[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.

[Sidaxue, a traditional Guizhou Miao herbal medicine formula, reduces necroptosis and synovial vascular proliferation in rats with collagen-induced arthritis by inhibiting the RIPK1/RIPK3/MLKL pathway].

OBJECTIVE: To explore the inhibitory effect of Sidaxue (SX), a traditional Guizhou Miao herbal medicine formula, on necrotic apoptosis and synovial angiogenesis in rats with collagen-induced arthritis (CIA) and the role of the RIPK1/RIPK3/MLKL pathway in mediating this effect. METHODS: Forty-two SD rats were randomized into 6 groups (n=7), including a normal control group, a CIA model group, 3 SX treatment groups at low (10 g/kg), moderate (20 g/kg) and high (40 g/kg) doses, and a GTW treatment group. CIA rat models were established by subcutaneous injections of bovine type II collagen, and the treatments were administered daily by gavage for 21 days. The rats were observed for swelling of the hind limb joints, which was rated using the arthritis index (AI) score on a weekly basis. Serum levels of TNF-α, IL-1ß and IL-17 in the rats were detected using ELISA, and the pathological changes in the synovium were observed with HE staining. Real-time PCR was performed to detect the mRNA expression levels of VEGF, MMP-9, Ang-1, RIPK1, RIPK3, and caspase-8 in the synovial tissues, and the protein expressions of VEGF, MMP9, Ang-1, Stat-3, RIPK1, RIPK3, MLKLl, p-MLKL and caspase-8 were detected using Western blotting. RESULTS: Compared with those in CIA model group, the rats receiving treatment with GTW and SX showed milder swelling of the hind limb joints with significantly lower AI scores (P < 0.05). In CIA model group, a large number of inflammatory cells were observed in the synovium with obvious damages of the tissue structure. In the drug treatment groups, inflammatory cell infiltration, synovial angiogenesis and synovial hyperplasia were alleviated, and the therapeutic effects were obviously enhanced as SX dose increased. Compared with those in the model group, the rats treated with GTW and high-dose SX showed significantly decreased serum levels of IL-1ß, IL-17 and TNF-α (P < 0.05), lower mRNA and protein expressions of RIPK1, RIPK3, VEGF, Ang-1, and MMP9 (P < 0.05), higher expressions of caspase-8 (P < 0.01), and obviously lowered expression of Stat-3 protein and phosphorylation level of MLKL (P < 0.05). CONCLUSION: SX can improve synovial angiogenesis in CIA rats possibly by inhibiting the activation of RIP1/RIP3/MLKL signaling pathway and down-regulating the expression of the vascular growth factors VEGF, Ang-1, MMP9, and Stat-3.

Effects of Chinese herbal medicine and cold exposure on plasma glucose, leucine and energy metabolism in sheep.

An experiment was carried out to assess the feeding effect of Chinese herbal medicine on N balance, ruminal fermentation characteristics, kinetics of plasma glucose, leucine and energy metabolism in sheep kept at thermoneutral environment (23°C) or exposed to cold (2-4°C). Four sheep were subjected to either mixed hay (MH-diet) or hay supplemented with 2% of a traditional nourishing Chinese herbal medicine mixture (Astragalus root, Angelica root and Atractylodes rhizome; CHM-diet) over two 23-day periods using a crossover design. Cold exposure was conducted for 5 days. The isotope dilution of [U-13 C]glucose with open circuit calorimetry was used to determine the turnover and oxidation rates of plasma glucose and metabolic heat production. The rate of plasma leucine turnover was measured with an isotope dilution method using [1-13 C]leucine. N intake was higher, N excretion through faeces was lower and N digestibility was higher for the CHM-diet than the MH-diet. Rumen pH was lower, concentration of rumen NH3 was higher, concentrations of rumen total VFA and acetate tended to be higher and propionate was higher for the CHM-diet compared with the MH-diet. Turnover rate of plasma glucose was higher for the CHM-diet than the MH-diet and increased during cold exposure. Oxidation rate of plasma glucose did not differ between diets and also between environments. Turnover rate of plasma leucine was higher for the CHM-diet compared with the MH-diet but remained similar between environments. Heat production was greater for the CHM-diet than the MH-diet and increased during cold exposure. No significant diet × environment interaction was detected. The present results demonstrated that plasma glucose and energy metabolism were enhanced by both Chinese herbal medicine and cold exposure; plasma leucine metabolism was enhanced by Chinese herbal medicine but with lack of change in response to cold exposure in sheep under the conditions of the current experiment.

Effects of lipid form and source on digestibility of fat and fatty acids in growing pigs.

The objective of this study was to compare the effect of source (corn DDGS, rice bran, or soybean) or form of oil (extracted or intact) on apparent total tract digestibility (ATTD) and true total tract digestibility (TTTD) of acid-hydrolyzed ether extract (AEE) and fatty acids. The study determined and compared the ATTD or TTTD of AEE and fatty acids in extracted corn oil, rice oil, and soybean oil with intact oil in corn DDGS, full-fat rice bran, and full-fat soybean. Seventy-eight barrows (initial BW = 47.2 ± 3.9 kg; Duroc × Landrace × Yorkshire) were allotted to 1 of 13 dietary treatments in a randomized complete block design with 6 barrows in each dietary treatment. The 13 experimental diets included 1 cornstarch-soybean meal basal diet (AEE, 0.56%) and 3 diets containing 6% extracted oils (corn oil, rice oil, and soybean oil) and 9 diets supplemented with 3 levels of corn DDGS (17%, 34%, and 51%), full-fat rice bran (14%, 28%, and 42%), and full-fat soybean (12%, 24%, and 36%). These diets provided about 2%, 4%, and 6% intact oil, respectively. The barrows were housed in individual metabolism crates and were fed the assigned test diets at 4% of initial BW per day. A 5-d total collection of feces followed a 7-d diet adaptation period. The ATTD of AEE were calculated for each diet. The endogenous flow of AEE associated with each ingredient and values for TTTD were calculated using regression methods. The ATTD of AEE were greater ( < 0.05) for extracted oil than for intact oil. Compared to extracted oil, intact oil had lower ( < 0.01) ATTD of palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2), and linolenic acid (C18:3). However, a source by form interaction ( < 0.01) was observed for ATTD of C18:0, C18:2, and C18:3. The ATTD of C18:0, C18:2, and C18:3 in extracted corn and rice oil were greater compared with intact corn DDGS and rice oil ( < 0.05), while there was no significant difference for the ATTD of C18:0, C18:2, and C18:3 between extracted soybean oil and intact oil in full-fat soybean. In conclusion, lipids that are extracted have a greater digestibility compared with intact lipids, and this is especially true regarding saturated fatty acids. The ATTD of AEE in 2 forms of rice oil (intact oil and extracted oil) was less than the values in corn oil and soybean oil. The TTTD of AEE in corn DDGS and full-fat soybeans were greater than in full-fat rice bran.

Application of reversed A2/O process on removing nitrogen and phosphorus from municipal wastewater in China.

The application of reversed A2/O process in practice in China is mainly discussed in this paper. As a new process on nitrogen and phosphorus removal, principle and technical features of reversed A2/O process are also summarized. The application in rebuilt wastewater treatment plant shows that reversed A2/O process not only has merits on high nitrogen and phosphorus removal efficiency, but also has merits on energy saving. The application in newly-build wastewater treatment plant shows that infrastructure and equipment investment of reversed A2/O process economized 15% and 10% respectively, compared to conventional A2/O process. The practical application shows that reversed A2/O process is a new nitrogen and phosphorus removal process, which is suitable for China's national conditions.

Experimentally induced lysosomal dysfunction disrupts processing of hypothalamic releasing factors.

Previous studies have shown that experimentally induced lysosomal dysfunction elicits various features of aging in the cortical telencephalon. The present study used cultured slices to test if: (1) it causes similar changes in the hypothalamus, and/or (2) modifies the processing of two releasing factors important to aging. A 2-day exposure to N-CBZ-L-phenylalanyl-L-alanine-diazomethylketone (ZPAD), a selective inhibitor of cathepsins B and L, triggered a pronounced increase in the numbers of lysosomes in the ventromedial and dorsomedial nuclei, and in lateral hypothalamus. Continued incubation with the inhibitor for 3-12 days resulted in the spread of endosomes-lysosomes into dendrites and, in the lateral hypothalamus, the formation of massive, lysosome-filled expansions of neuronal processes (meganeurites). These effects did not occur in the arcuate nucleus, making it the first region so far examined in which lysosomal proliferation is not initiated by hydrolase inhibitors. Despite this, a dense plexus of axons and terminals in the median eminence was partially depleted of growth hormone releasing hormone (GHRH) within 48 hours after addition of ZPAD. Moreover, the inhibitor caused axonal GHRH to become collected into large puncta, an effect highly suggestive of a partial failure in axonal transport. GHRH mRNA levels were not greatly affected by 6 days of ZPAD exposure, indicating that reduced expression did not play a major role in the peptide changes seen at 48 hours. Similar but less pronounced immunocytochemical changes were recorded for the somatostatin system in the arcuate and periventricular nucleus. It is concluded that lysosome dysfunction: (1) has different consequences for the arcuate nucleus than other brain regions, and (2) disrupts transport of hypothalamic releasing factors. The potential significance of the results to endocrine senescence is discussed.

Risk factors for initiation of drug use among young males in southwest China.

To identify risk factors for drug use among young males in southwest China a cross-sectional survey and a non-concurrent cohort study were conducted. Demographic, behavioral and drug-use information was collected from young males aged 18-29 years. The non-concurrent cohort included the period 1 January 1991 to 1 August 1994. A total of 1548 subjects were interviewed. The cumulative incidence increased between 1991 and 1993. Multivariate analysis identified the following significant risk factors for drug use: being divorced/widowed/separated, having been encouraged by friends/others to try drugs, smoking cigarettes, belonging to the Jingpo ethnic group, and having a family member who used drugs in 1991. More than 6 years of education was a protective factor for drug use. Drug use in the community was associated with having been encouraged by friends or others to try drugs (71%), to smoking cigarettes (50%), and to belonging to the Jingpo group (24%). The results are consistent with community based prevention approaches which should be studied carefully because of the unique cultural and epidemiological situation in China.