[A comparative study between retro-auricular single-site endoscopic thyroidectomy and transoral endoscopic thyroidectomy vestibular approach: a single-center retrospective analysis].

Objectives: To compare the efficiacy of retro-auricular single-site endoscopic thyroidectomy (RASSET) and that of transoral endoscopic thyroidectomy vestibular approach (TOETVA). Methods: In Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 10 patients underwent RASSET from June 2021 to August 2021, and 21 patients underwent TOETVA from January 2016 to August 2021. All the 21 patients' clinical data was analyzed retrospectively. There were 2 males and 8 females in the RASSET group, aging (48.2±13.9) years (range: 28 to 67 years). There were 5 males and 16 females in the TOETVA group, aging (31.3±8.2) years (range: 21 to 49 years). All patients underwent thyroid lobectomy. A 3 cm in length incision was cut on single auricula posterior sulci to creat the approach in the RASSET group. Then a Trocar made with of a glove was inserted. Retaining the omohyoid, the sternocleidomastoid muscle and anterior cervical muscle were pulled apart, exposing a single lobe of the thyroid gland and lymphatic tissue of zone Ⅵ, for en-bloc resection. The clinical data of the two groups were collected and analyzed by t test, Mann-Whitney U test, Fisher exact test or χ2 test. Clinical data and postoperative efficacy indexes such as operation time, postoperative C reactive protein level, and postoperative complications were recorded. Results: Compared with the TOETVA group, the operation time was longer in the RASSET group ((256.8±77.0) minutes vs. (201.2±54.9) minutes, t=2.31, P=0.028), and increase of postoperative C reaction protein (24 hours postoperative vs. preoperative) was lower in the RASSET group (8.58(13.24) mg/L vs. 46.24(48.88) mg/L, Z=-4.311, P<0.01). But there was no significant difference between the RASSET group and TOETVA group in the number of lymph nodes dissection (2(5) vs. 2(3), Z=-0.326, P=0.759). Besides, there were no complications in the RASSET group. Conclusion: Retro-auricular single-site endoscopic thyroid loectomy is easy to achieve the en-bloc resection of tumors with a well-concealed scar and less traumatic dissection.

The Efficacy of Pyrotinib as a Third- or Higher-Line Treatment in HER2-Positive Metastatic Breast Cancer Patients Exposed to Lapatinib Compared to Lapatinib-Naive Patients: A Real-World Study.

Background: Pyrotinib is a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor. Evidence of the efficacy of pyrotinib-based treatments for HER2-positive metastatic breast cancer (MBC) in patients exposed to lapatinib is limited. Methods: Ninety-four patients who received pyrotinib as a third- or higher-line treatment for HER2-positive MBC were included in this retrospective study. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were implemented to balance important patient characteristics between groups. Results: Thirty (31.9%) patients were pretreated with lapatinib and subsequently received pyrotinib as an anti-HER2 treatment, and 64 (68.1%) patients did not receive this treatment. The OS and PFS indicated a beneficial trend in lapatinib-naive group compared to lapatinib-treated group in either the original cohort (PFS: 9.02 vs 6.36 months, p = 0.05; OS: 20.73 vs 14.35 months, p = 0.08) or the PSM (PFS: 9.02 vs 6.08 months, p = 0.07; OS: 19.07 vs 18.00 months, p = 0.61) or IPTW (PFS: 9.90 vs 6.17 months, p = 0.05; OS: 19.53 vs 15.10 months, p = 0.08) cohorts. Subgroup analyses demonstrated lapatinib treatment-related differences in PFS in the premenopausal subgroup and the no prior trastuzumab treatment subgroup, but no significant differences were observed in OS. Conclusion: Pyrotinib-based therapy demonstrated promising effects in HER2-positive MBC patients in a real-world study, especially in lapatinib-naive patients, and also some activity in lapatinib-treated patients.

Genomic Signature of Mismatch Repair Deficiency in Areca Nut-Related Oral Cancer.

Areca nut (AN) chewing contributes to an increase of oral squamous cell carcinoma (OSCC) cases in South and Southeast Asia; however, genomic events underlying the carcinogenesis process of AN-related OSCC remain unclear. Here, we comprehensively describe the genomic and transcriptome alterations of 113 Chinese OSCC patients (89 AN related and 24 AN negative) by whole-exome sequencing and RNA sequencing, and we compared the genomic differences between AN-related and AN-negative samples by integrating sequencing data of 325 OSCC patients from The Cancer Genome Atlas database and 50 from a published Taiwanese study. We identified 11 significantly mutated genes for OSCC, including 4 novel ones (ATG2A, WEE1, DST, and TSC2), of which WEE1 and ATG2A mutated with significantly higher rates in AN-related samples (P = 0.04 and P = 0.003, respectively). Mutational signature analysis revealed that AN-related OSCCs were specially characterized by the genomic signature of mismatch repair deficiency (dMMR), which could also predict the prognosis status of AN-related OSCC. In addition, an elevated PD-L1 expression was also observed in both AN-related patients (P = 3.71 × 10-11) and those with a high dMMR level (P = 1.99 × 10-4). Further differential expression analysis and in vitro experiments confirmed the role of dMMR in the development of OSCC induced by AN exposure. Taken together, this study first revealed the molecular profiles and highlighted the role of dMMR in AN-related OSCC among the Chinese population and identified that AN-related OSCC may represent a potential cohort for effective anti-PD-1/L1 immunotherapy.

Screening of drug metabolizing enzymes for fusidic acid and its interactions with isoform-selective substrates in vitro.

1. Fusidic acid (FA) is widely used for the treatment of infections of sensitive osteomyelitis or skin and soft tissue caused by bacteria. However, the role of cytochrome P450s (CYPs) in the metabolism of FA is unclear. In the present study, we screened the main CYPs for the metabolism of FA and studied its interactions with isoform-selective substrates in vitro. 2. The main CYP450s were screened according to the inhibitory effect of specific inhibitors on the metabolism of FA in human liver microsomes (HLMs) or recombinant CYP isoforms. Enzyme kinetic parameters including Ki, Ki', Vmax, and IC50 were calculated to determine the potential of FA to affect CYP-mediated metabolism of isoform-selective substrates. 3. FA metabolism rate was inhibited by 49.8% and 83.1% under CYP2D6, CYP3A4 selective inhibitors in HLMs. In recombinant experiment, the inhibitory effects on FA metabolism were 83.3% for CYP2D6 and 58.9% for CYP3A4, respectively. FA showed inhibition on CYP2D6 and CYP3A4 with Kis of 13.9 and 38.6 µM, respectively. Other CYP isoforms including CYP1A2, CYP2A6, CYP2C9, CYP2E1, and CYP2C19 showed minimal or no effect on the metabolism of FA. 4. FA was primarily metabolized by CYP2D6 and CYP3A4 and showed a noncompetitive inhibition on CYP2D6 and a mixed competitive inhibition on CYP3A4. Drug-drug interactions between FA and other chemicals, especially with substrates of CYP2D6 and CYP3A4, are phenomena that clinicians need to be aware of and cautious about.

Euglycemic progression: worsening of diabetic retinopathy in poorly controlled type 2 diabetes in minorities.

AIMS: In type 2 diabetes, early effects of strict near-normalization of glucose control on macrovascular and microvascular disease are still uncertain. We evaluated the effects of early dramatic improvement in glycemia on retinal disease in poorly controlled diabetes. METHODS: A retrospective, case-control study in public hospital patients with type 2 diabetes, who had annual retinal imaging as part of a case management program or standard diabetes care. Patients included had ≥2 two retinal images ≥1 one year apart, and at least 3 HbA1C measurements. Retinal images were graded using a modified Scottish Diabetic Retinopathy grading scheme. An 'intensive' group (n=34) with HbA1C decrease >1.5% was compared with randomly chosen patients (n=34) with minimal HbA1C changes. RESULTS: Mean HbA1C (±SEM) over two years was similar in intensive (8.5 ± 0.21%) and control groups (8.1 ± 0.28%, p=NS). However, the intensive group had higher baseline HbA1C and a mean maximal decrease of 4.0 ± 0.41% in contrast to the control group (0.2 ± 0.11%). Retinopathy grade progressed +0.7 ± 0.25 units from baseline in the intensive group (p=0.015), a 22.6% worsening. The control group changed minimally from baseline (0.03 ± 0.14 units, p=NS). Change in retinopathy grade was significantly different between groups (p=0.02). More eyes worsened by ≥ 1 retinal grade (p=0.0025) and developed sight-threatening retinopathy (p=0.003) in the intensive group. Visual acuity was unchanged. CONCLUSIONS: Diabetic retinopathy significantly worsened in poorly controlled type 2 diabetes after early intensification of glycemic control and dramatic HbA1C change. Retinal status should be part of risk-factor evaluation in patients likely to experience marked reductions in HbA1C in poorly controlled diabetes.

Effects of curcumin on the pharmacokinetics of talinolol in human with ABCB1 polymorphism.

This study was to investigate the effect of concomitantly administered curcumin on the pharmacokinetics of talinolol and association with ABCB1 C3435T genetic polymorphism. A two-phase, randomized, single-blind, crossover study was carried out in 18 healthy male volunteers with different genotypes of ABCB1, including C3435C (CC, n = 6), C3435T (CT, n = 6) and T3435T (TT, n = 6). The pharmacokinetics of talinolol were measured after co-administration of placebo or 1000 mg curcumin capsules once daily for 14 days. The AUC(0-48 h) and AUC(0-∞) of talinolol were increased by 67.0% (95% CI: 1.09~2.25; p = 0.002) and 80.8% (95% CI: 0.92~2.69; p = 0.005) respectively with curcumin co-administration. The C(max) of talinolol was significantly higher after curcumin administration as compared with placebo (p = 0.029).The CL/F of talinolol was decreased by 25.9% (p = 0.005) during the curcumin-treated phase. No significant change in t(max) and t(1/2) of talinolol were observed between the placebo- and curcumin-treated phases. AUC(0-48), AUC(0-∞), C(max) of talinolol were extensively increased and CL(oral)/F decreased in TT subjects. Co-administration of curcumin significantly increased the plasma concentration of talinolol in healthy volunteers. The effect of curcumin on talinolol was associated with ABCB1 genotypes (C3435T).

Epilepsy surgery trends in the United States, 1990-2008.

OBJECTIVE: To examine national time trends of resective surgery for the treatment of medically refractory epilepsy before and after Class I evidence demonstrating its efficacy and subsequent practice guidelines recommending early surgical evaluation. METHODS: We performed a population-based cohort study with time trends of patients admitted to US hospitals for medically refractory focal epilepsy between 1990 and 2008 who did or did not undergo lobectomy, as reported in the Nationwide Inpatient Sample. RESULTS: Weighted data revealed 112,026 hospitalizations for medically refractory focal epilepsy and 6,653 resective surgeries (lobectomies and partial lobectomies) from 1990 to 2008. A trend of increasing hospitalizations over time was not accompanied by an increase in surgeries, producing an overall trend of decreasing surgery rates (F = 13.6, p < 0.01). Factors associated with this trend included a decrease in epilepsy hospitalizations at the highest-volume epilepsy centers, and increased hospitalizations to lower-volume hospitals that were found to be less likely to perform surgery. White patients were more likely to have surgery than racial minorities (relative risk [RR], 1.13; 95% confidence interval [CI], 1.10-1.17), and privately insured individuals were more likely to receive lobectomy than those with Medicaid or Medicare (RR, 1.28; 95% CI, 1.25-1.30). CONCLUSION: Despite Class I evidence and subsequent practice guidelines, the utilization of lobectomy has not increased from 1990 to 2008. Surgery continues to be heavily underutilized as a treatment for epilepsy, with significant disparities by race and insurance coverage. Patients who are medically refractory after failing 2 antiepileptic medications should be referred to a comprehensive epilepsy center for surgical evaluation.

Effect of a traditional Chinese medicine Liu Wei Di Huang Wan on the activities of CYP2C19, CYP2D6 and CYP3A4 in healthy volunteers.

Liu Wei Di Huang Wan (LDW), a well-known traditional Chinese medicine, is widely used for the treatment of various diseases in China. This study was designed to investigate the potential herb-drug interactions of LDW in healthy volunteers and attempted to ascertain whether the interaction might be affected by genotypes. We assessed the effect of LDW on the activities of CYP2C19, CYP2D6 and CYP3A4 in 12 Chinese healthy subjects in a single-center, controlled, non-blinded, two-way crossover clinical trial. The subject pool consisted of six extensive metabolizers with CYP2C19*1/*1 and six poor metabolizers with CYP2C19*2/*2. Placebo or 4.8 g LDW (12 pills, 0.2 g/pill, twice daily) was given to each participant for 14 continuous days with a wash-out period of 2 weeks after an oral administration of 30 mg omeprazole, 30 mg dextromethorphan hydrobromide and 7.5 mg midazolam. The activities of CYP2C19, CYP2D6 and CYP3A4 were ascertained by their respective plasma or urinary metabolic ratios on day 14 post-treatment. There is no difference in the activities of the three tested enzymes before or after a 14-day administration of LDW. LDW had no effect on the pharmacokinetic parameters of the substrates and their metabolites. A 14-day administration of LDW did not affect the activities of CYP2C19, CYP2D6 and CYP3A4. LDW is unlikely to cause pharmacokinetic interaction when it is combined with other medications predominantly metabolized by these enzymes.

Hyperammonemic coma in an ornithine transcarbamylase mutation carrier following antepartum corticosteroids.

Women who are carriers of the ornithine transcarbamylase (OTC) mutation are at risk for developing hyperammonemia during the postpartum period and at times of metabolic stress. We present a unique case of hyperammonemic coma occurring in an OTC mutation carrier during the antepartum period. Multiple factors, including the administration of antenatal corticosteroids, likely precipitated this critical condition. Clinicians should be aware of this life-threatening clinical presentation and be prepared to identify, treat, and prevent hyperammonemia in affected individuals.

Clopidogrel inhibits CYP2C19-dependent hydroxylation of omeprazole related to CYP2C19 genetic polymorphisms.

This study explores the impact of clopidogrel on the pharmacokinetics of omeprazole related to CYP2C19 genetic polymorphisms. Twelve healthy volunteers (6 CYP2C19*1/*1, 5 CYP2C19*2/*2, and 1 CYP2C19*2/*3) are enrolled in a 2-phase randomized crossover trial. In each phase, the volunteers are administered a single oral dose of omeprazole 40 mg after pretreatment of either placebo or clopidogrel (300 mg on the first day and then 75 mg once daily for 3 consecutive days). Plasma concentrations of omeprazole and its metabolites are quantified by high-performance liquid chromatography with UV detection. After clopidogrel treatment, the AUC(0-infinity) of omeprazole increases by 30.02% +/- 18.03% (P = .004) and that of 5-hydroxyomeprazole decreases by 24.30% +/- 11.66% (P = .032) in CYP2C19*1/*1. The AUC(0-infinity) ratios of omeprazole to 5-hydroxyomeprazole increase by 74.98% +/- 35.48% (P = .001) and those of omeprazole to omeprazole sulfone do not change significantly (P = .832) in CYP2C19*1/*1. No significant alteration is observed in CYP2C19*2/*2 or *3. Clopidogrel inhibits CYP2C19-dependent hydroxylation of omeprazole in CYP2C19*1/*1 and has no impact on CYP3A4-catalyzed sulfoxidation of omeprazole.

Eight novel MHC class I alleles identified in Chinese-origin rhesus macaques.

We report here the identification of four Mamu-A1 and four Mamu-B novel alleles of Chinese-origin rhesus macaques.

Intravenous dexmedetomidine as an adjunct for labor analgesia and cesarean delivery anesthesia in a parturient with a tethered spinal cord.

For parturients desiring labor analgesia who have contraindications to neuraxial techniques, intravenous opioid-based patient-controlled analgesia (IVPCA) offers a reasonable alternative, although incomplete analgesia and maternal and neonatal respiratory depression can occur. Dexmedetomidine, a highly selective alpha(2) agonist with negligible placental transfer, may be a valuable adjunct to IVPCA by providing additional analgesia without the respiratory depression associated with increasing opioid usage. The successful use of a dexmedetomidine infusion as an adjunct to unsatisfactory fentanyl IVPCA is reported in a 31-year-old parturient with spina bifida occulta and a tethered spinal cord reaching L5-S1. Dexmedetomidine significantly improved the analgesic quality; increased sedation was observed, but the patient was easily rousable to verbal stimuli. No episodes of maternal hypotension or bradycardia, or fetal heart rate irregularities occurred. Cesarean delivery was required for prolonged first stage of labor and presumed chorioamnionitis; it was conducted under general anesthesia during which the dexmedetomidine infusion was continued. A healthy baby boy was delivered with normal Apgar scores and no discernible neurobehavioral or other deficits.

Systematic review: lamivudine prophylaxis for chemotherapy-induced reactivation of chronic hepatitis B virus infection.

BACKGROUND: Reactivation of hepatitis B virus infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented and potentially fatal complication. Data supporting the use of lamivudine for primary prophylaxis have emerged, but its use remains controversial and is not standardized. AIM: To review current randomized-controlled trials, randomized trials and prospective case series to provide a clinically applicable, evidence-based recommendation. METHODS: The published literature was identified using a MEDLINE/PubMed search with secondary review of cited publications, and inclusion of all prospective studies. RESULTS: In nine prospective trials and one randomized-controlled trial, the rate of hepatitis among subjects receiving lamivudine prophylaxis ranged from 0% to 20% (16 of 173, 9.2%), compared with 33-67% among controls. Of patients receiving prophylaxis, 0-24% (15 of 173, 8.7%) developed hepatitis B virus reactivation, compared with 29-56% of controls. Three reactivation-related mortalities were reported (one receiving prophylaxis, two controls). No patients withdrew secondary to toxicity or development of lamivudine-resistant mutations. CONCLUSIONS: The available data show a four- to sevenfold decrease in the rate of hepatitis and hepatitis B virus reactivation in patients who receive lamivudine prophylaxis. It is thus recommended that all hepatitis B surface antigen carriers receive lamivudine, or a comparable anti-viral agent, as prophylaxis from the initiation of chemotherapy until at least 1 year following its completion.

Relaxation and dephasing of multiexcitons in semiconductor quantum dots.

We measure the dephasing time of ground-state excitonic transitions in InGaAs quantum dots under electrical injection in the temperature range from 10 to 70 K. Electrical injection into the barrier region results in a pure dephasing of the excitonic transitions. Once the injected carriers fill the electronic ground state, the biexciton to exciton transition is probed and a correlation of the exciton and biexciton phonon scattering mechanisms is found. Additional filling of the excited states creates multiexcitons that show a fast dephasing due to population relaxation.

Ultralong dephasing time in InGaAs quantum dots.

We measure a dephasing time of several hundred picoseconds at low temperature in the ground-state transition of strongly confined InGaAs quantum dots, using a highly sensitive four-wave mixing technique. Between 7 and 100 K the polarization decay has two distinct components resulting in a non-Lorentzian line shape with a lifetime-limited zero-phonon line and a broadband from elastic exciton-acoustic phonon interactions.

[Analysis of complications and deaths in aged patients with obstructive jaundice].

The reasons of complications and deaths in 98 aged patients with obstructive jaundice were analysed in the paper. Among them, 52 cases were diagnosed as benign obstruction, 46 cases as malignant obstruction; 92 patients were treated by surgical management(15 died), 6 patients were treated without operation(4 died). The results showed that effective management on time and intensive perioperative care are important to minimize the mortality rate. Malignant obstructive jaundice was more harmful to the patients' renal function no the mortality rate would be increased. The operations, internal drainage and pressure reduction of biliary duct, were performed on time, thus the survival rate was improve.

Peripheral tissue distribution of orphanin FQ precusor mRNA in stroke-prone spontaneously hypertensive rats.

The heptadecapeptide orphanin FQ (OFQ) is a recently discovered neuropeptide that exhibits structural features reminiscent of the opioid peptides and that is an endogenous ligant to a G protein-coupled receptor sequentially related to the opioid receptors. OFQ was originally isolated from brain, but the presence of OFQ in peripheral tissues, especially in cardiovascular system, has not been clarified. The present study was designed to investigate the peripheral tissue distribution of OFQ precusor mRNA in stroke-prone spontaneously hypertensive rats (SHRSP) and compare the difference of OFQ precusor mRNA expression in aorta or cultured vascular smooth muscle cells (VSMCs) between SHRSP and wistar-Kyoto normotensive (WKY) rats. By using quantitative reverse transcription-polymerase chain reaction (RT-PCR), OFQ precusor mRNA was detected in aorta and ovary at high levels comparable with the amounts found in brain. Moderate expression was found in testis, while a little OFQ precusor mRNA could be detected in atrium. All other peripheral tissues examined from SHRSP, including ventricle, liver, lung and kidney, showed no expression of OFQ precusor mRNA. In the vascular system, OFQ precusor mRNA was expressed in aorta, pulmonary artery, renal artery and vein at high levels comparable with the amounts found in brain. We also found that OFQ precusor mRNA levels were much higher in aorta or cultured VSMCs from SHRSP than those from WKY rats. In conclusion, the present study has shown that OFQ precusor mRNA is present in some peripheral tissues, especially in cardiovascular and reproductive system, suggesting that OFQ possibly involves in the regulation of cardiovascular and reproductive functions.

Chronic evaluation of orthotopically implanted bileaflet mechanical aortic valves in adult domestic sheep.

This study was intended to develop a technically feasible and reproducible model for chronic hemodynamic and mechanical evaluation of orthotopically implanted bileaflet mechanical aortic valves in adult domestic sheep. Three adult sheep (mean age 22 weeks, mean weight 76 kg) underwent aortic valve replacement using 19-mm bileaflet aortic valves. Standard cardiopulmonary bypass techniques were followed, including mild hemodilution, systemic hypothermia, and cardioplegic arrest. After performing a left fourth intercostal thoracotomy, the valves were placed using interrupted 3-0 Ticron (Davis + Geck) inverted mattress sutures through a transverse aortotomy. The average cardiopulmonary bypass time was 58+/-1 min. No chronic anticoagulation was used. There were no surgical complications. All three animals (100%) remained clinically well until elective sacrifice after postoperative day 150. The average cardiac output for the animals at sacrifice was 3.8+/-1.0 L/min. The mean aortic ejection velocity was 304.7+/-47.3 cm/s and the mean pressure gradient was 24.6+/-6.7 mm Hg. There was no clinically significant thrombus formation or paravalvular leaks. Thus, we have demonstrated that it is technically feasible to orthotopically implant mechanical aortic valves in sheep. There are several features that contribute to the success of this model, including use of a transverse aortotomy, adequate de-airing, and the use of mild hemodilution during bypass. We believe that this model is reproducible and can be used to study other valve designs. In addition, this model allows for site-specific preclinical assessment of new or modified mechanical heart valves.

Long-term evaluation of orthotopically implanted stentless bioprosthetic aortic valves in juvenile sheep.

The aim of this study was to develop a technically feasible and reproducible model for chronic evaluation of stentless bioprosthetic aortic valves implanted orthotopically using juvenile domestic sheep. This report summarizes the results of a study conducted to assess orthotopically placed 19-mm stentless aortic bioprosthetic valves. Twenty-seven juvenile sheep underwent aortic valve replacement. Standard cardiopulmonary bypass techniques were followed. The average cardiopulmonary bypass time was 73 min. No chronic anticoagulation was used. There were two deaths (7%) due to surgical complications. In the remaining 25 experiments, 11 animals (41%) died prior to the scheduled sacrifice on postoperative day 150. One early death occurred due to coccidiomycosis infection, one due to technical error, one due to pulmonary embolus, four due to prosthetic annular size disproportion, and four due to thrombi. The remaining 14 animals (52%) underwent left and right heart catheterization, angiography, echocardiography, and sacrifice after postoperative day 150. The average weight of the sheep at elective sacrifice was 60 kg (mean weight gain 12.5 kg). The average cardiac output for the sacrificed animals was 5.1 L/min. The mean velocity of blood across the aortic valve for the sacrificed animals was 317 cm/s and the mean pressure gradient was 26.2 mm Hg. Two features suggest that this model may have broad application. First, we have demonstrated that it is technically feasible to evaluate orthotopically placed stentless bioprosthetic aortic valves in growing sheep. Second, the aortic root size of the juvenile sheep allows for implantation and evaluation of a human size aortic valve (19 mm). We believe that this model is reproducible and can be used to study stentless valve designs.