OBJECTIVE:To prepare Geinstein (GEN) solid dispersion,and improve the dissolution rate of GEN in vitro. METHODS:Using PVP K30,PEG6000,and PEG4000 as carriers,GEN solid dispersion was prepared by solvent melting meth-od,and its dissolution in vitro was investigated. The structure of the solid dispersion was characterized by FTIR and DSC. RE-SULTS:GEN solid dispersion prepared with PEG4000 as carrier was better than those with other carriers in dissolution,and drug-carrier ratio (1:5) was the best. The results of DSC and FTIR showed that GEN in solid dispersion took amorphous form. CONCLUSIONS:GEN solid dispersion is prepared successfully and significantly improve the dissolution of GEN in vitro.

Objective To optimize the prescription of preparation technology of Xiaoer Qingfei Dispersible Tablets. Methods The filler, disintegrant, adhesive, lubricant, and drug loading were screened by single factor tests. The combined application proportion of three disintegrating agents, PVPP, CMS-Na, and L-HPC, were optimized by orthogonal test. Results The best prescription of preparation technology of dispersible tablets:microcrystalline cellulose as filler;silica gel powder as lubricant;75%alcohol as the adhesive;PVPP, L-HPC, and CMS-Na as combined disintegrants (L-HPC∶PVPP∶CMS-Na=4∶3∶6). The disintegration time of prepared dispersible tablets was less than 3 minutes, and all through the No.2 sieve. Dispersible uniformity was in accordance with the provisions. Conclusion Xiaoer Qingfei Dispersible Tablets prepared by the optimized preparation process are stable and feasible, and suitable for clinical application.

Objective To observe the inhibitory effects of Typhonium Giganteum soft capsules on tumor growth in Hep-2 tumor-bearing nude mice and its effects on the expression of tumor suppressor p53 gene; To discuss its mechanism of action.Methods Human liver cancer Hep-2 cell suspension back subcutaneous vaccination was conducted to prepare tumor models. BALB/c nude mice were randomly divided into model group, cisplatinum group, and TCM high-, medium-, and low-dose groups. Each group was given relevant medicine for gavage, once a day for 21 days. Growth changes of tumor volume were monitored; HE staining was used to observe pathological changes of tumor tissues; RT-PCR was used to detect the expression of p53 gene in tumor tissue of Hep-2 nude mice.Results Compared with the model group, all medication groups could inhibit the tumor growth, and the anti-tumor rates were 55.1%, 42.8%, 30.1%, and 79.5%, respectively; the expression of p53 gene increased; pathological observation results showed that the number and the volume of tumor cells increased, with cytoplasm rarefaction and nucleus anachromasis. All medication groups had karyopyknosis, slight staining, and decreasing blood capillary and focal necrosis in varying degrees.ConclusionTyphonium Giganteum soft capsules can inhibit the growth of human liver cancer, and its mechanism may be associated with the up-regulating expression of p53 gene leading to apoptosis.

Objective To evaluate the clinical benefits and safety of endoscopic thyroidectomy via bilat -eral-nipple approach and breast approach by comparison with conventional open thyroidectomy .Methods 59 pa-tients undergoing open thyroidectomy , 76 patients undergoing endoscopic thyroidectomy via breast approach , and 122 patients undergoing endoscopic thyroidectomy via bilateral-nipple approach were retrospectively analyzed . Patients'age, operation duration, intraoperative blood loss, the first day drainage volume after operation , postop-erative hospital stay , the incidence of complications , pain visual analogue score ( VAS) , postoperative satisfaction rate as well as the evaluation of cosmetic results were compared among different groups .Results No significant difference was observed in the intraoperative blood loss and the postoperative hospital stay among different groups . The operation duration and the first day drainage volume after operation in the endoscopic thyroidectomy groups ((103.5 ±26.2)min vs (108.1 ±23.9)min,(106.5 ±31.0)ml vs (117.4 ±38.8)ml)were significantly high-er than those in the open thyroidectomy group((65.3 ±22.4)min and (50.5 ±23.8)ml)(P<0.05, respective-ly).No significant difference was observed in the complication incidence among different groups .On the first day after operation, VAS of the endoscopic thyroidectomy groups (2.8 ±0.4 vs 2.9 ±0.4)was significantly lower than that of the open thyroidectomy group(3.8 ±0.6)(P<0.05, respectively), even though on the second and the third day no significant difference was observed among different groups .Besides, postoperative satisfaction rate and the evaluation of cosmetic results in endoscopic thyroidectomy groups were significantly higher than those in the open group(P<0.05, respectively).Furthermore, 90 days after operation, the satisfaction rate and the eval-uation of cosmetic results in the endoscopic thyroidectomy group through bilateral -nipple approach (96.7%,8.8 ± 0.9)were significantly higher than those in the endoscopic thyroidectomy group through breast approach (92.1%, 7.3 ±0.7)(P<0.05, respectively).Conclusions Endoscopic thyroidectomy is a feasible and safe procedure . Endoscopic thyroidectomy through bilateral-nipple approach has a higher long-term satisfaction rate as well as bet-ter cosmetic results , which is an ideal choice of thyroidectomy .

Objective:To investigate the mechanism of Candida albicans Int1 in regulating septin organization. Methods:A series of full-length and truncated fragments of Int1 were constructed and fused with green fluorescent protein (GFP). The intracellular localization of the fusion proteins was observed under a fluorescence microscope. The region in Int1 that was required for bud neck localization was identified. Full-length and fragments of Int1 were overexpressed in the yeast Saccharomyces cerevisiae and the changes in cell growth, cell morphology and septin organization were investigated to determine the functional region in Int1 that mediated the interaction with septin. Moreover, the co-localization of the region and septin was analyzed. Results:The full-length Int1 consisted of 1 661 amino acid residues. A middle region of 209 amino acid residues, Int1-M4 (739-947 aa), that could be localized at the bud neck during both small and large bud periods was identified. Overexpression of Int1-M4 led to significant growth defects, elongated bud and disorganized septin. In the cells with elongated bud, Int1-M4 and septin with abnormal structures could be co-localized.Conclusions:Int1-M4 (739-947 aa), the middle region of Int1 containing 209 amino acid residues, mediated the bud neck localization and the interaction with septin, playing an important role in regulating septin organization.

Objective:To investigate the clinical features and characteristics of gene mutation of patients with neurodevelopmental disorder caused by CTNNB1 gene. Method:Genetic mutation analysis of the patients were obtained by using the whole exome sequencing and Sanger sequencing. We reviewed the literatures for the clinical and genetic features of CTNNB1 related neurodevelopmental disorder. Results:Six inpatients, three boys and three girls, who came for speech impairment motor delay were included in this study. The average age for the patients was 17.8±11.1 months. The main clinical manifestations of the patients were craniofacial dysmorphism, microcephaly, hypertonia or spasm, speech impairment motor delay, esotropia and valgus. WES showed that 6 patients carried de novo mutations of CTNNB1 gene, which were c.1057delA, c.1493_1494insA, c.418_424del, c.1985_1988del, c.1420C>T and c.1550T>C. No abnormality was found in the patients′ parents. Conclusions:The clinical manifestation of CTNNB1 related neurodevelopmental disorder involves multiple systems. We found five unreported variants and expanded the variation spectrum of the CTNNB1 gene.

Objective:To investigate the efficacy of Qingruxiao granules combined with tamoxifen in the treatment of breast hyperplasia and its effect on serum hypoxia-inducible factor-alpha (HIF-α), angiopoietin-2 (Ang-2) and prolactin (PRL) levels. Methods:Ninety-eight patients with breast hyperplasia admitted to Xi'an No.3 Hospital from June 2020 to January 2022 were retrospectively included in this study. They were divided into control and observation groups ( n = 49/group) according to different treatments. The control group was treated with tamoxifen alone. The observation group was treated with Qingruxiao granules combined with tamoxifen. Clinical efficacy, symptom score, ultrasound parameters (glandular layer thickness, longest diameter of mass, maximum diameter of hypoechoic area, inner diameter of lactating tube), endocrine hormone levels (estradiol, progesterone, and prolactin), HIF-α, and Ang-2 pre- and post-treatment, as well as the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [93.88% (4/49) vs. 77.55%, χ2 = 5.33, P < 0.05). After treatment, breast mass score, breast pain, systemic accompanying symptom, and nipple discharge in the observation group were (1.34 ± 0.29) points, (1.02 ± 0.36) points, (0.68 ± 0.17) points, (0.97 ± 0.15) points, respectively, which were significantly lower than (1.57 ± 0.23) points, (1.45 ± 0.41) points, (0.95 ± 0.26) points, and (1.28 ± 0.26) points, respectively, in the control group ( t = 4.35, 5.52, 6.08, 7.23, all P < 0.001). The glandular layer thickness, the longest diameter of mass, the maximum diameter of hypoechoic area, and the inner diameter of lactating duct in the observation group were (9.45 ± 1.67) mm, (11.46 ± 3.68) mm, (14.37 ± 4.22) mm, and (1.23 ± 0.39) mm, respectively, which were significantly lower than (11.26 ± 2.51) mm, (16.33 ± 4.01) mm, (19.87 ± 5.01) mm, (1.54 ± 0.48) mm in the control group ( t = 4.20, 2.26, 5.88, 3.51, all P < 0.001). Serum estradiol and prolactin levels in the observation group were (122.35 ± 29.76) ng/L and (205.64 ± 36.42) IU/L, respectively, which were significantly lower than (139.76 ± 30.48) ng/L and (251.49 ± 41.87) IU/L in the control group ( t = 2.86, 5.78, both P < 0.05). Serum progesterone level in the observation group was (9.22 ± 1.57) μg/L, which was significantly higher than (7.18 ± 1.21) μg/L in the control group ( t = -7.20, P < 0.05). Serum HIF-α and Ang-2 levels in the observation group were (0.15 ± 0.05) ng/L and (0.98 ± 0.11) ng/L, respectively, which were significantly lower than (0.24 ± 0.07) ng/L and (1.49 ± 0.22) ng/L in the control group ( t = 7.32, 14.51, both P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Qingruxiao granules combined with tamoxifen can effectively improve clinical symptoms, reduce tumor size, regulate endocrine hormone levels, decrease the expression of angiogenic factors in patients with breast hyperplasia, and is highly safe.

The clinical data of 2 patients with LIG4 syndrome who presented to Wuhan Children′s Hospital from May 2020 to December 2021 were retrospectively analyzed and genetically analyzed. Both patients were male, aged from 5 months to 3 years. The clinical presentations were scattered rash and repeated infections (bacterial infection, EB virus, cytomegalovirus, etc). Laboratory tests showed that the neutrophil and lymphocyte counts decreased. Immunoassay revealed a significant is CD4+T, CD8+T, CD19+B lymphocytes and NK. By Whole exome sequencing, we found 2 inherited mutations inherited in the LIG4 gene (c.833G>T and c.1271_1275delAAAGA) from patient1, and another 2 inherited mutations (c.980T>G, c.1271_1275del) from patient 2. In this study, we found two new variants of LIG4 gene and expanded the mutation spectrum of this gene.

Objective:To summarize the electrophysiological characteristics of neuronal intranuclear inclusion disease (NIID) and explore the value of electrophysiological examination in NIID auxiliary diagnosis.Methods:Twenty NIID patients diagnosed by pathological biopsy and genetic confirmation (15 were symptomatic, 5 were asymptomatic), admitted to Department of Neurology, Affiliated Hospital of Xuzhou Medical University from February 2020 to June 2022 were chosen. Peripheral motor/sensory nerve conduction, needle electromyography, F wave, repetitive electrical stimulation, skin sympathetic reflex (SSR), and tremor were analyzed. Peripheral nerve conduction and SSR parameters were compared between 15 patients with symptomatic NIID (symptomatic NIID group) and 11 age- and gender-matched normal control subjects (control group).Results:(1) All 15 patients with symptomatic NIID were with abnormal electrophysiological findings: 14 patients had abnormal peripheral nerve conduction, including 14 with slowed motor nerve conduction velocity (MCV), 4 with reduced composite muscle action potential (cMAP) wave amplitude, 12 with slowed sensory nerve conduction velocity (SCV), and 3 with reduced sensory nerve action potential (sNAP) wave amplitude, and overall slowed nerve conduction velocity and relatively preserved wave amplitude were noted; 4 patients had neurogenic lesions by needle electromyography; 13 patients had prolonged F-wave latency at varied degrees; 12 showed abnormal SSR; 4 exhibited synchronous tremor from 4.0 to 7.5 Hz. (2) In 5 patients with asymptomatic NIID, 3 had abnormal peripheral nerve conduction, including 3 with slowed MCV, 2 with slowed SCV, and 1 with reduced sNAP wave amplitude; 3 showed abnormal SSR. (3) Significant differences in MCV and SCV, some cMAP and sNAP amplitudes, and SSR latency and amplitude were noted in nerves of the upper and lower extremities between the symptomatic NIID group and control group ( P<0.05). Conclusion:Peripheral nerve damages are common in patients with NIID, especially myelin damage and autonomic nerve injury, and some patients may have electrophysiological abnormalities before clinical symptoms; therefore, peripheral nerve conduction and SSR can be recommended as auxiliary screening tools for NIID.