[Clinical characteristics and CBS gene analysis of 13 cases with classic homocystinuria].

Objective: To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored. Methods: The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children's Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively. Results: There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. There were 3 patients detected by newborn screening and received treatment at the asymptomatic stage. There were 10 patients clinically diagnosed at the age of 5 to 14 years. Their symptoms appeared at age of 1 to 6 years. The major clinical manifestations were marfanoid features, lens dislocation and (or) myopia, developmental delay, osteoporosis, and cardiovascular diseases. Brain magnetic resonance imaging showed asymmetric infarcts in 4 patients and hypomyelination in 1 case. Increased blood methionine, plasma total homocysteine and urinary total homocysteine with normal urinary methylmalonic acid were found in 13 patients. The biochemical features were consistent with classic homocystinuria. Totally 18 variants were identified in CBS gene of 13 patients, 10 variants were novel and 8 were reported. only 1 patient was partially responsive to vitamin B6 treatment, while 12 cases were non-responsive. They were mainly treated with low methionine diet and betaine supplement. Three vitamin B6 non-responsive cases received liver transplantation at age of 3, 8 and 8 years, respectively. Their blood methionine and total homocysteine returned to normal within a week after liver transplantation. One patient died. Prenatal diagnosis was performed for a fetus when the mother was pregnant again. Two pathogenic CBS gene variants were identified from the amniocytes as same as the proband. Conclusions: The clinical manifestations of classic homocystinuria are complex and variable. Blood amino acid analysis, serum or urine total homocysteine assay and gene analysis are critical for its diagnosis. There were 10 novel CBS gene varients were identified expanding the CBS gene varient spectrum. Liver transplantation is an effective treatment. Prenatal diagnosis is important to prevent classic homocysteinuria.

[Management of complex renal stones by a novel ureterorenoscope with vacuum suctioning system combined with flexible ureteroscope].

Objective: To evaluate the feasibility and safety of Sotn ureterorenoscope combined with flexible ureteroscope on managing complex renal stones. Methods: Patients treated with the Sotn ureterorenoscope combined with flexible ureteroscope between January 2010 and December 2019 were employed from the Sun Yat-sen Memorial Hospital of Sun Yat-sen University and Jiangmen Wuyi Traditional Chinese Medicine Hospital. The patients' information of age, gender, comorbidities, stone characteristics (stone size, hounsfield units, stone composition, stone location, etc.), operative time and console time, stone-free rate (SFR), and perioperative complication rate were collected. The primary outcome was defined as primary SFR in 1 month of operation, and the secondary outcome was the perioperative complication rate. The differences in preoperative and postoperative data between patients with different kinds of stones were compared. Results: A total of 347 patients were included in the study, with 220 males and 127 females. The age [M(Q1,Q3)] was 51 (42, 58) years. There were 94 patients suffered from multiple renal stones and 253 patients with staghorn renal stones. The operative time and console time age [M(Q1,Q3)] for all patients were 87 (55, 115) min and 59 (27, 75) min, respectively. The primary SFR was 81.3% [83.8% for multiple renal stones and 74.5% for staghorn renal stones (P=0.048)]. Complications occurred in 80 patients (23.1%), of which 79 cases were classified as Clavien-Dindo grade 1-2, and 1 case (0.3%) was grade 3-4. For patients with multiple renal stone, compared with the residual stone group, the complete stone-free group had smaller stone size [15.5 (12.0, 21.0) vs 22.0 (17.5, 28.1) mm, P<0.001], and lower hounsfield units [920.0 (658.0, 1 172.5) vs 1 125.0 (944.9, 1 247.5), P=0.022]. Patients with complications had longer operative time than those without complications [60.0 (38.5, 90.0) vs 75.0 (51.3, 110.0) min, P=0.022]. The SFR was higher in patients with stones size ≤ 20 mm compared to those with stones size > 20 mm (91.8% vs 67.5%, P<0.001), while the difference in complication rate was not statistically significant (P>0.05). In the staghorn renal stones group, compared with the residual stone group, the complete stone-free group had smaller stone size [35.0 (25.8, 45.3) vs 53.5 (39.3, 67.5) mm, P<0.001]. Patients with complications had larger stone size than those without complications [43.5 (34.8, 56.5) vs 36.0 (27.0, 50.0) mm, P=0.007]. Patients with stone size ≤ 40 mm had higher SFR (87.5% vs 55.3%, P<0.001) and lower complication rate(10.7% vs 31.6%, P=0.012) compared to those with stone size >40 mm. Conclusion: Sotn ureterorenoscope combined with flexible ureteroscope is an effective and safe choice for the treatment of complex renal calculi.

[Inhibitory effect of DAPT on Notch signaling pathway in curcumin mediated photodynamic therapy for cervical cancer xenografts in nude mice].

Objective: Curcumin was used as photosensitizers in photodynamic therapy on cervical cancer xenografts in nude mice.Analysis the expression changes of Notch and downstream gene as NF-κB and VEGF before and after DAPT inhibition of Notch signaling pathway in vivo experiments.Our aim was to investigate the possible mechanism of Notch signaling pathway in the treatment of cervical cancer with PDT. Methods: A cervical cancer model of nude mice was established by subcutaneous inoculation of human cervical cancer Me180 cells 200 µl.After the success of the model, the experimental animals were divided into 4 groups (model group, curcumin PDT group, simple DAPT group, curcumin-PDT+ DAPT group), each group was 12.Tumor volume changes were analyzed and HE staining was observed in each group.MRNA and protein expression of Notch1 and its downstream NF-κB, VEGF were detected by RT-PCR, immunohistochemistry and Western blot before and after inhibition of Notch signaling pathway by DAPT. Results: Except the control group, the tumor volume of the other three groups remained unchanged or slightly reduced after 1-7 days of treatment.The difference was significant (P<0.05). HE staining showed the most obvious necrosis of curcumin-PDT group with DAPT.Both DAPT and curcumin-PDT could reduce the expression level of Notch1 in mRNA.The inhibition rates were 42.17% and 40.54%, respectively.And the inhibitory effect of curcumin-PDT with DAPT on Notch-1 was the strongest (79.22%) (P<0.01), and two of them had synergistic effect after combination with curcumin-PDT.But the expression of Notch-2 has no obvious inhibitory effect (P>0.05). Both DAPT and curcumin-PDT can inhibit the protein expression of Notch1, NF-κB and VEGF, and two of them have synergistic effect after combined use. Conclusions: DAPT can effectively block the Notch signaling pathway and inhibit the proliferation of cervical cancer cell line Me180.The application of DAPT to inhibit Notch signaling pathway after photodynamic therapy can achieve synergistic effect, which is mainly related to the down-regulation of the expression of Notch1 and NF-κB.Notch signaling pathway may be one of the targets of curcumin-PDT photodynamic therapy.

[A preliminary discussion on the contents and value of Shi er mai (Twelve Channels) and Bie mai (Allo-channels), the medical bamboo slips unearthed from Han tomb in Laoguanshan of Chengdu].

The 52 medical bamboo slips entitled Si er ma (Twelve Channels) and Bie mai (Allo-channels) , unearthed from Han tomb in Laoguanshan, are the exclusive medical books concerning channels. Shi er mai is the first work bearing the term " heart dominating channel" , and the running pathways and manifestations of 12 channels. This book could be the major original sources of the 12-channel theories described in the Chapter of Jing mai (Channels) of Ling shu (Miraculous Pivot) . While Bie mai suggests the coexistence of the multi-channel systems at the time when the book was compiled and, together with the 12 "channel" , and 3 "branched collaterals" , these 2 books represent the original condition before the establishment of the mode of channel circulation in Ling shu, and is significant to explore the nature and origin of channel.

Study on quality standards for Chimonanthus nitens.

Chimonanthus nitens Oliv. is a commonly used traditional Chinese medicine. Terpenoids, flavonoids, and coumarins are usually considered its main bioactive ingredients. Thus, qualitative and quantitative analyses of these compounds are crucial in quality control studies of Chimonanthus nitens. In this study, five compounds were identified by double-development thin layer chromatography (TLC) and the content of four compounds was determined by high performance liquid chromatography; the detection wavelength was set to 344 nm and the column temperature was 40°C. All calibration curves showed good linear regression (R2 > 0.9995). The average recoveries ranged from 97.06 to 104.44%. The RSD was below 4.2%. Four compounds remained stable over 24 h and the relative standard deviation (RSD) of the precision of their measurement was less than 1.5%. The developed method was reproducible, sensitive, and simple, and could be used for quality control of Chimonanthus nitens.

[A preliminary evaluation and discussion on the significance of the medical bamboo slips Ci shu (Needling Methods) unearthed from a Han tomb in the Mount. Laoguan, Chengdu].

The compilation of medical bamboo slips, Ci shu(Needling Methods), which was unearthed from a Han tomb in Mt. Laoguan, is a monograph dealing exclusively with the principles of clinical acupuncture manipulations with 40 acupuncture prescriptions, being the earliest unearthed work with documented standard methods of acupuncture manipulations and acupuncture prescriptions in China. The chapter Zhen fang (Acupuncture Prescriptions) is the earliest summary of standardized acupoint prescriptions up to now in China, which is of great significance to clinical practice directly derived from ancient clinical performance of acupuncture. The chapter Zhen fang of the book Ci shu is also one of the earliest ancient clinical reports archiving the acupoint. This may provide invaluable perspectives to the study of the conceptualization, origination, development, formation of theoretical system, and clinical application of acupoints.

Effect of feeding different sources of rumen-protected methionine on milk production and N-utilization in lactating dairy cows.

Objectives of this study were to quantify production responses of lactating dairy cows to supplying absorbable Met as isopropyl-2-hydroxy-4-(methylthio)-butanoic acid (HMBi), or rumen-protected Met (RPM, Smartamine M; Adisseo, Alpharetta, GA) fed with or without 2-hydroxy-4-(methylthio)-butanoic acid (HMB), and to determine whether Met supplementation will allow the feeding of reduced dietary crude protein (CP). Seventy cows were blocked by parity and days in milk into 14 blocks and randomly assigned within blocks to 1 of the 5 dietary treatments based on alfalfa and corn silages plus high-moisture corn: 1 diet with 15.6% CP and no Met source (negative control); 3 diets with 15.6% CP plus 0.17% HMBi, 0.06% RPM + 0.10% HMB, or 0.06% RPM alone; and 1 diet with 16.8% CP and no Met supplement (positive control). Assuming that 50% of ingested HMBi was absorbed from the gastrointestinal tract and 80% of the Met in RPM was absorbed at intestine, the HMBi and RPM supplements increased metabolizable Met supply by 9 g/d and improved the Lys:Met ratio from 3.6 to 3.0. After a 2-wk covariate period during which all cows received the same diet, cows were fed test diets continuously for 12 wk. Diet did not affect dry matter intake (mean ± SD, 25.0±0.3 kg/d), body weight gain (0.59±0.2 kg/d), or milk yield (41.7±0.6 kg/d). However, feeding HMBi increased yield of energy-corrected milk and milk content of protein and solids-not-fat. Moreover, trends were observed for increased milk fat content and yield of fat and true protein on all 3 diets containing supplemental Met. Apparent N efficiency (milk N/N intake) was highest on the RPM treatment. Feeding 16.8% CP without a Met source elevated milk urea N and urinary excretion of urea N and total N and reduced apparent N efficiency from 34.5 to 30.2%, without improving production. Overall results suggested that feeding HMBi or RPM would give similar improvements in milk production and N utilization.

[Inhibitory effect of yiqijiedu powder to telomerase and telomerase RNA in nasopharyngeal tumorigenesis of rats].

OBJECTIVE: Telomerase activation is a common event in malignant transformation, and is associated with tumorigenesis. This has been clarified in nasopharyngeal carcinoma. YIQIJIEDU powder (Chinese traditional medicine) is used to treated the patients with nasopharyngeal carcinoma (NPC) after radio-therapy and patients with precancerous lesion of NPC. We investigated whether YIQIJIEDU powder inhibits the telomerase activity in nasopharyngeal carcinogenesis. METHODS: Nasopharyngeal carcinomas in rats were induced by N, N' Dinitrosopiperazine (DNP), and some of them were treated with YIQIJIEDU powder. Telomerase and telomerase RNA in the rats' nasopharyngeal tissue were assayed by using PCR-ELISSA and Nested-PCR, and were pathologically diagnosed. RESULTS: YIQIJIEDU powder could inhibit telomerase activity and nasopharyngeal carcinogenesis in the nasopharyngeal tissue of the rats treated, but no telomerase RNA. CONCLUSION: The findings suggest that the anticancer effect of YIQIJIEDU powder links with their inhibitory effects on telomerase.

Paeonilide, a novel anti-PAF-active monoterpenoid-derived metabolite from Paeonia delavayi.

A novel monoterpenoid-derived metabolite, paeonilide, was isolated from the roots of Paeonia delavayi. Its structure was established by a combination of spectroscopic and X-ray crystallographic analyses. It showed an anti-PAF effect with an IC50 value of ca. 8 microg/ml.

[Effect of ligustrazine on kanamycin ototoxicity].

By measuring cochlear superoxide dismutase (SOD) activity, malondialdehyde (MDA) and electrocochleogram (ECoG) in guinea pigs, the antioxidation of Ligustrazine on Kanamycin (KM) was studied. The results showed that SOD activity, MDA content and threshold value of ECoG were significantly increased after KM was administered, while it markedly reduced after Ligustrazine was given. It was considered that lipid hyperoxidative reaction was correlated with KM ototoxicity, Ligustrazine could prevent and treat KM ototoxicity by antioxidation.

[Effects of iodine nutritional status of fetuses, infants and young children on their intelligence development in the areas with iodine-deficiency disorders].

Intelligence in children without iodine supplement during their fetal and infant periods, and in those born three to four years after the implementation of stable supply of iodized salt in the areas with endemic cretinism and goiter was tested with Standord-Binet method. Results indicated there existed a lot of mental retarded children in the iodine-deficiency areas, with most of them born before the implementation of iodine supplement. In order to study the changes of intelligence development in children probably induced by stable supply with iodine, the tested children living in the areas with endemic cretinism were followed-up for two years, and no improvement in children's intelligence could been seen. It suggested that impairment to children's intelligence development caused by iodine deficiency during their fetal and infant periods was irreversible.