Effect of cytochrome P450 3A4 on tissue distribution of humantenmine, koumine, and gelsemine, three alkaloids from the toxic plant Gelsemium.

Humantenmine, koumine, and gelsemine are three indole alkaloids found in the highly toxic plant Gelsemium. Humantenmine was the most toxic, followed by gelsemine and koumine. The aim of this study was to investigate and analyze the effects of these three substances on tissue distribution and toxicity in mice pretreated with the Cytochrome P450 3A4 (CYP3A4) inducer ketoconazole and the inhibitor rifampicin. The in vivo test results showed that the three alkaloids were absorbed rapidly and had the ability to penetrate the blood-brain barrier. At 5 min after intraperitoneal injection, the three alkaloids were widely distributed in various tissues and organs, the spleen and pancreas were the most distributed, and the content of all tissues decreased significantly at 20 min. Induction or inhibition of CYP3A4 in vivo can regulate the distribution and elimination effects of the three alkaloids in various tissues and organs. Additionally, induction of CYP3A4 can reduce the toxicity of humantenmine, and vice versa. Changes in CYP3A4 levels may account for the difference in toxicity of humantenmine. These findings provide a reliable and detailed dataset for drug interactions, tissue distribution, and toxicity studies of Gelsemium alkaloids.

Towards a global partnership model in interprofessional education for cross-sector problem-solving.

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.

Network Pharmacology and Experimental Verification to Unveil the Mechanism of N-Methyl-D-Aspartic Acid Rescue Humantenirine-Induced Excitotoxicity.

Gelsemium is a medicinal plant that has been used to treat various diseases, but it is also well-known for its high toxicity. Complex alkaloids are considered the main poisonous components in Gelsemium. However, the toxic mechanism of Gelsemium remains ambiguous. In this work, network pharmacology and experimental verification were combined to systematically explore the specific mechanism of Gelsemium toxicity. The alkaloid compounds and candidate targets of Gelsemium, as well as related targets of excitotoxicity, were collected from public databases. The crucial targets were determined by constructing a protein-protein interaction (PPI) network. Subsequently, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the bioprocesses and signaling pathways involved in the excitotoxicity corresponding to alkaloids in Gelsemium. Then, the binding affinity between the main poisonous alkaloids and key targets was verified by molecular docking. Finally, animal experiments were conducted to further evaluate the potential mechanisms of Gelsemium toxicity. A total of 85 alkaloids in Gelsemium associated with 214 excitotoxicity-related targets were predicted by network pharmacology. Functional analysis showed that the toxicity of Gelsemium was mainly related to the protein phosphorylation reaction and plasma membrane function. There were also 164 pathways involved in the toxic mechanism, such as the calcium signaling pathway and MAPK signaling pathway. Molecular docking showed that alkaloids have high affinity with core targets, including MAPK3, SRC, MAPK1, NMDAR2B and NMDAR2A. In addition, the difference of binding affinity may be the basis of toxicity differences among different alkaloids. Humantenirine showed significant sex differences, and the LD50 values of female and male mice were 0.071 mg·kg-1 and 0.149 mg·kg-1, respectively. Furthermore, we found that N-methyl-D-aspartic acid (NMDA), a specific NMDA receptor agonist, could significantly increase the survival rate of acute humantenirine-poisoned mice. The results also show that humantenirine could upregulate the phosphorylation level of MAPK3/1 and decrease ATP content and mitochondrial membrane potential in hippocampal tissue, while NMDA could rescue humantenirine-induced excitotoxicity by restoring the function of mitochondria. This study revealed the toxic components and potential toxic mechanism of Gelsemium. These findings provide a theoretical basis for further study of the toxic mechanism of Gelsemium and potential therapeutic strategies for Gelsemium poisoning.

Endoscopic Treatment of Recurred External Snapping Hip After Endoscopic Iliotibial Band Release.

External snapping hip is caused by snapping of the thickening of the posterior portion of the iliotibial band or the anterior border of the gluteus maximus over the greater trochanter. Surgery is considered for patients who are refractory to conservative treatment. The endoscopic release of the iliotibial band or the endoscopic release of the femoral insertion of the gluteus maximus tendon is the most popular technique. There is a recurrence rate of 7-29% after endoscopic surgery. Although recurrence is often painless, revision surgery may be indicated for symptomatic recurrence. In this Technical Note, the technical details of endoscopic treatment of recurred external snapping hip after endoscopic iliotibial band release. The key to success is adequate release of the iliotibial band, gluteus maximus tendon, and the fibrosis underneath the iliotibial band.

Arthroscopic Revision of Attenuated Anterior Cruciate Ligament Graft With Enlarged Bone Tunnels Using Injectable Bone Graft Substitute.

Revision anterior cruciate ligament (ACL) reconstruction is a technically demanding procedure, and the surgeon should be prepared to address bone tunnel osteolysis, concurrent meniscal, ligamentous, or cartilage lesions, and limb malalignment. ACL revision can typically be done in one procedure, but it may need to be staged if there is poor previous tunnel positioning or excessive tunnel osteolysis. Bone grafting of the tunnels can be accomplished in several ways, including autograft, allograft, or bone substitutes. Currently, no consensus is available regarding the optimal choice of bone graft material for bone tunnel augmentation in revision ACL reconstruction. Bone graft substitute for tunnel augmentation has been showed to have good histologic, radiographic, and intraoperative integration, comparable to that of autologous bone. In this Technical Note, the technical details of arthroscopic treatment of attenuated anterior cruciate ligament graft with enlarged bone tunnels are described. The tunnels are debrided arthroscopically and filled up with PRO-DENSE injectable regenerative graft.

Phosphoproteomics reveals NMDA receptor-mediated excitotoxicity as a key signaling pathway in the toxicity of gelsenicine.

Gelsenicine is one of the most toxic compounds in the genus Gelsemium, but the mechanism of toxicity is not clear. In this paper, tandem mass tag quantitative phosphoproteomics was used to study the changes in protein phosphorylation in different brain regions at different time points after gelsenicine poisoning in mice. The correlation between neurotransmitter receptors and the toxicity of gelsenicine was analyzed by molecular docking and rescue experiments. Parallel reaction monitoring (PRM) was used to verify the related proteins. A total of 17877 unique phosphosites were quantified and mapped to 4170 brain proteins to understand the signaling pathways. Phosphoproteomics revealed gelsenicine poisoning mainly affected protein phosphorylation levels in the hippocampus, and through bioinformatics analysis, it was found gelsenicine poisoning significantly affected neurotransmitter synaptic pathway. The molecular docking results showed that gelsenicine could bind to the N-methyl-D-aspartic acid receptor (NMDAR). In addition, we found that NMDA was effective in improving the survival rate of the animals tested, and this effect was associated with reduced protein phosphorylation by PRM validation. The results revealed that gelsenicine affects neurotransmitter release and receptor function. This is the first demonstration that NMDA receptor-mediated excitotoxicity is a key signaling pathway in the toxicity of gelsenicine.

Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase.

Background: Macleaya cordata (Willd.) (Papaveraceae) is listed as a feed additive in animal production by the European Food Authority. Methods: The metabolites of chelerythrine in rats were measured in vitro and in vivo by rapid and accurate high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). The structures of CHE metabolites were elucidated by comparing their changes in accurate molecular masses and fragment ions with those of parent ion or metabolite. The metabolic enzymes that were involved in chelerythrine reduction were investigated using an inhibition method. The tissue distribution of chelerythrine and the effects on NQO1 following intragastric administration with M. cordata extracts in rats were examined. Results: A total of twelve metabolites of chelerythrine were characterized by this approach in rat liver S9 and in vivo. The reduction of the iminium bond of chelerythrine and subsequent O-demethylation was the main metabolic pathway of chelerythrine in rat liver S9 while the reduction of the iminium bond of chelerythrine was the main metabolic pathway of chelerythrine in rats in vivo. After the rats were given intragastric administration, the low concentration residues of sanguinarine and chelerythrine in different rat tissues were found at 48 h after the last dose, suggesting that both compounds could be widely distributed in tissues. The results also indicated that XO, NQO1, NQO2, and carbonyl reductase are involved in chelerythrine reduction. Macleaya cordata extracts treated female and male rats, respectively, showed different responses, inhibiting NQO1 activity in males, but inducing NQO1 activity in females. Chelerythrine had a weak impact on NQO1 activity, but sanguinarine inhibited NQO1 activity Conclusion: Through studying the effects of cytosolic reductase inhibitors on chelerythrine reduction and the impact of chelerythrine and sanguinarine on the activity of NQO1 in vitro and in vivo, we clarified the potential drug interaction of Macleaya cordata extract in clinical application, so as to provide theoretical guidance for clinically safe medication. In addition, it provided a reference basis for the metabolic mechanism of chelerythrinein rats.

Integration of Metabolomics and Transcriptomicsto Comprehensively Evaluate the Metabolic Effects of Gelsemium elegans on Pigs.

Some naturalphytogenic feed additives, which contain several active compounds, have been shown to be effective alternatives to traditional antibiotics. Gelsemium elegans (G. elegans) is a whole grass in the family Loganiaceae. It is a known toxic plant widely distributed in China and has been used as a traditional Chinese herbal medicine for many years to treat neuropathic pain, rheumatoid pain, inflammation, skin ulcers, and cancer. However, G. elegans not only is nontoxic to animals such as pigs and sheep but also has an obvious growth-promoting effect. To our knowledge, the internal mechanism of the influence of G. elegans on the animal body is still unclear. The goal of this work is to evaluate the metabolic consequences of feeding piglets G. elegans for 45 days based on the combination of transcriptomics and metabolomics. According to growth measurement and evaluation, compared with piglets fed a complete diet, adding 20 g/kg G. elegans powder to the basal diet of piglets significantly reduced the feed conversion ratio. Results of the liver transcriptome suggest that glycine and cysteine-related regulatory pathways, including the MAPK signaling pathway and the mTOR signaling pathway, were extensively altered in G. elegans-induced piglets. Plasma metabolomics identified 21 and 18 differential metabolites (p < 0.05) in the plasma of piglets in the positive and negative ion modes, respectively, between G. elegans exposure and complete diet groups. The concentrations of glycine and its derivatives and N-acetylcysteine were higher in the G. elegans exposure group than in the complete diet group.This study demonstrated that G. elegans could be an alternative to antibiotics that improves the immune function of piglets, and the latent mechanism of G. elegans may be related to various signaling pathways, including the MAPK signaling pathway and the PPAR signaling pathway.

A comprehensive toxicity evaluation in rats after long-term oral Gelsemium elegans exposure.

BACKGROUND: Gelsemium elegans (G. elegans) is a flowering plant of the Loganiaceae family, which had been used in traditional Chinese herb medicine for many years for the treatment of rheumatoid pain, neuropathic pain, spasticity, skin ulcers, anxiety and cancer. Acute toxicity of the plant severely limits the application and development of G. elegans; however, long-term toxicity of exposure to G. elegans has not been illuminated. PURPOSE: This study is a comprehensive observation of the effects of long-term exposure (21 days at 70 mg/kg) to G. elegans in rats. METHODS AND RESULTS: The histopathological examination showed only a mild glial cell proliferation in the brain, and no lesions were observed in other organs. No abnormal changes in the biochemical parameters were observed that would have significant effects. The identification and analysis of absorbed natural ingredients showed that the active ingredients of the G. elegans could distribute to various tissues, and six compounds were identified in the brain, suggesting that they could cross the blood-brain barrier. Based on the intestinal content metabolomics, the tryptophan (Trp) biosynthesis, bile acid synthesis and bile secretion pathways have attracted our attention. Plasma metabolomic results showed that uric acid (UA) was significantly increased. The results of the brain metabolomic tests showed that the level of pyridoxal (PL) was decreased; considering the expression levels of the related enzymes, it was hypothesized that the level of pyridoxal 5'-phosphate (PLP) was decreased. PLP was important for the regulation of the neuronal γ-aminobutyric acid (GABA)/glutamate (Glu) interconversion and therefore neuronal excitability. The data of the study suggested that toxic reaction caused by G. elegans was due to a disruption of the balance of the neurotransmitter GABA/Glu transformation. CONCLUSIONS: Overall, G. elegans did not cause significant toxic reaction in the rats after long-term exposure. The results were significant for the future clinical applications of G. elegans and suggested that G. elegans could be potentially developed as a drug. The study provided a scientific basis for investigation of the mechanisms of toxicity and detoxification.

Identification of Potential Dipeptidyl Peptidase (DPP)-IV Inhibitors among Moringa oleifera Phytochemicals by Virtual Screening, Molecular Docking Analysis, ADME/T-Based Prediction, and In Vitro Analyses.

Moringa oleifera Lam. (MO) is called the "Miracle Tree" because of its extensive pharmacological activity. In addition to being an important food, it has also been used for a long time in traditional medicine in Asia for the treatment of chronic diseases such as diabetes and obesity. In this study, by constructing a library of MO phytochemical structures and using Discovery Studio software, compounds were subjected to virtual screening and molecular docking experiments related to their inhibition of dipeptidyl peptidase (DPP-IV), an important target for the treatment of type 2 diabetes. After the four-step screening process, involving screening for drug-like compounds, predicting the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of pharmacokinetic properties, LibDock heatmap matching analysis, and CDOCKER molecular docking analysis, three MO components that were candidate DPP-IV inhibitors were identified and their docking modes were analyzed. In vitro activity verification showed that all three MO components had certain DPP-IV inhibitory activities, of which O-Ethyl-4-[(α-l-rhamnosyloxy)-benzyl] carbamate (compound 1) had the highest activity (half-maximal inhibitory concentration [IC50] = 798 nM). This study provides a reference for exploring the molecular mechanisms underlying the anti-diabetic activity of MO. The obtained DPP-IV inhibitors could be used for structural optimization and in-depth in vivo evaluation.

Pharmacokinetic Study of Multiple Components of Gelsemium elegans in Goats by Ultra-Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry.

Gelsemium elegans (G. elegans) has been used in traditional Chinese medicine. This plant is highly toxic to humans, but can promote the growth of pigs and goats in the veterinary clinic. It is a very complex mixture containing tens or hundreds of different components. Therefore, multiple-component pharmacokinetic studies of G. elegans are a major challenge due to the lack of authentic standards of the components. The purpose of this study was to investigate the plasma pharmacokinetics of multiple components after a single oral dose of G. elegans in goat using a sensitive ultra-performance liquid chromatography coupled to tandem mass spectrometry method for the simultaneous semiquantification of multiple alkaloids without standards. The method was validated in terms of the specificity, LOD, LOQ, linearity, accuracy, precision and matrix effects. To validate the global pharmacokinetic characteristics, the results obtained from the semiquantitative analysis of three authentic compounds (gelsemine, koumine and humantenmine) were compared with the absolute quantification from our recently published method. The results showed that the two methods had similar analytical results, and the obtained values of Tmax, T1/2 and MRT0-t of the three alkaloids were similar between the two methods. In addition, the values of Cmax and AUC0-t of the three alkaloids after normalization were close to the real values, which indicated that this semiquantitative method could be used in the pharmacokinetic study of multiplecomponents. Then the pharmacokinetic parameters of 23 other G. elegans alkaloids in goats were obtained. The results suggested that the gelsedine-type alkaloids were the major active ingredients that predict and explain the efficacy and toxicity of G. elegans.

The effect of preoperative short-term radiotherapy on postoperative complications in patients with rectal cancer / 中国医师进修杂志

Objective@#To investigate the effect of preoperative neoadjuvant short-term high-dose preoperative radiotherapy (RT) (5 × 5 Gy) on early postoperative complications in patients with locally advanced rectal adenocarcinoma.@*Methods@#The study period was January 2017 to June 2018. The total number of patients with locally advanced rectal adenocarcinoma who were treated in Cancer Hospital of the University of Chinese Academy of Sciences Zhejiang Cancer Hospital was 120 patients. They were divided into study group and control group according to the random number table method, 60 patients in each group; the study group received neoadjuvant radiotherapy (25 Gy, 5 divisions) before surgery, one week after surgery; the control group was treated immediately after tumor diagnosis; the surgical related indicators and postoperative complications, life function of the two groups were compared.@*Results@#In the study group, complete pathological reactions were observed in 9 patients (15.0%) (no cancer cells were found in tumor specimens), and 12 patients (20.0%) found residual cancer under the microscope; intraoperative sphincter retention study group and control group was 100.0%(60/60), 83.3%(50/60)100%, there was significant difference (P=0.002). Patients in the study group were significantly more likely to have metastasis than the control group [11.7%(7/60) vs. 5.0%(3/60)] (P=0.017). All metastasis oral cases were closed within 3-6 months after operation. There was no significant difference in the incidence of postoperative complications between the two groups, and the odds of primary anastomotic leakage was also basically the same. Life function analysis showed that the study group patients were significantly better than the control group in terms of overall health status, role function and social function.@*Conclusions@#Preoperative short-term RT in locally advanced rectal cancer does not increase the risk of postoperative complications and increase the chance of surgical preservation of the sphincter.

The effect of preoperative short-term radiotherapy on postoperative complications in patients with rectal cancer / 中国医师进修杂志

Objective To investigate the effect of preoperative neoadjuvant short-term high-dose preoperative radiotherapy (RT) (5 × 5 Gy) on early postoperative complications in patients with locally advanced rectal adenocarcinoma.Methods The study period was January 2017 to June 2018.The total number of patients with locally advanced rectal adenocarcinoma who were treated in Cancer Hospital of the University of Chinese Academy of Sciences Zhejiang Cancer Hospital was 120 patients.They were divided into study group and control group according to the random number table method,60 patients in each group;the study group received neoadjuvant radiotherapy (25 Gy,5 divisions) before surgery,one week after surgery;the control group was treated immediately after tumor diagnosis;the surgical related indicators and postoperative complications,life function of the two groups were compared.Results In the study group,complete pathological reactions were observed in 9 patients (15.0％) (no cancer cells were found in tumor specimens),and 12 patients (20.0％) found residual cancer under the microscope;intraoperative sphincter retention study group and control group was 100.0％(60/60),83.3％(50/60)100％,there was significant difference (P =0.002).Patients in the study group were significantly more likely to have metastasis than the control group [11.7％(7/60) vs.5.0％(3/60)] (P=0.017).All metastasis oral cases were closed within 3-6 months after operation.There was no significant difference in the incidence of postoperative complications between the two groups,and the odds of primary anastomotic leakage was also basically the same.Life function analysis showed that the study group patients were significantly better than the control group in terms of overall health status,role function and social function.Conclusions Preoperative short-term RT in locally advanced rectal cancer does not increase the risk of postoperative complications and increase the chance of surgical preservation of the sphincter.

Gene expression profile analysis of ileum transcriptomes in pigs fed Gelsemium elegans plants.

Gelsemium elegans is a flowering plant in the Loganiaceae. Because it can promote the growth of pigs and sheep, it is widely used, including in veterinary clinics, but little information is available about its biological effects. Here, we used high-throughput sequencing to characterize the differentially expressed genes (DEGs) in the ileums of pigs between a control group and a group fed Gelsemium elegans for 45 days. We found that Gelsemium elegans affected many inflammatory and immune pathways, including biological processes such as defense responses, inflammation and immune responses. Moreover, this study identified several important genes related to the anti-inflammatory activity of Gelsemium elegans (e.g., CXCL-8, IL1A, and CSF2), which will be beneficial for further study of the pharmacological mechanisms and clinical applications of Gelsemium elegans.

Comparing biomechanical strength of unicortical locking plate versus bicortical compression plate for transverse midshaft metacarpal fracture.

PURPOSE: Metacarpal bone fractures constitute 10% of all fractures. Unstable metacarpal fractures require surgical intervention, which poses danger to flexor tendon either due to bicortical drilling or construct of the implant. Unicortical locking plate fixation may be the solution to preventing flexor tendon injury. Studies have compared locking and compression plates. However, in these studies, the biomechanical properties were tested using the static loading method. This study looks into cyclical loading that is more representative of in vivo conditions, particularly for early rehabilitation. We compared the biomechanical strength of the unicortical locking plate and bicortical compression plate system in a transverse metacarpal fracture, tested with cyclical loading and torsion. METHOD: Twenty pieces of fourth-generation, biomechanical testing grade, left third metacarpal composite bones were used. Resin was used to create the holding block at both ends of the bone. An oscillating saw with 0.8 mm thick saw blade was used to osteotomize the metacarpal sawbones to create a midshaft transverse metacarpal fracture model. Ten pieces were fixed with a 2.0 mm titanium locking plate via unicortical screw purchase and 10 were fixed with a 2.0 mm, four holes, titanium dynamic compression plate, bicortical purchase of screws. They were subjected to cyclic load to failure testing three-point bending and torsion. RESULTS: There were no significant difference in stiffness and cyclic three-point bending to failure between the unicortical locking plate group and the bicortical compression plate group. The bicortical compression plate group is stiffer and has a higher cyclic bending load to failure as compared to the unicortical locking plate group. CONCLUSION: Unicortical locking plate fixation of metacarpal fracture can be reliably applied clinically to produce a strong and stable construct that allows early mobilization of the joints. This will not only reduce the complication rate of metacarpal plating, but also improve the functional outcome of the hand.

Cadaveric Study of the Junction Point Where the Gastrocnemius Aponeurosis Joins the Soleus Aponeurosis.

PURPOSE: To study the location of the junction point where the gastrocnemius aponeurosis joins the soleus aponeurosis to form the Achilles tendon. METHODS: Twelve lower limb specimens were used. The distance between the medial tibial plateau and the superior border of the posterior calcaneal tubercle (A) was measured and the distances of the junction point to the superior border of the posterior calcaneal tubercle (B) were measured. RESULT: The ratio B/A averaged 0.45. The gastrocnemius muscle reached or extended beyond the junction point in eight specimens (67%). The average distance from the lowest border of the muscle to the junction point was 0±12mm (-25-25). CONCLUSION: There are great anatomical variations of the gastrocnemius insertion. Resection of muscle bound portion of the gastrocnemius aponeurosis is a more appropriate approach of endoscopic gastrocnemius aponeurosis recession. CLINICAL RELEVANCE: This report suggests that resection of muscle bound portion rather than the muscle void portion of the gastrocnemius aponeurosis is a more appropriate approach of endoscopic gastrocnemius aponeurosis recession.

Peroneus Longus Tendoscopy at the Sole: A Cadaveric Study.

PURPOSE: The aim of this study was to investigate the safety of tendoscopy of the peroneus longus (PL) at the sole in a cadaveric model. METHODS: Twelve fresh-frozen foot and ankle specimens were used. The locations of the plantar medial and plantar lateral portals were studied. The relationships of the medial and lateral plantar nerves to the tendon sheath of the PL at the sole were also studied. RESULTS: The plantar lateral portal was located on average 11 mm (6 to 16 mm) proximal and 9 mm (6 to 15 mm) plantar to the fifth metatarsal styloid. The plantar medial portal was located on average 1 mm (12 mm proximal to the joint to 7 mm distal to the joint) proximal to the first tarsometatarsal joint. The lateral plantar nerve touched the PLT sheath in 8 specimens. The nerve was separated from the tendon sheath by a thin layer of muscle in 4 specimens. The medial plantar nerve was separated from the tendon sheath of the PL by the flexor digitorum longus and flexor hallucis longus tendons in all specimens. CONCLUSIONS: Tendoscopy of the PL at the sole of the foot is described; however, the lateral plantar nerve can be at risk and the tendoscopy should be performed with caution. CLINICAL RELEVANCE: This cadaveric study provides the anatomic basis of the PL tendoscopy of the sole.

The efficacy of molecular subtyping in predicting postoperative recurrence in breast-conserving therapy: a 15-study meta-analysis.

BACKGROUND: Recent research displays that breast cancer (BC) is a heterogeneous disease and distinct molecular subtypes yield different prognostic outcomes. METHODS: We conducted a meta-analysis to clarify the role of molecular subtypes in recurrence risk after breast-conserving therapy (BCT). Eligible studies of single- (ER, PR, Her-2, and p53) and triple-molecular (Luminal A, Luminal B, Her-2, triple-negative) subtypes were identified through multiple search strategies. Pooled hazard ratios with 95% confidence intervals were calculated to assess this research topic. RESULTS: Fifteen studies involving 21,645 participants were included in the meta-analysis. Her-2 positive patients had a significantly higher recurrence risk in both overall merge (HR = 1.97, 95% CI: 1.41-2.75) and subtotal merge of local recurrence (LR) (HR = 1.93, 95% CI: 1.34-2.78). Significantly higher risk of recurrence was also observed in p53 positive patients by overall merge (HR = 1.78, 95% CI: 1.49 -2.12) and subtotal merge of LR (HR = 1.73, 95% CI: 1.44-2.07). When setting Luminal A as a baseline, Luminal B, Her-2, and triple-negative all showed significantly increased risk for both LR and distant recurrence (DR). Comparing triple-negative and non-triple-negative subtypes showed the biggest risk for overall recurrence (HR = 3.19, 95% CI: 1.91-5.31) and LR (HR = 3.31, 95% CI: 1.69-6.45). CONCLUSIONS: Our meta-analysis showed significant differences in recurrence risk among various molecular subtypes after BCT. Although Her-2 and p53 positive subtypes can be considered independent prognostic biomarkers for indicating high LR risk, triple-molecular biomarkers showed higher clinical value. Triple-negative subtype showed the highest recurrence risk among all subtypes, and adjuvant chemotherapy should be considered for it.