[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Surgical strategies and long-term outcomes of total arterial coronary artery bypass grafting: a series of 208 patients].

Objective: To examine the short and long-term clinical outcomes of total arterial coronary artery bypass grafting. Methods: Clinic data of 208 patients with left main and multiple vessel coronary artery disease and undertaken total arterial coronary artery bypass grafting from February 2009 to December 2019 in Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine were analyzed retrospectively. There were 188 males and 20 females with an age of (54.7±10.7) years (range: 32 to 79 years). The harvest of arterial conduits and grafting strategies were depended upon the individual patient characteristics and surgeon's experience. Left internal thoracic artery (LITA) was applied in 207 cases, right internal thoracic artery (RITA) in 38 cases (bilateral internal thoracic artery (BITA) in 37 cases), and radial artery (RA) in 187 cases (188 grafts). The graft number per case was 2.6±0.7 (range: 2 to 4). Surgical procedures was completed with off-pump technique in 98.1% patients (204/208). Subgroup analysis was carried out between subgroup BITA (n=37) and subgroup SITA (single ITA+RA) (n=171). The t test, χ(2) test or Fisher exact test were used to compare the clinic characteristics between the two subgroups. The Kaplan-Meier curve was used to estimate the rate of late mortality, major adverse cardiac cerebrovascular event (MACCE), and target vessel revascularization (TVR). A Cox proportional hazards model was used to identify the independent prognosis factors of late mortality. Results: The overall mortality within 30 days postoperatively was 1.4%(3/208). The incidences of perioperative MACCE, re-operation for bleeding and deep sternal wound infection (DSWI) were 1.9%(4/208), 0.5%(1/208) and 1.4%(3/208), respectively. Perioperative myocardial infarction and TVR were not observed. There was no significant difference of 30-day mortality, MACCE, bleeding and DSWI between subgroup BITA and SITA+RA (all P>0.05). In a follow-up period of (5.4±2.8)years (range: 0.2 to 10.9 years), the incidence of all-cause mortality at 1-, 5- and 10-year was 2.3%, 3.4% and 6.9%, respectively. The incidence of MACCE was 3.9%,11.2% and 28.5%, respectively. The rate of TVR was 0.4%, 3.7% and 11.9%, respectively. Age>65 was an independent prognosis factor of late mortality (HR=1.125, 95% CI:1.050 to 1.205, P<0.01). Conclusions: Total arterial coronary bypass grafting is safe and achievable with proper patient selection and surgical strategies. It significantly decreases the risks of late mortality and repeated revascularization.

[Long-term outcomes of multiple arterial off-pump coronary artery bypass grafting].

Objective: To evaluate the long-term clinical outcomes of multiple arterial off-pump coronary artery bypass grafting (OPCAB) on left main coronary artery or multivessel disease. Methods: A total of 329 patients [303 males and 26 females, with a mean age of (55.1±9.1) years old] with left main coronary artery or multivessel disease who underwent isolated multiple arterial OPCAB in Ruijin Hospital between January 2006 and June 2018 were included. The baseline characteristics, perioperative and long-term outcomes were analyzed. Kaplan-Meier analysis was applied for estimation of freedom from major adverse cardiac and cerebrovascular events (MACCE) and overall survival. Independent predictors of MACCE were assessed by Cox regression analysis. Results: The perioperative mortality was only 0.9% (3/329). The median follow-up time was 65(22, 126) months, and 302 (91.8%) patients were followed up. The long-term MACCE rate, mortality, cardiac mortality, myocardial infarction (MI) rate, stroke rate and target vessel revascularization (TVR) rate were 13.9%, 4.6%, 1.3%, 3.6%, 6.0% and 6.0%, respectively. Among the alive patients, 51.3% were in New York Heart Association (NYHA) Ⅰ class and 80.9% had no recurrence of angina pectoris. The estimated 5-year and 10-year overall survival rates were 97.3% and 93.1%, respectively. The estimated 5-year and 10-year freedom from MACCE survival rates were 91.5% and 78.0%, respectively. Senility (OR=1.058, 95%CI: 1.020-1.097, P=0.002) and history of MI (OR=2.200, 95%CI: 1.131-4.412, P=0.021) were the independent risk factors for late MACCE. Conclusion: Multiple arterial OPCAB appears to be safe and with excellent clinical outcomes in treating left main coronary artery or multivessel disease.

Comparative transcriptome analyses of adzuki bean weevil (Callosobruchus chinensis) response to hypoxia and hypoxia/hypercapnia.

Stored product insects show high adaption to hypoxia and hypercapnia, but the underlying mechanism is still unclear. Herein, a comparative transcriptome on 4th adzuki bean weevil (Callosobruchus chinensis) instar larvae was studied to clarify the response mechanisms to hypoxia (HA) and hypoxia/hypercapnia (HHA) using NextSeq500 RNA-Seq. Transcript profiling showed a significant difference in HA or HHA exposure both quantitatively and qualitatively. Compared with control, 631 and 253 genes were significantly changed in HHA and HA, respectively. Comparing HHA with HA, 1135 differentially expressed genes (DEGs) were identified. The addition of hypercapnia made a complex alteration on the hypoxia response of bean weevil transcriptome, carbohydrate, energy, lipid and amino acid metabolism were the most highly enriched pathways for genes significantly changed. In addition, some biological processes that were not significantly enriched but important were also discussed, such as immune system and signal transduction. Most of the DEGs related to metabolism both in HHA and HA were up-regulated, while the DEGs related to the immune system, stress response or signal transduction were significantly down-regulated or suppressed. This research reveals a comparatively full-scale result in adzuki bean weevil hypoxia and hypoxia/hypercapnia tolerance mechanism at transcription level, which might provide new insights into the genomic research of this species.

[Efficacy of biventricular pacing on preventing heart failure in patients with high degree atrioventricular block (BIVPACE-AVB Trial)].

OBJECTIVE: To investigate the long-term effect of biventricular (BIV) and right ventricular apical (RVA) pacing on cardiac function in patients with high-degree atrioventricular block (AVB) and left ventricular ejection fraction(LVEF)over 35%. METHODS: A total of 118 consecutive patients with high-degree AVB in six hospitals from East China between May 2009 and December 2012 were enrolled in this randomized, double-blind and parallel controlled study. Patients were randomly assigned to BIV and RVA pacing with or without LV lead on after one-week cardiac resynchronization therapy (CRT). Cardiac function including New York Heart Association(NYHA), 6 minute walking distance (6MWD), Minnesota living with heart failure (MLHF) score, LVEF, left ventricular end-diastolic volumes/diameters (LVEDV/LVEDD) and other echocardiography parameters, as well as N-terminal pro-B-type natriuretic peptide (NT-proBNP)were assessed at 6 months and 12 months. RESULTS: A total of 114 patients were successfully implanted with CRT. Cardiac function was significantly improved after one-week BIV pacing (n=57) compared with pre-CRT: rate of patients with NYHA Ⅲ (25.44%(29/114) vs. 9.65%(11/114)), MLHF score (17.1±13.6 vs. 26.9±21.6), 6MWD ((315.4±121.8)m vs. (291.8±102.9)m) and NT-proBNP (157.0(70.0, 639.0) ng/L vs. 444.7(144.0, 1 546.0)ng/L, all P<0.05). In BIV group, 6MWD extended from (314.8±142.7)m to (332.7±117.5)m at 6 months (P<0.05), LVEF increased from (60.7±7.9)% at 1 week to (56.6±10.7)% at 6 months(P<0.05), both LVEDV and LVEDD decreased at 12 months compared with at 1 week ((116.2±39.5)ml vs. (131.4±49.6)ml and (50.2±5.6)mm vs. (52.5±6.8)mm, P<0.05). In RVA group (n=57), 6MWD increased at 6 months compared that at 1week ((342.4±109.9)m vs. (310.2±105.1)m, P<0.05), NT-proBNP was higher at 12 months than that at 1 week (349.5(191.8, 884.3)ng/L vs. 127.0(70.3, 336.7)ng/L, P<0.05). Compared with RVA group, BIV group had a bigger shrink in LVEDV decrease at 12 months was more significant in BIV group ((-16.68±24.30)ml vs. (9.09±29.30)ml, P<0.05). CONCLUSIONS: Cardiac pacing could acutely improve the cardiac function in patients with high-degree AVB and LVEF over 35%. Improvements on cardiac function and remodeling are more significant after 12-month BIV pacing than that of RVA pacing. Clinical Trail Registry: Chinese Clinical Trial Registry, ChiCTR-TRC-10000832.

Relationship of polymorphisms in the cholesteryl ester transport protein gene R451Q with coronary heart disease and diabetes in Uyghur and Han Chinese.

To investigate the relationship of polymorphisms in the cholesteryl ester transport protein (CETP) gene with coronary heart disease (CHD) and diabetes in subjects of Uyghur and Han Chinese origin, 266 subjects with CHD including 154 subjects with type 2 diabetes mellitus and 136 healthy subjects (as a control group) were enrolled in this study. Polymerase chain reaction and an enzymatic assay based on the ligase detection reaction were used to detect R451Q polymorphisms in the CETP gene. The data were used for genotyping to determine the allele frequency distribution of the CETP gene R451Q polymorphism to investigate its effects on lipid and apolipoprotein levels. Genotype and allele frequencies of CETP R451QA did not show any significant differences among the CHD and healthy control groups. Moreover, no significant difference in the CETP R451QA genotype and allele frequency was detected among the subjects of Uyghur and Han origin. Blood levels of lipids and apolipoproteins likewise lacked an association with CETP R451QA genotype frequencies in the CHD/diabetes group. We conclude that the R451Q polymorphisms in the CETP gene had no effects on blood lipid levels and are not a risk factor for CHD in Han and Uyghur Chinese.

Volatile anesthetic isoflurane inhibits LTP induction of hippocampal CA1 neurons through α4ß2 nAChR subtype-mediated mechanisms.

BACKGROUND AND PURPOSE: Volatile anesthetic isoflurane contributes to postoperative cognitive dysfunction and inhibition of long-term potentiation (LTP), a synaptic model of learning and memory, but the mechanisms are uncertain. Central neuronal α4ß2 subtype nicotinic acetylcholine receptors (nAChRs) are involved in the induction of LTP in the hippocampus. Isoflurane inhibits α4ß2 nAChRs at concentrations lower than those used for anesthesia. Therefore, we hypothesized that isoflurane-inhibited LTP induction of hippocampal CA1 neurons via α4ß2 nAChRs subtype inhibition. METHODS: Transverse hippocampal slices (400µm thick) were obtained from male rats (6-8 weeks old). Population spikes were evoked using extracellular electrodes by electrical stimulation of the Schaffer collateral-commissural pathway of rat hippocampal slices. LTP was induced using high frequency stimulation (HFS; 100Hz, 1s). Clinically relevant concentrations (0.125-0.5mM) of isoflurane with or without nicotine (nAChRs agonist), mecamylamine (nAChRs antagonist), 3-[2(S)-2-azetidinylmethoxy] pyridine (A85380) and epibatidine (α4ß2 nAChRs agonist), dihydro ß erythroidine (DHßE) (α4ß2 nAChRs antagonist) were added to the perfusion solution 20min before HFS to test their effects on LTP by HFS respectively. RESULTS: A brief HFS induced stable LTP in rat hippocampal slices, but LTP was significantly inhibited in the presence of isoflurane at concentrations of 0.125-0.5mM. The inhibitive effect of isoflurane on LTP was not only reversible and could be prevented by nAChRs agonist nicotine and α4ß2 nAChRs agonist A85380 and epibatidine, but also mimicked and potentiated by nAChRs antagonist mecamylamine and α4ß2 nAChRs antagonist DHßE. CONCLUSIONS: Inhibition of α4ß2 nAChRs subtype of hippocampus participates in isoflurane-mediated LTP inhibition.

Prevalence of histologic otosclerosis: an unbiased temporal bone study in Caucasians.

BACKGROUND: 'Histologic otosclerosis' refers to a disease process without clinical symptoms or manifestations that can only be discovered by sectioning of the temporal bone at autopsy. 'Clinical otosclerosis' concerns the presence of otosclerosis at a site where it causes conductive hearing loss by interfering with the motion of the stapes or of the round window membrane. Various authors have studied the prevalence of histologic otosclerosis on laboratory collections of temporal bones. Some 12-15% of the temporal bones with histologic otosclerosis have demonstrated stapedial fixation. Using these figures for calculating the prevalence of clinical otosclerosis gives an extrapolated clinical prevalence of 0.99-1.2%. This does not correlate well with the clinical data on otosclerotic families from which a clinical prevalence of 0.3% has been estimated. OBJECTIVE: To study the prevalence of histologic otosclerosis in an unselected series of temporal bones. STUDY DESIGN: During a 1-year period, 118 consecutive pairs of temporal bones of deceased patients at a tertiary center were collected to determine the prevalence of otosclerosis. Although histology remains the gold standard for evaluation of otosclerosis, the gross observation of temporal bone slices combined with microradiography was used to screen for otosclerotic lesions more rapidly and with a lower cost-benefit ratio. The temporal bones with suspected otosclerosis shown with these techniques were further analyzed by conventional histology. RESULTS: 2.5% of the 236 temporal bones (or 3.4% of patients) studied demonstrated histologic otosclerosis. CONCLUSIONS: Although the prevalence of 2.5% is much lower than previously published figures on histologic otosclerosis, the extrapolated data (extrapolated clinical prevalence = 0.30-0.38%) correlate well with clinical studies of otosclerotic families. The previous studies based on laboratory collections were likely biased by the presence of hearing loss or other otological diseases.

Decolorization of C.I. Reactive Yellow 84 in aqueous solution by electrocoagulation enhanced with ozone: influence of operating conditions.

We studied the use of a combination of electrocoagulation (EC) and ozonation for the decolorization of the azo dye, C.I. Reactive Yellow 84 (RY84). The effects of initial dye concentration, initial pH, current density, salt concentration, ozone flow rate, temperature and interelectrode distance on the decolorization of RY84 were investigated. The results showed that a synergistic effect was achieved by combining EC with ozone for the decolorization of RY84. Under the experimental conditions, the decolorization rate increased with an increase in current density. However, the decolorization rate decreased with an increase in initial dye concentration and salt concentration. The interelectrode distance did not substantially affect the decolorization rate. Other operating parameters such as initial pH, ozone flow rate and temperature had both positive and negative effects. Over 97% of the color decay was achieved within 10 min reaction time under reasonable experimental conditions. When the decolorization of RY84 was complete, the efficiency of removal of total organic carbon (TOC) was more than 85%.

Prevalence of otosclerosis in an unselected series of temporal bones.

BACKGROUND: Histologic otosclerosis is a disease process without clinical symptoms or manifestations that can be discovered only by sectioning of the temporal bone at autopsy. Clinical otosclerosis is otosclerosis at a site where it causes conductive hearing loss by interfering with the motion of the stapes or of the round window membrane. Various authors have studied the prevalence of histologic otosclerosis on laboratory collections of temporal bones. Some 12% to 15% of temporal bones with histologic otosclerosis have demonstrated stapedial fixation. Using these figures for calculating the prevalence of clinical otosclerosis gives an extrapolated clinical prevalence of 0.99% to 1.2%. This does not correlate well with the clinical data on otosclerotic families, from which a clinical prevalence of 0.3% has been estimated. OBJECTIVE: To study the prevalence of histologic otosclerosis in an unselected series of temporal bones. STUDY DESIGN: During a 1-year period, 118 consecutive pairs of temporal bones of deceased patients at a tertiary care center were collected to determine the prevalence of otosclerosis. Although histology remains the gold standard for evaluation of otosclerosis, the gross observation of temporal bone slices combined with microradiography was used to screen for otosclerotic lesions more rapidly and with a lower cost/benefit ratio. The temporal bones, which were suspected of having otosclerosis with these techniques, were further analyzed by conventional histology. RESULTS: 2.5% of the 236 temporal bones (or 3.4% of patients) studied demonstrated histologic otosclerosis. CONCLUSIONS: Although the prevalence of 2.5% is much lower than previously published figures on histologic otosclerosis, the extrapolated data (extrapolated clinical prevalence = 0.30% to 0.38%) correlate well with clinical studies of otosclerotic families. The previous studies based on laboratory collections were likely biased by hearing loss or other otologic diseases.

The correlation between the gossypol contents in blood plasma, rete testis fluid, and cauda epididymal fluid following chronic treatment with gossypol in rats.

Concentrations of gossypol in blood plasma, rete testis fluid, and fluid from the caudia epididymidis were measured simultaneously by high performance liquid chromatography in rats treated with gossypol (15 mg/kg daily for 3 weeks). Antispermatogenic effects were demonstrated by loss of sperm motility in the cauda epididymidis and structural changes in the testis. It was found in these treated rats that concentrations of gossypol were lower in rete testis fluid compared with blood plasma but increased significantly in fluid from the cauda epididymidis. The results indicate a restriction of the blood-testis barrier to gossypol and its local concentration in the epididymis after fluid resorption.

Electrolyte composition of rete testis fluid and cauda epididymal plasma and spermatozoa from rats following gossypol treatment.

This investigation was undertaken to study the potassium and sodium concentrations in rete testis fluid and cauda epididymal plasma and spermatozoa following gossypol treatment. Rats were treated orally with gossypol acetic acid at a dose of 15 mg/kg/day for 3 and 6 weeks respectively. There were not abnormal findings in the ionic concentrations of cauda epididymal plasma following 3 or 6-week-treatment. After 6 but not 3 weeks the spermatozoa in the cauda epididymidis were rendered almost completely immotile and malformed with a significant reduction in their potassium concentration and rise in their sodium concentration. No abnormal findings in the morphological picture of the germinal epithelium were observed under such circumstances and fluid and sperm from the rete testis were normal. Therefore, a direct action of gossypol may be exerted locally on the spermatozoa in the epididymis.

Secretion of p-aminohippurate by the rat epididymis.

Secretion of p-aminohippurate (PAH) from blood into the sperm-free lumen of the rat cauda epididymidis was studied by a stop-flow luminal perfusion technique. After an intravenous injection of [3H]PAH, radioactive material with chromatographic properties similar to those of free PAH appeared in perfusates. The highest concentration of PAH reached in the lumen was about 3 times that of the free PAH in blood. This was achieved after equilibration of the epididymis with perfusate for 20 min. Luminal accumulation of PAH by the epididymis was inhibited by intravenous injection of probenecid (32 mg/kg). However, deprivation of androgens by castration for 21 days had no effect on secretion. The rate of secretion (from blood to lumen) of PAH altered in a non-linear fashion with the concentration of free PAH in the blood and showed saturation at a free blood concentration of about 4 mumol/l. The apparent Km and Vmax values were 2 mumol PAH/l blood and 0.2 mumol PAH/h. 20 cm tubule, respectively. Based on the concentration profile of PAH across epididymal cells, a model was proposed for the secretion of PAH. It is concluded that the secretory mechanism is similar to that of the renal tubule. The significance of these results was discussed in relation to the functions of spermatozoa in the male reproductive tract.

Gossypol does not affect testicular fluid secretion in rats.

Male rats fed with gossypol acetic acid at a dose rate of 20 mg/kg/day for 16 weeks were rendered infertile. Spermatozoa flushed out from the cauda epididymides completely lost their capacity to initiate forward motility. However, the rate of testicular fluid secretion measured by the efferent duct ligation technique was not affected by gossypol treatment. The sodium and potassium concentrations of the secreted fluid were found to be unchanged. It is concluded that at low antifertility doses, gossypol disrupts spermatogenic elements in the testis without affecting fluid secretion by the Sertoli cells.