Pioglitazone Antagonized the Effects of Advanced Glycation End Products on Achilles Tendon Healing and Improved the Recovery of Tendon Biomechanical Properties.

Purpose: Advanced glycation end products (AGEs) often accumulate in the Achilles tendon during the course of diabetes. This study aims to determine the impact of AGEs on tendon repair and explore the role of pioglitazone in mitigating this impact. Methods: Forty-eight male 8 week-old Sprague Dawley rats were selected in this study. After transection of Achilles tendon, the rats were randomly divided into four groups. The Achilles tendons of rats were injected with 1000 mmol/L D-ribose to elevate the content of AGEs within the tendons in two groups, the remaining two groups received injections of phosphate buffered saline (PBS) solution. Subsequently, the first two groups were respectively received oral administration of pioglitazone (20 mg/kg/day) and PBS. The remaining two groups were given the same treatment. The expression of the collagen-I, TNF-α, IL-6 of the repaired tendon were detected. The macroscopic, pathologic and biomechanical aspects of tendon healing were also evaluated. Results: AGEs accumulation in tendon during the healing process increases the expression of inflammatory factors such as TNF-α and IL-6, leading to insufficient synthesis of collagen-I and delayed recovery of the tendon's tensile strength. Pioglitazone significantly attenuated the damage caused by AGEs to the tendon healing process, effectively improving the recovery of tendon tensile strength. Pioglitazone could not inhibit the generation of AGEs in the tissue and also had no impact on the normal healing process of the tendon. Conclusions: Pioglitazone could prevent the deleterious impact of AGEs on the Achilles tendon healing and improve the biomechanical properties of the tendon.

An in-vitro three-dimensional surgical simulation technique to predict tibial tunnel length in transtibial posterior cruciate ligament reconstruction.

BACKGROUND: During the transtibial posterior cruciate ligament (PCL) reconstruction, drilling depth excessively longer than the tibial tunnel length (TTL) is an important reason to cause popliteal neurovascular bundle injury when preparing the tibial tunnel. This study aims to develop an in-vitro three-dimensional surgical simulation technique to determine the TTL in anteromedial (AM) and anterolateral (AL) approaches. METHODS: A total of 63 knees' 3-dimensional (3D) computed tomography models were included in this study. The SuperImage system was used to reconstruct the 3D knee model and locate the tibial PCL site. The established 3D knee model and the coordinates of the tibial PCL site were imported into Rhinoceros 3D modeling software to simulate AM and AL tibial tunnel approaches with different tibial tunnel angles (TTA). The TTL and the tibial tunnel height (TTH) were measured in this study. RESULTS: In AM and AL tibial tunnel approaches, the TTL showed a strong correlation with the TTA (for AM: r = 0.758, p < 0.001; for AL: r = 0.727, p < 0.001). The best fit equation to calculate the TTL based on the TTA was Y = 1.04X + 14.96 for males in AM approach, Y = 0.93X + 17.76 for males in AL approach, Y = 0.92X + 14.4 for females in AM approach, and Y = 0.94X + 10.5 for females in AL approach. CONCLUSION: Marking the TTL on the guide pin or reamer could help to avoid the drill bit over-penetrated into the popliteal space to damage the neurovascular structure.

Cryo-EM structures of the human NaS1 and NaDC1 transporters revealed the elevator transport and allosteric regulation mechanism.

The solute carrier 13 (SLC13) family comprises electrogenic sodium ion-coupled anion cotransporters, segregating into sodium ion-sulfate cotransporters (NaSs) and sodium ion-di- and-tricarboxylate cotransporters (NaDCs). NaS1 and NaDC1 regulate sulfate homeostasis and oxidative metabolism, respectively. NaS1 deficiency affects murine growth and fertility, while NaDC1 affects urinary citrate and calcium nephrolithiasis. Despite their importance, the mechanisms of substrate recognition and transport remain insufficiently characterized. In this study, we determined the cryo-electron microscopy structures of human NaS1, capturing inward-facing and combined inward-facing/outward-facing conformations within a dimer both in apo and sulfate-bound states. In addition, we elucidated NaDC1's outward-facing conformation, encompassing apo, citrate-bound, and N-(p-amylcinnamoyl) anthranilic acid (ACA) inhibitor-bound states. Structural scrutiny illuminates a detailed elevator mechanism driving conformational changes. Notably, the ACA inhibitor unexpectedly binds primarily anchored by transmembrane 2 (TM2), Loop 10, TM11, and TM6a proximate to the cytosolic membrane. Our findings provide crucial insights into SLC13 transport mechanisms, paving the way for future drug design.

Accuracy of detecting burst of the lateral wall in intertrochanteric hip fractures with plain radiographs: Is postoperative CT necessary?

Background: Postoperative burst of the lateral femoral wall is thought to be the main predictor of reoperation for intertrochanteric fractures, which is routinely evaluated using plain radiographs. We retrospectively compared computed tomography (CT) scans and radiographs regarding the ability to detect burst of the lateral wall. We also investigated whether intramedullary nails may cause iatrogenic burst of the lateral wall. Methods: From January 2010 to December 2021, patients aged 65 years and older who undergone intertrochanteric fractures treated with the proximal femoral nail antirotation 2 (PFNA-Ⅱ) were included. The incidence of burst of the lateral wall was evaluated with two different imaging modalities by two observers. Two rounds of evaluation were performed: (1) with plain radiographs alone; and (2) with CT scans combined with radiographs. Interobserver and intraobserver agreement (κ value) for evaluation of the lateral wall burst was assessed. Results: A total of 1507 patients were included (362 males and 1145 females). Compared with radiographs alone (12.0 %, 181/1507 patients), a higher rate of lateral wall burst was found by CT scans combined with radiographs (72.9 %, 1098/1507 patients) for observer 1 at first reading (P < 0.001). Similar results were seen in other evaluations. Interobserver and intraobserver agreement was substantial for radiographs alone (κ, 0.659-0.727) and almost perfect for CT scans combined with radiographs (κ, 0.847-0.926). Conclusions: Computed tomography combined with radiographs is superior to radiographs alone for detecting burst of the lateral wall after intertrochanteric fracture fixation. Additionally, PFNA-Ⅱ could cause iatrogenic burst of the lateral wall for intertrochanteric fractures in the elderly.

The cryo-EM structure of homotetrameric attachment glycoprotein from langya henipavirus.

Langya Henipavirus (LayV) infection is an emerging zoonotic disease that has been causing respiratory symptoms in China since 2019. For virus entry, LayV's genome encodes the fusion protein F and the attachment glycoprotein G. However, the structural and functional information regarding LayV-G remains unclear. In this study, we revealed that LayV-G cannot bind to the receptors found in other HNVs, such as ephrin B2/B3, and it shows different antigenicity from HeV-G and NiV-G. Furthermore, we determined the near full-length structure of LayV-G, which displays a distinct mushroom-shaped configuration, distinguishing it from other attachment glycoproteins of HNV. The stalk and transmembrane regions resemble the stem and root of mushroom and four downward-tilted head domains as mushroom cap potentially interact with the F protein and influence membrane fusion process. Our findings enhance the understanding of emerging HNVs that cause human diseases through zoonotic transmission and provide implication for LayV related vaccine development.

The potential role of minimal/molecular residual disease in colorectal cancer: curative surgery, radiotherapy and beyond.

Detection of minimal/molecular residual disease (MRD) based on ctDNA assay develops from hematological malignancies to solid tumors. Generally, there are two mainstream assays in MRD testing technology: tumor-informed and tumor-agnostic. For colorectal cancer (CRC), MRD is used not only to monitor recurrence and predict prognosis, but also to help in clinical decision making and assessment of clinical efficacy in the settings of curative surgery, radiotherapy, chemotherapy and surveillance. Accumulated clinical trials are exploring roles of MRD in early or advanced stages of CRC. Here, we give an overview of how MRD is and will be used in CRC.

[Clinical application of penile biological vibration threshold for precise use of 5% lidocaine cream to treat hypersensitive premature ejaculation].

OBJECTIVE: This study aimed to evaluate the efficacy and safety of applying 5% lidocaine cream to the sensitive area of the glans penis after its precise localization under the penile biological vibration threshold test for the treatment of primary premature ejaculation. METHODS: Eighty patients diagnosed with primary premature ejaculation in an outpatient setting were included in this study. They were randomly scored into two groups. Group 1 (n = 40) was given 1 ml of 5% lidocaine cream on demand. They were instructed to apply the lidocaine cream evenly in a circular pattern to the glans penis without precise application to the sensitive area of the glans penis. The treatment lasted for a total of 4 weeks. Group 2 (n = 40) had a penile biological vibration threshold test performed to detect loci with a lower threshold. They were instructed to apply 1 ml of 5% lidocaine cream to the sensitive loci on the glans penis for 4 weeks. Lidocaine cream was applied topically or uniformly to the glans penis 20 minutes before planned intercourse in both groups .The efficacy and side effects before and after treatment were evaluated by the intravaginal ejaculation latency (IELTs) before and after treatment, combined with the Arabic Index of Premature Ejaculation and IIEF-5 score. RESULTS: After treatment, IELTs in both groups were significantly improved compared with those before treatment(P<0.05);The Arab premature ejaculation index and IIEF-5 score of the precise smear group are higher than those of the uniform smear group(P<0.05). CONCLUSION: This study infers that applying lidocaine according to the threshold of penile and glans vibration has a positive effect and fewer adverse event reports compared with the traditional method of using surface anesthetics, which is worthy of clinical promotion.

Traditional chinese medicine to prevent and treat diabetic erectile dysfunction.

Diabetic erectile dysfunction (DED) is one of the most common complications of diabetes mellitus. However, current therapeutics have no satisfactory effect on DED. In recent years, traditional Chinese medicine (TCM) has shown good effects against DED. By now, several clinical trials have been conducted to study the effect of TCM in treating DED; yet, the underlying mechanism is not fully investigated. Therefore, in this review, we briefly summarized the pathophysiological mechanism of DED and reviewed the published clinical trials on the treatment of DED by TCM. Then, the therapeutic potential of TCM and the underlying mechanisms whereby TCM exerts protective effects were summarized. We concluded that TCM is more effective than chemical drugs in treating DED by targeting multiple signaling pathways, including those involved in oxidation, apoptosis, atherosclerosis, and endothelial function. However, the major limitation in the application of TCM against DED is the lack of a large-scale, multicenter, randomized, and controlled clinical trial on the therapeutic effect, and the underlying pharmaceutical mechanisms also need further investigation. Despite these limitations, clinical trials and further experimental studies will enhance our understanding of the mechanisms modulated by TCM and promote the widespread application of TCM to treat DED.

[Male infertility and urologic cancers: Advances in studies].

Male infertility is one of the most common diseases in andrology. Studies show that male infertility is significantly correlated with the incidence and mortality of tumors, especially malignant tumors in the genitourinary system, such as testis cancer and prostate cancer. The relationship of male infertility with genitourinary system tumors involves various aspects, mainly including changes in chromosome mutations, epigenetic marks, hormonal imbalance, and congenital deformity. Besides, some chronic diseases are shown to be significantly associated with male infertility, and semen quality or fertility status may be biomarkers of the overall health of males. In-depth studies of the correlation between male infertility and these factors are very important for an insight into the pathogenesis and prevention of the related diseases.