AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.

Aim To express and purify rhα-Gal A with a 6 X His tag via using a serum-free expression system in high-density suspension culture of Chinese hamster ovary cells ( CHO-S) , and to verify the scavenging effect of rhα-Gal A on globular trisaccharide ceramide (Gb3 or GL3) . Methods The construction of recombinant protein expression vector, pcDNA4-GLA, was achieved by fusing the human α-galactosidase cDNA, gla, with 6 X His tag and artificial DNA synthesis. The expression plasmid was transfected into the suspended CHO-S to express rhα-Gal A and then purified. Following this procedure, we determined rhα-Gal A's expression, the enzymatic activity, and the glycosylation of the recombinant enzyme. Co-incubation with cultured cells was performed to examine whether rhα-Gal A could be taken up into the cells and effectively remove Gb3 substrates. Results rhα-Gal A was successfully expressed and purified after transiently transfecting pcDNA4-GLA into the suspended CHO-S, and the yield was up to (100 ±20. 6) mg • L

Objective - （ ）- （ ） To observe the effects of renin angiotensin Ang aldosterone system RAAS in workers exposed to Methods - - occupational noise. Forty five workers with suspected occupational noise induced deafness were selected as noise ， ， exposure group using convenient sampling method. According to their tinnitus symptom noise exposure intensity and work age - ， ， they were divided into no tinnitus and tinnitus subgroups <90 dB and ≥90 dB subgroups work years <10 years and ≥10 years subgroups. Another 45 workers with no occupational noise exposure history were selected as control group. The levels of plasma （ ）， ， ， renin activity PRA AngⅠ AngⅡ and aldosterone of the two groups were detected and the aldosterone to renin activity Results ratio was calculated. The diastolic blood pressure of the noise exposure group was higher than that of the control group ［（ ）vs（ ） ，P ］ ， 80±7 76±8 mmHg <0.05 . However there was no significant difference in systolic blood pressure between the two （P ） （ ： groups >0.05 . The level of plasma AngⅡ in the noise exposure group was higher than that in the control group median vs ，P ） （ P ） 100.98 65.43 μg/L <0.05 . There was no statistical significance in other indexes between the two groups all >0.05 . The （ ： plasma AngⅡ level in < 90 dB subgroup in the noise exposure group was higher than that of the control group median 123.16 vs ，P ） 65.43 μg/L <0.05 . There was no statistical significance in other indexes among the two subgroups of tinnitus symptom or （ P ） work age in the noise exposure group and the control group all >0.05 . There were no significant differences in the abnormal ， （ P ） rates of PRA AngⅡ and aldosterone in plasma between the noise exposure group and the control group all >0.05 . Conclusion Occupational noise exposure may affect RAAS and lead to increased plasma AngⅡ levels in the workers. - Tinnitus and work age may not affect RAAS in occupational noise exposure workers.

Objective - （ ）- （ ） To observe the effects of renin angiotensin Ang aldosterone system RAAS in workers exposed to Methods - - occupational noise. Forty five workers with suspected occupational noise induced deafness were selected as noise ， ， exposure group using convenient sampling method. According to their tinnitus symptom noise exposure intensity and work age - ， ， they were divided into no tinnitus and tinnitus subgroups <90 dB and ≥90 dB subgroups work years <10 years and ≥10 years subgroups. Another 45 workers with no occupational noise exposure history were selected as control group. The levels of plasma （ ）， ， ， renin activity PRA AngⅠ AngⅡ and aldosterone of the two groups were detected and the aldosterone to renin activity Results ratio was calculated. The diastolic blood pressure of the noise exposure group was higher than that of the control group ［（ ）vs（ ） ，P ］ ， 80±7 76±8 mmHg <0.05 . However there was no significant difference in systolic blood pressure between the two （P ） （ ： groups >0.05 . The level of plasma AngⅡ in the noise exposure group was higher than that in the control group median vs ，P ） （ P ） 100.98 65.43 μg/L <0.05 . There was no statistical significance in other indexes between the two groups all >0.05 . The （ ： plasma AngⅡ level in < 90 dB subgroup in the noise exposure group was higher than that of the control group median 123.16 vs ，P ） 65.43 μg/L <0.05 . There was no statistical significance in other indexes among the two subgroups of tinnitus symptom or （ P ） work age in the noise exposure group and the control group all >0.05 . There were no significant differences in the abnormal ， （ P ） rates of PRA AngⅡ and aldosterone in plasma between the noise exposure group and the control group all >0.05 . Conclusion Occupational noise exposure may affect RAAS and lead to increased plasma AngⅡ levels in the workers. - Tinnitus and work age may not affect RAAS in occupational noise exposure workers.

OBJECTIVES: To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance. METHODS: A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission. RESULTS: A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05). CONCLUSIONS Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.
Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Hyperbilirubinemia, Neonatal/therapy* ; Infant, Newborn ; Obstetrics ; Patient Discharge ; Pregnancy ; Retrospective Studies

To investigate the potential molecular mechanism of the combination of Platycodonis Radix and Lilii Bulbus with the homology of medicine and food in the treatment of pneumonia by means of network pharmacology and in vitro verification experiment. Under the condition of bioavailability(OB)≥30% and drug-like(DL)≥0.18, the active components of Platycodonis Radix and Lilii Bulbus were screened in TCMSP database; the prediction targets of active components were searched from TCMSP, DrugBank and other databases, and the potential targets of pneumonia were obtained through GeneCards and OMIM database. The common targets were obtained by the intersection of drug and disease targets. The PPI network of common targets was constructed by STRING 11.0, and the core targets were obtained by topological analysis. Then the core targets received GO and KEGG analysis with use of WebGestalt and Metascape. The "component-target-pathway" network was constructed with the help of Cytoscape 3.7.1 software, and the component-target molecular docking verification was carried out with Discovery Studio 2016 software. Finally, the core targets and pathways were preliminarily verified in vitro. In this study, 12 active components were screened, 225 drug prediction targets and 420 potential diseases targets were obtained based on data mining method, and 14 core targets were obtained by topological analysis, including TNF, MMP9, AKT1, IL4 and IL2. The enrichment results of GO and KEGG showed that "Platycodonis Radix and Lilii Bulbus" drug pair may regulate inflammation, cell growth and metabolism by acting on 20 key signaling pathways such as TNF and IL-17, thereby exerting anti-pneumonia effects. The results of molecular docking showed that 12 active components had good binding ability with 14 core targets. In vitro experiment results showed that the core components of "Platycodonis Radix and Lilii Bulbus" drug pair could inhibit the expression of MMP9 and TNF-α by regulating TNF signal pathway. This study confirmed the scientificity and reliability of the prediction results of network pharmacology, and preliminarily revealed the potential molecular mechanism of the compatibility of Platycodonis Radix and Lilii Bulbus in the treatment of pneumonia. It provides a novel insight on systematically exploring the mechanism of the compatible use of Platycodonis Radix and Lilii Bulbus, and has a certain reference value for the research, development and application of new drugs.
Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pneumonia/drug therapy* ; Reproducibility of Results

Objective : To investigate the application of digital immediate implant and angle screw channel abutment in the aesthetic area and the related influencing factors by reviewing the data of one case of immediate implant repair of the upper anterior teeth and related literature. Methods: One case of refractory chronic apicitis of the upper anterior teeth involved immediate implantation after extraction. The digital information of the patient was obtained by CBCT and intraoral scanning. According to the information from the patients, a preoperative evaluation was performed; a treatment scheme was formulated; a minimally invasive extraction was performed; implants were placed under a digital guide plate; and temporary restoration was immediately performed. Six months after the operation, the patients underwent individualized mold removal, and angle screw channel fixation was completed. We observed the cosmetic effects and soft and hard tissue and gingival contour maintenance effects after restoration and reexamined the patients 6 months after restoration. In addition, the relevant literature was reviewed. Results : The height of the gingival margin and gingival papilla and gingival contour of this patient were well maintained. The red and white aesthetic effect was good. There was no redness or swelling of the gingiva nor obvious changes in the soft and hard tissues around the implant 6 months after restoration, and the patient was satisfied. The results in the literature review show that a preoperative design based on CBCT and intraoral scanning data combined with digital software and a whole digital guide plate make the procedure more accurate and safer. These factors can not only avoid important anatomical structures and serious surgical complications but can also result in implantation in the best three-dimensional position. In addition, the application of digital impression technology and CAD/CAM increases the efficiency, speed, accuracy, simplicity, and comfort of oral impressions and the construction of temporary and final prostheses more precise and faster, greatly improving clinical efficiency. Conclusion Digital immediate implant and angle screw channel abutment is a good method to restore the aesthetics and function of missing teeth and to avoid the complications caused by adhesive residue.

Snake bite is a common acute and severe disease in tropical and subtropical regions, and its public health importance has been largely neglected. Snake venom is a complex mixture of active proteins, polypeptides, and other toxins. Many of these components can target multiple ion channels, cell receptors, and membrane transporters. Compared with traditional small molecule drugs, the proteins and polypeptides from snake venom have stronger specificity and affinity to targets and are especially suitable for novel drug design. The current studies show that snake venom and its components have great potential for development as leading compounds of new drugs. In this paper, the recent advances in main components, toxic effects, and detoxification strategies of snake venom, as well as its pharmacological activities and medical application are reviewed. The aim is to provide reference for clinical diagnosis and treatment of snake bite and development of new drugs based on snake venom.

OBJECTIVE: To investigate the incidence of severe neonatal hyperbilirubinemia and the management on the treatment and follow-up of this disease in Jiangsu Province, China. METHODS: The neonates with severe hyperbilirubinemia who were admitted to 13 hospitals in Jiangsu Province from January to December, 2018, were enrolled as subjects. A retrospective analysis was performed on their mediacal data and follow-up data. RESULTS: In 2018, 740 neonates with severe hyperbilirubinemia were reported from the 13 hospitals in Jiangsu Province, accounting for 2.70% (740/27 386) of the total number of neonates admitted to the department of neonatology. Among these neonates, 620 (83.8%) had severe hyperbilirubinemia, 106 (14.3%) had extremely severe hyperbilirubinemia, and 14 (1.9%) had hazardous hyperbilirubinemia. Four neonates (0.5%) were diagnosed with acute bilirubin encephalopathy. A total of 484 neonates (65.4%) were readmitted due to severe hyperbilirubinemia after discharge from the delivery institution, with a median age of 7 days, among whom 214 (44.2%) were followed up for jaundice at the outpatient service before readmission, with a median age of 6 days at the first time of outpatient examination. During hospitalization, 211 neonates (28.5%) underwent cranial MRI examinations, among whom 85 (40.3%) had high T1WI signal in the bilateral basal ganglia and the globus pallidus; 238 neonates (32.2%) underwent brainstem auditory evoked potential examinations, among whom 14 (5.9%) passed only at one side and 7 (2.9%) failed at both sides. The 17 neonates with acute bilirubin encephalopathy or hazardous hyperbilirubinemia were followed up. Except one neonate was lost to follow-up, and there were no abnormal neurological symptoms in the other neonates. CONCLUSIONS Neonates with severe hyperbilirubinemia account for a relatively high proportion of the total number of neonates in the department of neonatology. Jaundice monitoring and management after discharge from delivery institutions need to be strengthened. For neonates with severe hyperbilirubinemia, relevant examinations should be carried out more comprehensively during hospitalization and these neonates should be followed up comprehensively and systematically after discharge.
Bilirubin ; China ; Evoked Potentials, Auditory, Brain Stem ; Humans ; Hyperbilirubinemia, Neonatal ; Infant, Newborn ; Retrospective Studies

【Objective】Fibroscan has been recommended by multiple clinical guidelines as the first choice among the non-invasive tools for evaluating hepatic steatosis and liver stiffness. The study herein assessed the factors related to the success rate and reliability of the measurement.【Methods】A total of 788 volunteers from Year 2018′ s staff physical checkup in The First Affiliated Hospital of Sun Yat- sen University were recruited. Relationship between age ，gender， body mass index ，waist circumference of the subjects ，and the operator′s experience ，and their effect on success rate and reliability were analyzed.【Results】had a higher detection rate for fatty liver as compared with ultrasound（55.9% vs.39.9% ，P<0.001）. Detection failure and unreliable measurements occurred in only 1.4% of all the participants. Success rate was not associated with gender ，but decreased significantly with increased age ，body mass index and waist circumference （P<0.05）. LSM IQR/Median increased accordingly ，thus reduced the reliability of the measurement. With accumulated number of measurements by the same operator，so did the success rate and reliability of the results. An operator with more than 300 measurements could be deemed as experienced operator.【Conclusions】The success rate and reliability of the measurement was affected by increased age ，body mass index ，waist circumference and operator′ s experience. Fixed operator could also achieve very high success rate and reliable measurement using Fibroscan after short- term training.