[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.

[Advances in nutritional support therapy for stroke prevention and treatment].

As a serious disease of death and disability, stroke constitutes a serious threat to human health. Because of stroke patients often have high-risk factors of malnutrition such as dysphagia and autonomic eating disorder, the hospitalization time, mortality and disability rate of stroke patients increases. Nutritional therapy can effectively improve the malnutrition of patients, which are of great significance for the treatment and rehabilitation of stroke and the prevention of its complications. Nutrients are important components of nutrition therapy, and different ways of nutrition therapy directly affect the effect of treatment. This article summarizes effects of nutrients and different nutritional treatments on stroke prevention, morbidity and treatment, and provides a theoretical basis and new thinking for further reducing the incidence rate of stroke, improving the quality of life in patients and reducing the financial burden of society and family.

Association between Depressive Symptoms and Supplemental intake of Calcium and Vitamin D in Older Adults.

OBJECTIVES: We explored the associations between depressive symptoms and supplemental calcium and vitamin D intake in older adults. DESIGN: This was a prospective cohort study. PARTICIPANTS: 8,527 older adults aged ≥60 years from Zhejiang Major Public Health Surveillance Program (ZPHS) without depressive symptoms at baseline survey. MEASUREMENTS: Participants were divided into non-supplementation, calcium (Ca), vitamin D, and calcium plus vitamin D (CaD) groups based on their supplemental intake during the past year. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Binary logistic regression analyses were performed to examine the association between depressive symptoms and supplemental intake. RESULTS: When compared to the non-supplementation group, the Ca group exhibited a significant odds ratio (OR) of 0.731 (95% CI: 0.552-0.967, P=0.028). After adjusting for age, sex, and Ca food sources, the OR was even smaller for the CaD group (OR: 0.326; 95% CI: 0.119-0.889, P=0.029). Additionally, our results indicated that taking Ca supplements ≥4 days/week yielded a significant OR of 0.690 (95% CI: 0.492-0.968) after full adjustment. Taking CaD supplements ≥4 days/week yielded a significant OR of 0.282 (95% CI: 0.089-0.898) after adjusting for age, sex, and Ca food sources. CONCLUSIONS: Supplemental intake of Ca or CaD ≥4 days/week can decrease the risk of depressive symptoms in older adults, although CaD supplements may be more effective.

Fermentation Cover Brine Reformulation for Cucumber Processing with Low Salt to Reduce Bloater Defect.

Reformulation of calcium chloride (CaCl2 ) cover brine for cucumber fermentation was explored as a mean to minimize the incidence of bloater defect. This study particularly focused on cover brine supplementation with calcium hydroxide (Ca[OH]2 ), sodium chloride (NaCl), and acids to enhance buffer capacity, inhibit the indigenous carbon dioxide (CO2 )- producing microbiota, and decrease the solubility of the gas. The influence of the cover brine formulations tested, on the cucumber fermentation microbiota, biochemistry, CO2 production, and bloating defect was studied using metagenetics, HPLC analysis, a portable gas analyzer and bloater index, respectively. Cover brine supplementation with Ca(OH)2 and acetic acid resulted in complete fermentations with final pH values 0.5 units higher than the un-supplemented control. Lactic acid production increased by approximately 22%, possibly inducing the observed reduction in the relative abundance of Enterobacteriaceae by 92%. Ca(OH)2 supplementation also resulted in an increased relative abundance of Leuconostocaceae by 7%, which likely contributed to the observed increment in CO2 levels by 25%. A 50% reduction on acetic acid formation was detected when cover brines were supplemented with Ca(OH)2 and 690 mM (4%) NaCl. No significant difference was observed in bloater index as the result of Ca(OH)2 or NaCl supplementation in cover brines, given that the CO2 levels remained at above the 20 mg/100 mL needed to induce the defect. It is concluded that the modified cover brine formulation containing Ca(OH)2 and NaCl enables the complete conversion of sugars, decreases production of CO2 and levels of Enterobacteriaceae, but insignificantly reduces bloater index. PRACTICAL APPLICATION: A cucumber fermentation cover brine containing Ca(OH)2 , 0.26% CaCl2 , 345 mM (2%) NaCl, and acetic acid to pH 4.7 has a functional combination of ingredients enabling a complete conversion of sugars to lactic acid with reduced production of acetic acid and CO2 . It represents a process ready cover brine formulation with the potential to allow the manufacture of cucumber pickles with low salt, enhanced food safety, and reduce environmental impact and water usage. Pilot commercial scale cucumber fermentations brined with such ingredients are to reveal the efficacy of this process ready formulation in the presence of oxygen from air in tanks, as opposed to 3.8 L (1-US gal) closed jars in the laboratory.

[Coenzyme Q(10) treatment for one child with COQ6 gene mutation induced nephrotic syndrome and literature review].

Objective: To summarize the clinical manifestation and molecular characteristics of COQ6 mutation induced nephrotic syndrome, and to evaluate efficacy of CoQ(10) therapy. Method: Clinical data of the case with infantile nephrotic syndrome was summarized, including clinical manifestations, laboratory findings and family investigation. The patient received CoQ(10) 30 mg/(kg·d) therapy. Urine protein/creatinine ratio, serum albumin and creatinine were detected to assess the efficacy of the therapy. Result: (1) The 10 months old boy was presented with nephrotic level proteinuria and hypoalbuminemia. Extra-renal manifestations included cardiovascular abnormality, motor and mental retardation and unilateral ptosis. The patient had no consanguinity. A novel homozygous p. R360W mutation in COQ6 gene was identified and confirmed by next-generation sequencing and Sanger sequencing, respectively. Family analysis showed that homozygous p. R360W mutation in COQ6 gene was inherited from his parents. Missense p. R360W mutation was damaging by prediction online PolyPhen and SIFT software. After 2 months of CoQ(10) complementary therapy, the patient's urine protein/creatinine ratio declined from 7.2 to 1.3, and decreased further to 0.01 mg/mg with normal albumin level and renal function within 3 months. Nephropathy remission was maintained and growth retardation improved significantly during the last follow-up. Nevertheless, the patient manifested with sensorineural deafness at the age of 2 years. (2) There were 6 different mutations in coenzyme Q(10) biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping in the whole world. Each mutation was linked to early-onset SRNS with sensorineural deafness. Renal biopsy revealed FSGS in 7 cases and DMS in 1 case. Other manifestations included ataxia, seizures, facial dysmorphism, nephrolithiasis and growth retardation. Four patients received CoQ(10) supplementation and responded to the treatment. Conclusion: Renal disease caused by recessive COQ6 gene mutation was nephrotic syndrome. The patient benefited from early CoQ(10) complement and reached nephropathy remission.

Cellular expression of retinal dehydrogenase types 1 and 2: effects of vitamin A status on testis mRNA.

We examined expression of retinal dehydrogenase (RALDH) types 1 and 2 in liver and lung, and the effect of vitamin A status on testis expression by in situ hybridization. Liver expressed RALDH1 and RALDH2 only in stellate cells and hepatocytes, respectively. Lung expressed RALDH1 and RALDH2 throughout the epithelia of the airways, from the principal bronchi to the respiratory bronchiole. Vitamin A-sufficient rats expressed RALDH1 in spermatocytes, with less intense expression in spermatogonia and spermatids, and expressed RALDH2 in interstitial cells, spermatogonia, and spermatocytes. Neither Sertoli nor peritubular cells showed detectable RALDH1 or RALDH2 mRNA. Vitamin A deficiency produced a sevenfold increase in RALDH1 and a 70-fold decrease in RALDH2 mRNA in testis. In each case, the net change reflected extensive loss of germ cells, increased intensity of expression in residual germ cells, and expression in Sertoli and peritubular cells. Low-dose RA relatively early during vitamin A depletion supported spermatogenesis and affected expression of both RALDHs, but did not reinstate "vitamin A normal" expression patterns. These results show that: RALDH1 and RALDH2 have distinct mRNA expression patterns in multiple cell types in three vitamin A target tissues; RALDH expression occurs in cell types that express cellular retinol-binding protein and retinol dehydrogenase isozymes (except stellate cells, for which retinol dehydrogenase expression remains unknown); vitamin A deficiency and RA supplementation affects the loci and intensity of RALDH mRNAs in testis; and low-dose RA does not substitute completely for retinol. Overall, these data provide insight into the unique functions of RALDH1 and RALDH2 in retinoid metabolism.

[Pharmacognostical identification of antelope horn(Cornu Saigae Tataricae) and its adulterants].

OBJECTIVE: To provide appropriate information and scientific basis for identifying antelope horn (Saiga tatarica) contained in traditional Chinese patent medicines, and formulate relevant quality criteria through experiments. METHOD: Conducting comparative identification of macroscopic and microscopic characteristics of antelope horn(Saige tatarica) and its adulterants (Procapra gutturosa, Pantholops hodgsoni, Ovis ammon and Capra hircus) and giving a comparative table and an indented key to the main characteristics. RESULT AND CONCLUSION: There are remarkable differences between the authentic product and adulterants in both macroscopic and microscopic characteristics.

[Identification of powdered Bungarus multieinctus Blyth and its adulterants].

This paper reports the results of identification of powdered Bungarus muliteinctus and its adulterants (Natrix annularis; Dinodon rufozonatum and Bungarus fascitus). A comparative table of and a key to the characteristics are given.

Coexpression of the mRNAs encoding retinol dehydrogenase isozymes and cellular retinol-binding protein.

We used in situ hybridization of adult rat tissue to show that mRNAs encoding cellular retinol-binding protein (CRBP) and retinol dehydrogenase (RoDH) isozymes I/III and II were expressed in hepatocytes uniformly throughout the liver lobule, but were absent from Kupffer cells and endothelial cells of blood vessels and bile ducts. In kidney, CRBP, RoDH(I), and RoDH(II) were found in the proximal tubules of the cortex. Distal tubules, Henle's loops, collecting ducts, and glomeruli showed little, if any, expression. In testis, CRBP, RoDH(I), and RoDH(II) were found in Sertoli cells. Expression, albeit weaker, also occurred in spermatogonia and primary spermatocytes. Peritubular cells and other germ cells had even weaker expression. Only CRBP and RoDH(II) mRNA were detected in interstitial cells. In lung CRBP, RoDH(I) and RoDH(II) were expressed most intensely in the epithelium of the bronchi and bronchioli, but also occurred in the simple columnar epithelial cells of the alveolar duct and in alveolar type II cells. These data are consistent with the hypothesis that holo-CRBP serves as substrate for retinoic acid biosynthesis because they show that the substrate and the enzyme occur in the same cellular loci in vivo. These data also indicate that multiple cellular sites of retinoic acid biosynthesis occur throughout tissues. Also, the general concordance between mRNA localization and CRBP expression patterns, revealed by previous immunocytochemistry studies, supports and extends the conclusion that CRBP mRNA expression correlates with CRBP expression, based earlier on comparing RNA assays with radioimmunoassays.

Selective up-regulation of alpha1a-adrenergic receptor protein and mRNA in brown adipose tissue by neural and beta3-adrenergic stimulation.

Previous studies have shown that neural stimulation of brown adipose tissue (BAT) reorganizes the expression and activity of signaling proteins in the beta-adrenergic adenylyl cyclase pathway. Cold stress increases neural stimulation of BAT and increases alpha1-adrenergic receptor number; however, the alpha1 receptor subtype involved and the mechanism of up-regulation by cold stress have not been determined. Using reverse transcription/polymerase chain reaction analysis and nuclease protection assay, BAT was demonstrated to express mRNAs encoding alpha1a and alpha1d, but not alpha1b, receptors. Parallel pharmacologic studies of BAT membranes and recombinant alpha1a and alpha1d receptors expressed in COS-7 cells demonstrated that alpha1a receptors predominate in BAT. Exposure of rats to 4 degrees for 4 days increased alpha1a receptors and mRNA in BAT but did not alter expression of alpha1d receptors or mRNA. The induction of alpha1a receptor and mRNA level by cold stress was prevented by selective surgical denervation of BAT. Furthermore, alpha1a receptor and mRNA expression could be induced in warm-adapted rats by infusions of the selective beta3-adrenergic receptor agonist CL 316,243. These data indicate that neural activation of beta3-adrenergic receptors is an important determinant of alpha1a adrenergic receptor expression in BAT.

[Quality criteria for bazhen shennongyin liquor].

Radix Angelicae Sinensis, Radix Paeoniae Alba and Radix et Rhizoma Rhei in Bazhen Shengnongyin Liquor were identified by TLC. The contents of ginsenoside Rb1 in the preparation was determined by TLCS. Simple, accurate and reproducible, this method could be used as the quality criteria for this preparation.

cDNA cloning and characterization of a cis-retinol/3alpha-hydroxysterol short-chain dehydrogenase.

We report a mouse cDNA that encodes a 317-amino acid short-chain dehydrogenase which recognizes as substrates 9-cis-retinol, 11-cis-retinol, 5alpha-androstan-3alpha,17beta-diol, and 5alpha-androstan-3alpha-ol-17-one. This cis-retinol/androgen dehydrogenase (CRAD) shares closest amino acid similarity with mouse retinol dehydrogenase isozymes types 1 and 2 (86 and 91%, respectively). Recombinant CRAD uses NAD+ as its preferred cofactor and exhibits cooperative kinetics for cis-retinoids, but Michaelis-Menten kinetics for 3alpha-hydroxysterols. Unlike recombinant retinol dehydrogenase isozymes, recombinant CRAD was inhibited by 4-methylpyrazole, was not stimulated by ethanol, and did not require phosphatidylcholine for optimal activity. CRAD mRNA was expressed intensely in kidney and liver, in contrast to retinol dehydrogenase isozymes, which show strong mRNA expression only in liver. CRAD mRNA expression was widespread (relative abundance): kidney (100) > liver (92) > small intestine (9) = heart (9) > retinal pigment epithelium and sclera (4.5) > brain (2) > retina and vitreous (1.6) > spleen (0.7) > testis (0.6) > lung (0.4). CRAD may catalyze the first step in an enzymatic pathway from 9-cis-retinol to generate the retinoid X receptor ligand 9-cis-retinoic acid and/or may regenerate dihydrotestosterone from its catabolite 5alpha-androstan-3alpha,17beta-diol. These data also illustrate the multifunctional nature of short-chain dehydrogenases and provide a potential mechanism for androgen-retinoid interactions.

Cloning of a rat cDNA encoding retinol dehydrogenase isozyme type III.

The primary and rate-limiting step in retinoic acid (RA) biosynthesis requires the conversion of retinol into retinal. Previously, two genes encoding retinol dehydrogenases (RoDH), which recognize holo-cellular retinol-binding protein as substrate, had been cloned, expressed and identified as members of the short-chain dehydrogenase/reductase (SDR) gene family. This work reports the cloning of a cDNA encoding a third RoDH isozyme, RoDH(III). The deduced amino-acid sequence of RoDH(III) indicates 97.8% identity with RoDH(I) and 82.3% identity with RoDH(II). RNase protection assays revealed RoDH(III) mRNA expression only in rat liver, in contrast to RoDH(I) and RoDH(II), which had their mRNA expressed in rat liver, kidney, lung, testis and brain. These data extend the insight that a subfamily of SDR isozymes, tissue-distinctively expressed, catalyzes the first step in RA biogenesis.

Cloning of a cDNA for a second retinol dehydrogenase type II. Expression of its mRNA relative to type I.

A retinol dehydrogenase, RoDH(1), which recognizes holo-cellular retinol-binding protein (CRBP) as substrate, has been cloned, expressed, and identified as a short-chain dehydrogenase/reductase (Chai, X., Boerman, M. H. E. M., Zhai, Y., and Napoli, J. L. (1995) J. Biol. Chem. 270, 3900-3904). This work reports the cloning and expression of a cDNA encoding a RoDH isozyme, RoDH(II). The predicted amino acid sequence verifies RoDH(II) as a short-chain dehydrogenase/reductase, 82% identical with RoDH(I). RoDH(II) recognized the physiological form of retinol as substrate, CRBP, with a Km of 2 mM. Similar to microsomal RoDH and RoDH(I), RoDH(II) had higher activity with NADP rather than NAD, was stimulated by ethanol and phosphatidyl choline, was not inhibited by the medium-chain alcohol dehydrogenase inhibitor 4-methylpyrazole, but was inhibited by phenylarsine oxide and the short-chain dehydrogenase/reductase inhibitor carbenoxolone. Northern blot analysis detected RoDH(I) and RoDH(II) mRNA only in rat liver, but RNase protection assays revealed RoDH(I) and RoHD(II) mRNA in kidney, lung, testis, and brain. These data indicate that short-chain dehydrogenases/reductase isozymes expressed tissue-distinctively catalyze the first step of retinoic acid biogenesis from the physiologically most abundant substrate, CRBP.

Cloning of a cDNA for liver microsomal retinol dehydrogenase. A tissue-specific, short-chain alcohol dehydrogenase.

Retinoic acid, a hormone biosynthesized from retinol, controls numerous biological systems by regulating eukaryotic gene expression from conception through death. This work reports the cloning and expression of a liver cDNA encoding a microsomal retinol dehydrogenase (RoDH), which catalyzes the primary and rate-limiting step in retinoic acid synthesis. The predicted amino acid sequence and biochemical data obtained from the recombinant enzyme verify it as a short-chain alcohol dehydrogenase. Like microsomal RoDH, the recombinant enzyme recognized as substrate retinol bound to cellular retinol-binding protein, had higher activity with NADP rather than NAD, was stimulated by ethanol or phosphatidylcholine, was not inhibited by 4-methylpyrazole, was inhibited by phenylarsine oxide and carbenoxolone and localized to microsomes. RoDH recognized the physiological form of retinol, holocellular retinol-binding protein, with a Km of 0.9 microM, a value lower than the approximately 5 microM concentration of holocellular retinol binding protein in liver. Northern and Western blot analyses revealed RoDH expression only in rat liver, despite enzymatic activity in liver, brain, kidney, lung, and testes. These data suggest that tissue-specific isozyme(s) of short chain alcohol dehydrogenases catalyze the first step in retinoic acid biogenesis and further strengthen the evidence that the "cassette" of retinol bound to cellular retinol-binding protein serves as a physiological substrate.

[Determination of esculetin in semen Euphorbiae lathyridis L. by TLCS and comparison on the quality in different areas].

A TLC-densitometric method for the determination of oesculetin in Semen Euphorbia lathyridis (Euphorbiae lathyrdis) was established, and esculetin content in Semen Euphorbia lathyridis from three different producing areas (Zhengzhou, Chengdu and Chongqing) was determined. The method is accurate, sensitive and simple. The recovery is 98.63% and the coefficient of variation is 1.59% (n = 5). The esculetin average contents in the three samples are 0.3013%, 0.2046% and 0.2094% respectively.

TCM treatment of male infertility due to seminal abnormality--a clinical observation of 82 cases.

82 male patients of infertility due to seminal abnormality were treated by Ju Jing Powder with a total effective rate of 85.4%. The sperm density in seminal fluid, the total sperm number in a single ejaculation and the activity rate of sperms markedly improved as compared with those before treatment (P less than 0.01), especially the grading of sperm motility.