[Explore the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab in patients with ulcerative colitis].

Objectives: To analyze the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab (VDZ) in patients with ulcerative colitis (UC). Methods: Retrospective study. By retrieving the clinical database of the Second Affiliated Hospital of Wenzhou Medical University, the patients with moderately to severely active UC were collected, who underwent VDZ treatment from January 2020 to June 2022. The modified Mayo score and Mayo endoscopic score (MES) were employed to evaluate disease activity and intestinal inflammation in UC patients, respectively. According to whether vitamin D was supplemented during VDZ treatment, the patients were divided into supplementary group and non-supplementary group. According to baseline serum 25(OH) D level, UC patients were divided into vitamin D deficiency group and non-deficiency group. According to whether vitamin D was supplemented, the patients of each group were divided into supplementary subgroup and non-supplementary subgroup, respectively. The clinical response rate, clinical remission rate and mucosal healing rate at week 30 after receiving VDZ treatment and the retention rate of VDZ at the 72nd week were observed. The effect of baseline serum 25 (OH) D level on the efficacy of vitamin D supplementation was analyzed by chi-square test. The effects of vitamin D supplementation on the clinical efficacy and drug retention of VDZ in UC were analyzed by chi-square test and Kaplan-Meier curve, respectively. Results: A total of 80 patients with moderately to severely active UC, who were aged (39.4±13.0) years(18-75 years), 37 male and 43 female, were included. There were 43 cases in supplementary group and 37 cases in non-supplementary group. There were 59 cases in the deficiency group, including 32 cases in the supplementary subgroup and 27 cases in the non-supplementary subgroup. There were 21 cases in the non-deficiency group, including 11 cases in the supplementary subgroup and 10 cases in the non-supplementary subgroup. At week 30, the average level of serum 25(OH) D was shown to be higher in supplementary group than that at week 0 [(24.5±5.4) vs (17.7±6.7) µg/L, P<0.001]. At week 30, in contrast with non-supplementary group, erythrocyte sedimentation rate(ESR)[75.0% (24.3%, 86.7%) vs 32.7% (-2.6%, 59.3%), P=0.005] and modified Mayo score [(4.7±2.8) vs (2.3±2.7) points, P<0.001] and MES score [(1.2±1.1) vs (0.4±0.9) points, P=0.001] were significantly reduced, clinical response rate [79.1%(34/43) vs 56.8%(21/37), P=0.032], clinical remission rate [67.4%(29/43) vs 29.7%(11/37), P=0.001] and mucosal healing rate [72.1%(31/43) vs 37.8%(14/37), P=0.002] were higher. At week 72, drug retention rate of VDZ was shown to be higher in supplementary group than in non-supplementary group [55.8%(24/43) vs 27.0%(10/37), P=0.004]. The further analysis showed that vitamin D supplementation could only improve clinical response rate[71.9%(23/32) vs 44.4%(12/27), P=0.033], clinical remission rate[62.5%(20/32) vs 14.8%(4/27), P<0.001], mucosal healing rate[68.8%(22/32) vs 22.2%(6/27), P<0.001] and drug retention rate [53.1%(17/32) vs 13.8%(4/27), P=0.001] in the patients with vitamin D deficiency. Conclusion: Vitamin D supplementation contributes to improving clinical response rate, clinical remission rate, mucosal healing rate and drug retention rate of VDZ in UC patients.

[Transmission chains of local epidemic of COVID-19 caused by 2019-nCoV Delta variant in Zhenhai district, Ningbo].

Objective: To investigate the local epidemic of COVID-19 caused by 2019-nCoV Delta variant in Zhenhai district of Ningbo, identify the transmission chain and provide reference for the prevention and control of COVID-19 epidemic. Methods: The incidence data of COVID-19 in Zhenhai from 6 to 18 December, 2021 were collected in field investigation. Field epidemiological investigation was conducted to understand the epidemiological characteristics of COVID-19 cases and analyze the transmission chains. Results: The first case might be infected with 2019-nCoV through direct or indirect exposure when passing through a medium-risk area, then a family cluster was caused, and the epidemic spread through close contacts of family members with others such as work, daily life, and moxibustion. The epidemic lasted for 14 days, and 74 confirmed COVID-19 cases were reported. The median incubation period was 4.0(3.0,5.8)d. All the cases were in a chain of transmission for more than 6 generations, and the intergenerational interval was 3.5(2.0,5.3)d. The gene sequencing result indicated that the pathogen was Delta AY.4 variant of 2019-nCoV. Both the epidemiological investigation and the gene sequencing results supported that the local COVID-19 epidemic in Zhenhai was associated with the COVID-19 epidemic in Shanghai. Conclusions: The transmission chain of this epidemic was clear. Delta AY.4 variant has obvious characteristic to cause case clusters in families, places with poor ventilation, and residential communities. It is suggested to strengthen the health management in key areas and key populations, and increase the frequency of nucleic acid testing.

Highly selective microbial transformation of major ginsenoside Rb1 to gypenoside LXXV by Esteya vermicola CNU120806.

AIMS: This study examined the biotransformation pathway of ginsenoside Rb(1) by the fungus Esteya vermicola CNU 120806. METHODS AND RESULTS: Ginsenosides Rb(1) and Rd were extracted from the root of Panax ginseng. Liquid fermentation and purified enzyme hydrolysis were employed to investigate the biotransformation of ginsenoside Rb(1) . The metabolites were identified and confirmed using NMR analysis as gypenoside XVII and gypenoside LXXV. A mole yield of 95·4% gypenoside LXXV was obtained by enzymatic conversion (pH 5·0, temperature 50°C). Ginsenoside Rd was used to verify the transformation pathway under the same reaction condition. The product Compound K (mole yield 49·6%) proved a consecutive hydrolyses occurred at the C-3 position of ginsenoside Rb(1) . CONCLUSIONS: Strain CNU 120806 showed a high degree of specific ß-glucosidase activity to convert ginsenosides Rb(1) and Rd to gypenoside LXXV and Compound K, respectively. The maximal activity of the purified glucosidase for ginsenosides transformation occurred at 50°C and pH 5·0. Compared with its activity against pNPG (100%), the ß-glucosidase exhibited quite lower level of activity against other aryl-glycosides. Enzymatic hydrolysate, gypenoside LXXV and Compound K were produced by consecutive hydrolyses of the terminal and inner glucopyranosyl moieties at the C-3 carbon of ginsenoside Rb(1) and Rd, giving the pathway: ginsenoside Rb(1) → gypenoside XVII → gypenoside LXXV; ginsenoside Rd→F(2) →Compound K, but did not hydrolyse the 20-C, ß-(1-6)-glucoside of ginsenoside Rb(1) and Rd. SIGNIFICANCE AND IMPACT OF THE STUDY: The results showed an important practical application on the preparation of gypenoside LXXV. Additionally, this study for the first time provided a high efficient preparation method for gypenoside LXXV without further conversion, which also gives rise to a potential commercial enzyme application.

Evaluation of immune response and protection in animals given mink parvovirus vaccines.

In orthogonal and pair design tests, mink, guinea-pigs and rabbits were inoculated with inactivated mink enteritis virus (MEV) vaccine prepared with mineral oil or Al(OH)3 gel adjuvant. The animals were examined for serum haemagglutination-inhibition (HI) antibody during 6-55 days postvaccination (p.v.) and serum-neutralizing (SN) antibody for 11-31 days p.v. Differences between mineral oil and Al(OH)3 gel adjuvant vaccines in the induction of HI and SN antibodies during 6-55 days p.v. were not significant. There was significant positive rank correlation between HI antibody level and SN antibody index from 11 to 31 days p.v. in serum of mink inoculated with the mineral oil or Al(OH)3 gel adjuvant vaccine (P < 0.05). The results of experimental challenge tests with vaccines in 29 mink showed a positive correlation between HI antibody titres, SNI and immune protective rates. Levels of HI antibodies in guinea-pigs, rabbits or mink during 11-40 days p.v. were reliable indices for monitoring the humoral immune responses and immune protective rates. The criteria for virus vaccine potency and vaccine immune efficiency is an HA titre of 64 for the cell-cultured MEV and an HI antibody titre of 32 for guinea-pigs, rabbits or mink during 11-40 days p.v. The vaccine stimulates a protective response which lasts for a period of 12 months. The vaccine is stable for a period of 9 months at 4 degrees C. Economic, simple and scientific means have been developed to monitor the quality of MEV vaccines, of which more than 70,000 doses of the mineral oil vaccine and more than 18,000,000 doses of the Al(OH)3 gel vaccine have been used for the last 5 years.

[Studies on function of vegetative nervous system in cardiopathic patients with heart-qi deficiency syndromes and heart-yin deficiency syndromes].

To explore the changes of the function of vegetative nervous system in the patients with the syndromes of Heart-Qi Deficiency (HQD) and Heart-Yin Deficiency (HYD), 53 cases of heart diseases were divided into HQD and HYD, the duration between heart beats, differences of blood pressure in the lying and standing position, and urine-catecholamine/24 hrs was determined separately, and compared with control group. The results showed that the duration between heart beats and heart rate in the lying position in those patients of HQD didn't manifest significant difference with control group. But in 78.9% of patients, the differences of heart rate in expiration/inspiration, surpassed 15 beats per minute, and the proportion of 30/15 was less than 1.03. Compared with control group, the difference was significant (P < 0.01). Meantime, the differences of heart rate of lying/standing position was less than 15 beats per minute, and the difference of blood pressure had an increasing tend in 47.4% of the cases. Those patients of HYD didn't show any difference in the above indexes. Urine-catecholamine/24 hrs in both of the two groups surpassed that of control group (P < 0.01). In short, this study showed that syndromes of HQD and HYD both displayed disturbed function of the vegetative nervous system, and their types and severities were correlated with the difference of Syndromes.

Studies on preparation of inactivated vaccines from cell cultures of mink enteritis virus (MEV) and their immunity.

In this paper, superhigh reproductive rate strains of MEV with titre more than HA8192x or TCID50 log10(9.7) have been achieved both by cultivation in cell lines with different susceptibility to MEV and by isolating and identifying in field by the author. The systematic tests proved that S18 and L12 strains of MEV are the best strains for vaccine preparation. In this study, the best means for the tissue cultivation of MEV and the most advanced technological process for the production and detection of serum-free cell-cultured MEV fluids with super-high HA titre in batches in large quantities have been established for the first time. Optimum conditions for MEV inactivation were determined, and safe and effective inactivated vaccines with mineral oil or Al(OH)3 gel adjuvant were successfully prepared with serum-free cell-cultured MEV fluids. Both vaccines with different adjuvants can be manufactured in batches in large quantities and have been widely used all over China since 1986. The change laws of the immune response kinetics of the MEV vaccines have been determined by the tests, and the indexes and laboratory animal models for monitoring humoral immune efficiency and immune protective rate of parvovirus vaccines have been established for the first time. The manufacturing and monitoring operation rules of the MEV vaccines with different adjuvants have been laid down by the author.