Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Electromyographic signals and the starting threshold voltage of orbicularis oris muscle in healthy rhesus monkeys / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of electromyography (EMG) signals and the starting threshold voltages of the orbicularis oris muscles (OOM) in healthy rhesus monkeys under different muscle movement conditions. Methods: The EMG signals and the starting threshold voltages at different time points in 4 healthy rhesus monkeys were acquired and recorded with EMG device and evoked potentiometer. The voltage amplitude variation of EMG signals was analyzed, and the voltage amplitude range of EMG signals at the beginning of OOM contraction was established. The data were statistically analyzed by one-way ANOVA. Results: The EMG of OOM in healthy monkeys in the quiet, natural and continuous mouth-closed state was linear and relatively stable, and the absolute value fluctuated between 15 and 50 μV. The EMG waveform increased rapidly during the natural lip contraction movement, and its amplitude fluctuated greatly, with the highest absolute value of the peak value reaching hundreds of microvolts. The amplitude of EMG induced by continuous mouth closure was more than thousands of microvolts. There was no significant difference in EMG amplitudes of OOM in the healthy rhesus monkey under quiet and continuous lip closure at different time points (P>0.05). There was no significant difference in threshold voltages in the state of natural lip contraction of bilateral OOM at different time points (average range: 57.17-57.47 μV) in the healthy rhesus monkeys (P>0.05). There was no significant difference in threshold voltages of OOM induced by bilateral OOM at different time points(average range: 55.38-55.99 μV) in the healthy rhesus monkeys(P>0.05). There were significant differences in the absolute values of EMG amplitudes of OOM between the three lip movement modes: (30.67±8.72) μV in quiet and natural continuous lip closure (475.12±54.72) μV in natural lip contraction, and (921.22±312.79) μV in the induced persistent lip closure, with t values of -8.48, -9.35 and -5.01 respectively, all P<0.001. Conclusions: The EMG signals of OOM show different characteristics under different muscle movement conditions, which can be used as a basis for computer to judge and recognize the movement conditions of OOM. The upper limits of the EMG threshold voltage values of OOM under different motion states are 55-60 μV.

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial.

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.

Toxic effect of neonatal exposure to 2,2',4,4',5,5'-hexa-chlorobiphenyl on spermatogenesis in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To determine the long-term testicular effect after neonatal exposure to 2,2', 4,4',5,5'-hexa-chlorobiphenyl (PCB153).</p><p><b>METHODS</b>On birth day (Postnatal day 0, PNDO), the Sprague-Dawley (SD) male rats were mixed together and divided into 12 pups/litter. At PND1, the rats were grouped randomly into control and treatment groups according to different litters, 24 pups/group. They were treated by oral gavage with PCB153 in corn oil at doses of 0, 0.025, 0.250 and 2.500 mg/kg BW-day from PNDI to PND7. The rats were sacrificed at PND8 and PND90 by anesthesia. The testes were collected and weighed for histological examination and daily sperm production at PND8 or/and PND90. The epididymidis and the epididymidis cauda also were collected and weighed for determination the sperm counts at PND90.</p><p><b>RESULTS</b>The body weight of 2.500 mg/kg dose group was decreased significantly from PND3 to PND8 compared with that of control (P < 0.05). At PND8, the loose structure in seminiferous cord and the spermatogonia with enlarged volume and detached from the cord were observed in 2.500 mg/kg dose group by light microscope and electronic microscopy. With the increase of exposure doses, the testicular daily sperm production (DSP) and the sperm counts of epididymidis cauda were decreased in dose-dependent manner at PND90. The DSP in 0.250 mg/kg [30 x 10(6)/testis(g)] and 2.500 mg/kg [18 x l0(6)/testis(g)] dose groups were significantly reduced compared with that of control [36 x 10(6)/testis(g)] (P < 0.05). And there was a significant reduction in the sperm counts of epididymidis cauda in 0.250 mg/kg [42 x 10(7)/epididymidis cauda (g)] and 2.500 mg/kg [18 x 10(7)/epididymidis cauda (g)] dose groups compared with that of control [51 x 10(7)/epididymidis cauda (g)] (P < 0.05).</p><p><b>CONCLUSIONS</b>The spermatogenesis of adult testis is disturbed, which causes the decrease in the testicular DSP and the sperm counts of epididymidis cauda after neonatal exposure to PCB153. The long-term damage in male reproductive function is caused by neonatal exposure to chemicals.</p>

Research on the electromyographic signals of orbicularis oculi muscle of rabbit / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the features of electromyographic signals of orbicularis oculi muscle (OOM) of normal rabbits in various movement states, and to clarify relationships between functional actions of OOM and their electromyographic signals, hoping to obtain information concerning the electromyographic signals controlling OOM as reference for restoring the eye-closing function by artificial facial nerve prosthesis in patients with unilateral peripheral facial palsy.</p><p><b>METHODS</b>The electromyographic signals were extracted from OOM of normal rabbits by implanted microelectrodes through upper and lower eyelids. Then the features of these electromyographic signals were analyzed in the time domain and the frequency domain.</p><p><b>RESULTS</b>The peak values of the absolute electromyographic amplitude for natural continuous eye-opening event, natural continuous eye-closing state, natural eye-blinking movement and evoked eye-closing state were (28.8 ± 4.8) µV, (36.0 ± 4.7) µV, (398.8 ± 195.7) µV, and (715.4 ± 249.7) µV, respectively. The peak frequency values of the power spectrum density (PSD) of electromyographic signals for the four modes were (98 ± 17) Hz, (142 ± 22) Hz, (203 ± 58) Hz, and (349 ± 81) Hz, respectively. The electrical activities during the natural continuous eye-opening event and the natural continuous eye-closing state were stable and displayed low amplitudes. During the spontaneous blink state and the evoked eye-closing state, the electromyographic amplitudes markedly increased, and the increased level in the latter state was stronger than that in the former state. When rabbits continuously closed eyes or opened eyes, all of the peak values of the absolute voltage amplitudes were less than 50 µV. The absolute amplitude values of the starting site were between 50 µV and 60 µV during the spontaneous blink and the evoked eye-closing movements. The whole frequency band of the energy of PSD about OOM was between 0 Hz and 500 Hz, and the focus frequency range was between 20 Hz and 350 Hz.In the time domain, the difference was not significant for the electromyographic signals of OOM between the continuous eye-opening state and the continuous eye-closing movement (P > 0.05), but there were statistically significant differences in the other states for their pairwise comparisons (P < 0.05). In the frequency domain, there was no statistically significant difference for the peak frequency of PSD about the electromyographic signals when comparing the continuous eye-opening state with the continuous eye-closing event (P > 0.05). When comparing this item in the other movements with each other, however, the differences were statistically significant (P < 0.05).</p><p><b>CONCLUSIONS</b>OOM relaxes when eyelid keeps continuously opening. The action of eyelid-closing is due to contraction of this muscle. Each state has its own features of the electromyographic signals for OOM, these features can be used as criteria for computers to judge and identify various movement states of OOM. However, it is difficult to distinguish the natural continuous eye-opening event from the natural continuous eye-closing state, based on the features of electromyographic signals in the time and frequency domain.</p>

Effect of neonatal exposure to environmental pollutants on the DNA methylation of rat testis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of neonatal exposure of DNA methylation inhibitor, Cadmium and PCB153 on DNA methylation, apoptosis and spermatogenesis in SD rats.</p><p><b>METHODS</b>Neonatal SD rats were randomly divided into 10 groups and received oral administrations of PCB153 (0.025, 0. 250, 2.500 mg/kg), or Cadmium (1, 2, 4 mg/kg), or positive control 5-Aza-CdR (0.025, 0.250 mg/kg), or vehicle control for five days from PND3. Half of the rats were killed 24 h after the last administration. The remains were fed until 12 weeks. Sperm numbers, apoptosis and DNA methylation levels in testis were investigated.</p><p><b>RESULTS</b>The daily sperm production was significantly decreased in each neonatal exposed group (P < 0.05). Neonatal rats exposed to 5-Aza-CdR and Cadmium reduced the global DNA methylation level, increased apoptosis, while PCB153 exposure did not significantly change DNA methylation and apoptosis.</p><p><b>CONCLUSION</b>Neonatal rats exposed to chemicals could reduce spermatogenesis via multiple pathways. Lower DNA methylation and increased neonatal apoptosis were suggested as one of the causes.</p>

Mandibular swing procedure for surgical resection of advanced oropharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore a better approach to resect the advanced oropharyngeal carcinoma.</p><p><b>METHODS</b>From 1995 to 2005, 17 patients underwent mandibular swing procedure for excision of advanced oropharyngeal carcinoma including: 13 tonsillar cancers, 2 soft palate carcinomas and 2 lingual root cancers. Surgical procedure was selected according to the lesion. All tumors were resected through the mandibular swing approach or its combined approaches. Immediate reconstruction of the surgical defect was done using tongue flap, pectoralis major myocutaneous flap, sternohyoid myofascial flap, temporalis myofascial flap and forehead flap, respectively. After surgical resection of the tumors, all patients received postoperative radiotherapy.</p><p><b>RESULTS</b>All patients' advanced oropharyngeal carcinoma were successfully resected as planned through the mandibular swing procedure or its combined procedures without severe complications. Functions of deglutition, respiration and speech were well restored. The 3- and 5-year survival rate was 54. 5% and 40%, respectively.</p><p><b>CONCLUSION</b>The mandibular swing procedure and its combined approach is safe and effective in the surgical resection of the advanced oropharyngeal carcinoma, which can provide a good exposure for the oropharynx, supraglottic region, hypopharynx, the parapharyngeal space and the base of the skull.</p>

GABAergic neurons innervating the preganglionic cardiac vagal neurons in the dorsal motor nucleus receive tonic glutamatergic control / 生理学报

The glutamatergic innervations and the GABAergic innervations are respectively the major excitatory and inhibitory inputs of preganglionic cardiac vagal neurons (CVNs). Whether and how these two kinds of innervations interact in the regulation of CVNs is unknown. Using retrograde fluorescent labeling of CVNs and voltage patch-clamp technique, we demonstrated that mixed global application of glutamatergic NMDA and non-NMDA antagonists AP(5) and CNQX, while had no effect on the GABAergic synaptic events of the CVNs in the nucleus ambiguus (NA), significantly decreased the GABAergic synaptic events of the CVNs in the dorsal motor nucleus of the vagus (DMNX). These results suggest that the GABAergic neurons preceding the CVNs in the DMNX receive tonic glutamatergic control, whereas the GABAergic neurons preceding the CVNs in the NA receive little, if any, glutamatergic innervations. This differential central regulation of the CVNs in the DMNX from those in the NA might be a possible mechanism that enables the CVNs in the DMNX play different roles from those in the NA in the parasympathetic control of heart rate and cardiac functions.

Clinical observation on treatment of chronic suppurative otitis media caused large tympanic membranes perforation by ear-dropping with combined Chinese and Western drugs / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effect of the self-prepared ear dropping made by combined Chinese and Western drugs in treating chronic suppurative otitis media caused large tympanic membrane perforation.</p><p><b>METHODS</b>Sixty-four patients were randomly divided into two groups, the treated group treated with the self-prepared ear-dropping and the control group treated with ear-dropping made by placebo, to observe the therapeutic effect and adverse reaction.</p><p><b>RESULTS</b>In the 32 patients of the treated group, 15 patients were cured, the cured tympanic membrane was normal in shape and thickness in 11, scarred in 3, and thin and transparent in 1. The hearing was improved in all patients with cured tympanic membrane. But no one was cured in the control group.</p><p><b>CONCLUSION</b>The self-prepared ear-dropping had good effect in treating tympanic membrane perforation, it is simple, cheap and no need of further operation.</p>