Wound Healing After Achilles Tendon Suture: An Arthroscopic Solution.

This technical note describes an arthroscopic technique for treating delayed wound healing after Achilles tendon suture. Ankle arthroscopy is used to clean up the inflammatory tissues and foreign bodies that lead to delayed wound healing, with the advantages of simple postoperative care and low infection risk. This method may provide a less traumatic and low-risk option for the treatment of delayed wound healing after Achilles tendon surgery. The purpose of this technical note is to describe surgical procedures and related recommendations.

The effectiveness and sustainability of supervised balance training in chronic ankle instability with grade III ligament injury: a one-year prospective study.

BACKGROUND: To determine the effectiveness and sustainability of supervised balance training in people with chronic ankle instability (CAI) with grade III ligament injury. METHODS: Twenty young adults (12 males and 8 females) diagnosed with CAI with grade III ligament injury underwent 3 months of supervised balance training. The self-reported functional questionnaire, plantar pressure (walking and single leg standing), and isokinetic ankle strength were consecutively evaluated at pre-training, 3 months, 6 months and one year. Paired T tests were used to explore changes in muscle strength and plantar pressures following the supervised balance training. According to whether the patient had sprain recurrence, the patients were divided into sprain recurrence group and control group. The risk factors of sprain recurrence were explored with univariate analysis and multivariable logistic regression. RESULTS: The self-reported functional scores, the plantar pressure distribution and the muscle strength showed significant immediate improvements after 3 months of supervised balance training. At 6 months post-training, peak force under 2nd metatarsal, time to peak force under the medial hindfoot, time to boundary measurements and dorsiflexion, and eversion strength were partly declined to the pre-training level. 16 patients (80%) resumed the daily life and sports without sprain recurrence during the follow-up. Four patients (20%) reported ankle sprain during the follow-up, and the sprain recurrence group showed significantly higher Beighton scores (p = 0.012) and weaker initial inversion strength (p = 0.022) than the control group. CONCLUSIONS: Three months' of supervised balance training could effectively improve postural control and muscle strength of CAI cases with grade III ligament injury, although these improvements would partially deceased over time. Additional strength exercises for dorsiflexion and eversion should be supplemented from 6 months. Higher Beighton score and initial inversion muscle strength weakness might increase the risk of sprain recurrence. TRIAL REGISTRATION: ChiCTR, ChiCTR1900023999, Registered 21 June 2019, https://www.chictr.org.cn/edit.aspx?pid=39984&htm=4.

Meniscus repair with simultaneous anterior cruciate ligament reconstruction: Clinical outcomes, failure rates and subsequent processing.

PURPOSE: To retrospectively analyze the clinical outcomes of meniscus repair with simultaneous anterior cruciate ligament (ACL) reconstruction and explore the causes of failure of meniscus repair. METHODS: From May 2013 to July 2018, the clinical data of 165 patients who were treated with meniscus surgery and simultaneous ACL reconstruction, including 69 cases of meniscus repair (repair group) and 96 cases of partial meniscectomy (partial meniscectomy group) were retrospectively analyzed. The exclusion criteria were as follows: (1) ACL rupture associated with fracture, collateral ligament injury, or complex ligament injury; (2) a history of knee surgery; or (3) a significant degree of osteoarthritis. The 69 patients in the repair group were divided into the non-failure group (62 cases) and the failure group (7 cases) depending on the repair effect. Postoperative outcomes of the repair group and the partial meniscectomy group were compared. General conditions and postoperative outcomes of the failure group and the non-failure group were compared. During the median follow-up period of 28 months (range, 4 - 65 months) after the second arthroscopy, postoperative outcomes of seven patients in the failure group were summarized. SPSS 25.0 statistical software was used for statistical analysis. A p value less than 0.05 was considered statistically significant. RESULTS: Seven patients in the failure group who underwent the second arthroscopy were followed up for (30 ± 17.4) months and their postoperative outcomes were summarized. Compared with the partial meniscectomy group, the International Knee Documentation Committee scores of patients in the repair group improved significantly (p = 0.031). Compared with the non-failure group, more patients in the failure group were younger than 24 years (p = 0.030). The median follow-up period was 39.5 months. All patients recovered well after subsequent partial meniscectomy and relieved clinical symptoms. Visual analog scale scores decreased significantly (p = 0.026), and the International Knee Documentation Committee and Lysholm scores improved significantly (p = 0.046 for both). CONCLUSION: The failure rate of meniscus repair in this study was 10.1% (7/69), all of which were medial meniscus tears. However, the surgical outcomes of ACL reconstruction were not affected, and there might be a role for graft protection. Therefore, meniscus retears can be successful treated by performing subsequent partial meniscectomy in patients with repair failure.

The selection and identification of compound housekeeping genes for quantitative real-time polymerase chain reaction analysis in rat fetal kidney.

During quantitative real-time polymerase chain reaction (RT-qPCR) data analysis, the selection of optimal housekeeping gene is necessary to ensure the accuracy of results. It is noteworthy that housekeeping genes commonly used in adult studies may not be applicable for fetus. However, the stability analysis of housekeeping gene in fetal kidney has not been reported. This study intends to screen the applicable compound housekeeping genes in rat fetal kidney. In this study, eight housekeeping genes used in kidney studies based on literature reports (GAPDH, ACTB, 18S, HPRT, YWHAZ, HMBS, PPIA, and TBP) were selected as the research object. Their expression levels in the rat fetal kidney in physiological condition and the intrauterine growth retardation (IUGR) model induced by prenatal dexamethasone exposure (PDE) (0.2 mg/kg·day from gestation Days 9 to 20) was measured. Furthermore, these eight housekeeping genes were used to conduct relative quantitative analysis of nephrin expression in the fetal kidney in PDE-induced IUGR model, to compare the influence of choosing different housekeeping gene on data analysis of nephrin expression and to verify the reliability of selected compound housekeeping genes. In this study, stable housekeeping genes of fetal kidney tissues in PDE-induced IUGR model were identified: ACTB, GAPDH, TBP, and HMBS for males; ACTB, YWHAZ, and GAPDH for females. Besides, our results suggest that ACTB + GAPDH were the best compound housekeeping genes for normalization analysis in male fetal kidney studies, and ACTB + YWHAZ in females. This study will provide an experimental evidence basis for the selection of housekeeping genes in the RT-qPCR experiment in renal development toxicology-related models.

Intergenerational genetic programming mechanism and sex differences of the adrenal corticosterone synthesis dysfunction in offspring induced by prenatal ethanol exposure.

We previously found that prenatal ethanol exposure (PEE) induced adrenal dysplasia in offspring, which was related to intrauterine maternal glucocorticoid overexposure. This study investigated the intergenerational genetic effect and sex differences of PEE-induced changes in the synthetic function of adrenal corticosterone in offspring, and to clarify the intrauterine origin programming mechanism. Wistar pregnant rats were gavaged with ethanol (4 g/kg bw/d) from gestation day (GD) 9-20, and F1 generation was born naturally. The F1 generation female rats in the PEE group were mated with normal male rats to produce F2 generation. Serum and adrenal glands of fetal rats and F1/F2 adult rats were collected at GD20 and postnatal week 28. PEE increased the serum corticosterone level, while diminishing the expression of adrenal steroid synthases of fetal rats. Moreover, PEE enhanced the mRNA expression of GR and HDAC1, but inhibited the mRNA expression of SF1 and reduced the H3K9ac level of P450scc in the fetal adrenal gland. In PEE adult offspring of F1 and F2 generation the serum corticosterone level, the H3K9ac level of P450scc and its expression were decreased in males but were increased in females. In NCI-H295R cells, cortisol reduced the production of endogenous cortisol, down-regulated SF1, and up-regulated HDAC1 expression by activating GR, and decreased H3K9ac level and expression of P450scc. In conclusion, PEE could induce adrenal dysplasia in offspring with sex differences and intergenerational genetic effects, and the adrenal insufficiency in male offspring was related to the induction of low functional genetic programming of P450scc by intrauterine high corticosterone through the GR/SF1/HDAC1 pathway.