Objective To investigate the current status and awareness of pharmaceutical services in hospitals in Guizhou province and to provide a reference for exploring and carrying out pharmaceutical service fees.Methods The questionnaire was designed by the"wjx.cn"website.Three kinds of questionnaires were designed for pharmacists,doctors,nurses,and patients as the research objects,with corresponding differences in some questions,and promoted on WeChat,Dingxiangyuan,and other network platforms.Results A total of 655 questionnaires were collected,and 639 valid questionnaires were recovered,with an effective recovery rate of 97.56%.324 pharmacists(50.70%),82 doctors and nurses(12.83%),233 patients(36.46%)were surveyed.The average approval score of these three groups of respondents on pharmaceutical service fees was 4.67,4.23,and 4.22,respectively(full score:5).Conclusions Overall,pharmacists'professional services have received support from medical staff and patients.However,patients'pharmaceutical service projects currently focus on dispensing services.The recognition of pharmacists'work and the public's awareness of pharmaceutical services can be improved by enhancing the professional ability of pharmacists,strengthening publicity and guidance,and exploring"Internet+pharmaceutical services",etc.,to promote the sustainable development of pharmaceutical services.

Objective:To evaluate the clinical efficacy and safety of secukinumab in the treatment of moderate to severe the adults with plaque psoriasis.Methods:The clinical data from 183 adult patients with moderate to severe plaque psoriasis treated with secukinumab were collected.The patients received subcutaneous injections of secukinumab once a week at weeks 0,1,2,3,and 4,followed by an injection every 4 weeks,with each dose of 300 mg.The follow-up period was 52 weeks.The psoriasis area and severity index(PASI),body surface area(BSA),investigator global assessment(IGA),and dermatology life quality index(DLQI)scores of the patients with psoriasis were caculated.The clinical efficacy and safety of secukinumab in the treatment of moderate to severe plaque psoriasis were evaluated,and the influencing factors were analyzed.Results:Compared with week 0,the PASI、BSA、IGA and DLQI scores of the patients were significantly decreased at weeks 4,12,24,and 52 of secukinumab treatment(P<0.05).After treated with secukinumab,the percentages of the patients achieving PASI 75,PASI 90,and PASI 100 at week 4 were 95.6%,84.2%,and 47.5%,respectively;at week 12,they were 97.3%,95.6%,and 78.7%,respectively;at week 24,they were 97.8%,96.7%,and 84.2%,respectively;and at week 52,they were 98.4%,97.8%,and 83.6%,respectively.The percentages of the patients with BSA≤1%at weeks 4,12,24,and 52 were 80.9%,94.5%,95.6%,and 94.0%,respectively.The percentages of the patients with IGA score of 0/1 at week 4,12,24,and 52 were 86.3%,97.3%,96.7%,and 95.6%,respectively.The percentages of the patients with DLQI score of 0/1 at weeks 4,12,24,and 52 were 76.6%,89.1%,92.9%,and 91.8%,respectively.At week 4 of secukinumab treatment,there were significant differences in age,body mass index(BMI),disease duration,baseline PASI score,and history of previous biologic treatment between the patients in two groups(P<0.05).At week 24 of secukinumab treatment,there were significant differences in age and BMI between the patients in two groups(P<0.05).At week 4,BMI≥25 kg·m-2,disease duration≥10 years,baseline PASI score≥10,and a history of previous biologic treatment were risk factors affecting the recovery of the patient(P<0.05).At week 24,age≥40 years was a risk factor affecting the recovery of the patient(P<0.05).During the treatment period,44 out of 183 psoriasis patients reported 49 adverse reactions,and the adverse reaction rate was 24.0%.No serious adverse events or fatal adverse reactions occurred.The adverse reactions included upper respiratory tract infections in 23 cases,eczema-like skin lesions in 10 cases,skin fungal infections in 6 cases,urticaria in 3 cases,mild liver function abnormalities in 2 cases,folliculitis in 2 cases,conjunctivitis in 2 cases,and otitis media in 1 case.Conclusion:Secukinumab treatment for the adult patients with moderate to severe plaque psoriasis is rapid-acting and has lasting efficacy.The BMI,disease duration,baseline PASI score,history of previous biologic treatment,and age are the factors influencing the clinical efficacy of secukinumab.The overall safety is good,and secukinumab may be used as a first-line treatment option for moderate to severe plaque psoriasis.

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

Objective:To investigate the association between gene polymorphisms in vitamin D receptor(VDR) and Tourette syndrome (TS).Methods:The genetic contributions of VDR FokI (rs2228570), BsmI (rs1544410), and Cdx2 (rs11568820) polymorphisms were genotyped by TaqMan allelic discrimination real-time (RT)-PCR, which evaluated by a case-control analysis in 417 TS patients and 442 healthy controls, and followed by a family-based study in 417 TS trios.Chi-square test and relative risk analysis were conducted by IBM SPSS 23.0 software.Results:FokI (rs2228570) had three genotypes(CC=109, CT=235, TT=73); BsmI (rs1544410) had three genotypes(AA=2, AG=45, GG=370); Cdx2 (rs11568820) had three genotypes(AA=71, AG=200, GG=146). No significant difference in genotype ( χ2=5.516, P=0.063; χ2=3.466, P=0.177; χ2=0.561, P=0.755, respectively) or allele frequencies( χ2=0.840, P=0.359; χ2=3.376, P=0.066; χ2=0.051, P=0.822, respectively)of FokI, BsmI and Cdx2 were identified between TS patients and control groups.No significant over-transmission was identified for these three polymorphisms among 417 TS trios in the family-based study (TDT for FokI: χ2=0.009, P=0.962; for BsmI: χ2=1.220, P=0.320; and for Cdx2: χ2=0.260, P=0.646). Haplotype relative risk (HRR) analysis and haplotype-based haplotype relative risk (HHRR) analysis showed no significant difference in allele frequencies distribution of FokI, BsmI and Cdx2 (all P>0.05). Conclusion:VDR receptor gene polymorphism has no effect on TS susceptibility in the Chinese Han population. However, a potential role of VDR should be explored in more polymorphisms, different populations and larger samples.

ObjectiveTo explore the characteristics of oral sensory-motor function in children with functional articulation disorders (FAD). MethodsFrom June, 2021 to January, 2022, 61 children with FAD in the Department of Children's Health of the Affiliated Hospital of Qingdao University were as case group, 90 normal healthy children were as control group. They were assessed with Oral Sensory-Motor Assessment, and were compared among different genders and different ages. Hyperactivity problems were assessed using Conners Parent Symptoms Questionnaire, and their oral sensory-motor function were compared between patients with hyperactivity problem (n = 13) and without hyperactivity problem (n = 48). ResultsThe total score and the scores of oral sensation, mandibular motion, lip motion and tongue motion were significantly lower in the case group than in the control group (t > 4.471, P < 0.001). There were significant differences in the total score and motor function scores among different ages in the control group (H > 17.015, P < 0.001), and they increased with age. There were significant differences in the total score, oral sensory and motor function scores among different ages in the case group (H > 10.567, P < 0.01), and they increased with age. The total scores, and the scores of mandibular, lip and tongue movements were lower in the boys and girls of the case group than in the same gender of the control group (t > 2.49, P < 0.05). The total score and the scores of the lip and tongue movements were lower in boys than in girls in the case group (|Z| > 2.409, P < 0.05). There was no significant difference in the total score and other scores between the patients with hyperactivity problem and without hyperactivity problem (P > 0.05). ConclusionThe oral sensory-motor function is poor for children with FAD, and can develop with age in both normal and FAD children.

Objective:To explore the levels of vitamin A(VA) and vitamin D(VD) in blood of children with tic disorder (Tic disorder, TD) and their associations with tic symptoms severity and clinical types, so as to provide evidence for better prevention and treatment of TD.Methods:A total of 245 children with TD from September 2018 to April 2019 in the department of child Health care, affiliated hospital of qingdao university were enrolled as the case group and 63 healthy children who underwent routine physical examination at the same time as the control group. The levels of VA and VD were measured and their relationship with the severity of tic symptoms and clinical types were analyzed.Results:(1)The VD level of the case group was significantly lower than that of the control group ((23.72±8.87) μg/L , (26.61±7.59) μg/L, t=-2.24, P=0.03), and the proportion of insufficiency or even lack (37.31%, 75/201) was higher than the control group (15.79%, 9/57) (χ 2=9.37, P=0.002). (2)According to the Yale global tic severity scale(YGTSS), the children in the case group were divided into mild TD group, and moderate-to-severe TD group. ①There were significant differences in serum VA and VD levels in mild TD group, moderate-to-severe TD group and the control group ( F=29.79, P<0.01; F=10.90, P<0.01). Among them, the content of VA and VD in moderate-to-severe TD group were lower than those in mild TD group and control group (VA: (0.29±0.06)mg/L, (0.35±0.06)mg/L, (0.34±0.06)mg/L; VD: (21.01±8.30)μg/L, (25.84±8.76)μg/L, (26.61±7.59)μg/L). ②VA and VD levels of children with TD were negatively correlated with the severity of symptoms ( r=-0.325; P<0.01; r=-0.228; P=0.001). (3)According to DSM-V classification criteria, TD children were divided into PTD group, CTD group and TS group. ①There was no significant difference in serum VA level among different clinical types of TD children ( F=0.87, P=0.46). ②The levels of serum VD were different among the four groups ( F=4.13, P=0.007). Among them, the VD level in TS group was the lowest, and its content was significantly lower than that in control group ((21.83±7.60)μg/L, (26.61±7.59)μg/L, P<0.05)). The prevalence of insufficient or even lack of serum VD in children with different subtypes of TD was higher than that in the control group (χ 2=10.88, P=0.01). Conclusion:Vitamin D deficiency exists in children with TD. The level of vitamin A and vitamin D in serum of children with TD is related with the severity of tic symptoms.The VD level is related with clinical type of TD.

Objective: To explore the relationship between childhood depressive symptoms with behaviors and family factors, and to provide a new perspective for comprehensive treatment of depressive children. Methods: A total of 58 children diagnosed with depressive disorder were recruited as case group in Department of Child Health, Affiliated Hospital of Qingdao University. At the same time, 88 healthy children were selected as age and gender-matched control group. Depressive symptoms, behaviors and family factors in the two groups were investigated. SPSS 22.0 statistical software was used to describe and analyze the data. Results: The total score of CBCL scale in the case group was significantly higher than that in the control group(43.29±30.93, 20.24±12.93, P<0.01), and the number of positive factors was significantly higher than that in the control group(2.57±3.14, 0.97±1.80, P<0.01). The scores of introversion, extroversion, depression, compulsion, hyperactivity, aggression and social withdrawal in the case group were significantly higher than those in the control group(30.29±26.10, 17.10±16.53; 26.29±26.88, 17.45±16.99; 10.14±10.23, 3.48±3.14; 7.29±7.31, 4.83±5.26; 7.00±7.01, 4.86±4.38; 12.86±11.60, 8.38±8.90; 4.29±5.14, 2.72±3.01, P<0.01). There was no significant difference between the two groups in the scores of physical complaints and disciplinary violations (P>0.05). The scores of somatization, hostility and terror of SCL-90 in parents of children in case group were significantly higher than those in control group(17.58±4.05, 15.81±4.00; 9.66±2.67, 8.69±2.45; 8.03±1.49, 7.50±0.88, P<0.05). The score of SDS scale was positively correlated with the total score of CBCL scale, the number of positive factors, introversion, extroversion, depression, compulsion, hyperactivity, aggression and social withdrawal, and negatively correlated with parents’ marital status (P<0.01). Conclusion Depression is a common emotional disorder in childhood, which has a negative impact on learning and social performance. In the comprehensive treatment of children with depression, the importance of child behavior therapy and parental psychological counseling should be fully considered for mental health improvement.

Objective To explore the association between the GRIN3B gene and Tourette syndrome (TS) in children by screening mutations in the coding region of this gene.Methods Fifty-one children with TS and their parents in the Affiliated Hospital of Qingdao University from October 2015 to November 2016 were selected as an experimental group,41 cases of boys,and 10 cases of girls,aged 6-16 years[(9.78 ±3.64)years],while 60 people aged 22-45 years in the health examination center were selected in the control group,49 cases were male,1 1 cases were female,aged 22-45 years [(29.08 ± 2.89) years].DNA was extracted from 51 patients with TS,their parents and 60 controls.PCR was applied to amplify the encoding region of GRIN3B gene and Sanger sequencing was used to sequence,then GRIN3B sequencing results were compared with the NCBI gene encoding region sequence (NM_138690.2)to test whether these patients carried gene mutation and to verify the findings from their family.Results c.C460T gene variant of GRIN3B was found in 2 patients (p.P154S);c.T1187C (p.L396S) variant of GRIN3B gene was found in 10 patients and both of abnormal GRIN3B sites lead to changes in amino acid.The 2 peak sequencing maps were obtained by Sanger sequencing but nothing was found in their parents.Conclusion The mutation of GRIN3B gene may be related to the development of TS.

Objective To explore the effects of different anesthesia methods on postoperative TLR4 expression and the level of serum S100β protein in children.Methods Totally 122 children with elective surgery were randomly divided into two groups.The control group was treated with ketamine intravenous anesthesia,while the observation group was treated with inhalation anesthesia with sevoflurane.Expression of TLR4,the level of serum S100β protein and the adverse reactions of anesthesia were observed.Results During the period of anesthesia,the incidence rates of physical and mental symptoms in the observation group were significantly lower than the control group (P ＜ 0.05).The levels of serun S100β protein at 2 h and 24 h after operation in the observation group were significantly lower than those in the control group (P ＜ 0.05).Compared with those before operation,there was no significant difference in the expression of TLR4 at the time of skin incision,2 h and 24 h after operation (P ＞ 0.05).The expressions of TLR4 at the time points of after skin incision,2 h and 24 h after operation in the control group were significantly lower than those before operation and the observation group (P ＜ 0.05).Conclusion The sevoflurane inhalation anesthesia can reduce the adverse reactions of anesthesia in children with surgery.