Drug therapy is a common method to cure diseases and relieve symptoms.The value of patient-reported outcome(PRO)in evaluating the effect of drug therapy has been increasingly paid attention.The PRO scale is a standardized questionnaire,which can scientifically evaluate the experiences and subjective effects of drug use from a patient-centered perspective,and help patients and clinicians make more reasonable medication decisions.By reviewing and sorting out relevant global literature,this paper found that the content of the PRO scales relevant to drug therapy focused on five fields:"medication satisfaction""medication adherence""drug treatment burden""medication-related quality of life"and"adverse drug reactions".This paper described the basic information,measurement characteristics and application of common scales in recent years respectively,and summarized and analyzed the problems and enlightenment of scale development,aiming to provide theoretical reference for the selection,application and development of PRO scales.

Objective To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate(NaB)in a mouse model of Parkinson's disease(PD)via the gut-brain axis.Methods Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group,PD model group,and NaB treatment group.In the latter two groups,PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once daily for 5 consecutive days,and normal saline was injected in the control group.After modeling,the mice received daily gavage of NaB(300 mg/kg)or an equal volume of saline for 14 days.Behavioral tests were carried out to assess the changes in motor function of the mice,and Western blotting was performed to detect the expressions of tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the striatum and nuclear factor-κB(NF-κB),tumor necrosis factor(TNF-α),interleukin 6(IL-6),and the tight junction proteins ZO-1,Occludin,and Claudinin the colon.HE staining was used to observe inflammatory cell infiltration in the colon of the mice.RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues,and their expressions were verified using qRT-PCR and Western blotting.Results The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH,Occludin,and Claudin and downregulated expressions of α-syn,NF-κB,TNF-α,and IL-6(all P<0.05).HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice.RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice(P<0.05).Conclusion NaB can improve motor dysfunction,reduce dopaminergic neuron loss in the striatum,and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.

Objective To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate(NaB)in a mouse model of Parkinson's disease(PD)via the gut-brain axis.Methods Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group,PD model group,and NaB treatment group.In the latter two groups,PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once daily for 5 consecutive days,and normal saline was injected in the control group.After modeling,the mice received daily gavage of NaB(300 mg/kg)or an equal volume of saline for 14 days.Behavioral tests were carried out to assess the changes in motor function of the mice,and Western blotting was performed to detect the expressions of tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the striatum and nuclear factor-κB(NF-κB),tumor necrosis factor(TNF-α),interleukin 6(IL-6),and the tight junction proteins ZO-1,Occludin,and Claudinin the colon.HE staining was used to observe inflammatory cell infiltration in the colon of the mice.RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues,and their expressions were verified using qRT-PCR and Western blotting.Results The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH,Occludin,and Claudin and downregulated expressions of α-syn,NF-κB,TNF-α,and IL-6(all P<0.05).HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice.RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice(P<0.05).Conclusion NaB can improve motor dysfunction,reduce dopaminergic neuron loss in the striatum,and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.

Objective:To investigate the effects of intravenous thrombolysis combined with Xingnaojing injection on hemodynamic indexes and neurological function in patients with cerebral infarction. Methods:A total of 142 patients with cerebral infarction who were treated in Xing An Meng Hospital from April 2020 to May 2021 were included in this study. They were randomly divided into a control group ( n = 71, intravenous thrombolysis) and a Xingnaojing injection group ( n = 71, intravenous thrombolysis + Xingnaojing injection). Intracranial arterial hemodynamic indexes, National Institutes of Health Stroke Scale score, Fugl-Meyer Assessment Scale score, serum inflammatory factors, oxidative stress indexes, brain injury markers, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly lower in the Xingnaojing injection group than the control group [interleukin-1β: (4.05 ± 0.83) ng/L vs. (6.85 ± 1.02) ng/L, interleukin-6: (43.61 ± 5.14) ng/L vs. (60.31 ± 7.04) ng/L, tumor necrosis factor-α: (35.93 ± 4.25) ng/L vs. (20.93 ± 3.11) ng/L, t = 17.94, 16.14, 15.37, all P < 0.001]. After treatment, the mean blood flow velocities of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery in the Xingnaojing injection group were significantly higher than those in the control group [anterior cerebral artery: (49.36 ± 5.28) cm/s vs. (41.15 ± 5.12) cm/s, middle cerebral artery: (61.27 ± 7.02) cm/s vs. (50.19 ± 6.08) cm/s, posterior cerebral artery: (44.92 ± 5.63) cm/s vs. (37.26 ± 4.93) cm/s, t = 9.40, 10.05, 8.62, all P < 0.001]. After treatment, the National Institutes of Health Stroke Scale score and Fugl-Meyer Assessment Scale score in the Xingnaojing injection group were superior to those in the control group [National Institutes of Health Stroke Scale score: (10.36 ± 1.52) points vs. (14.62 ± 2.05) points, Fugl-Meyer Assessment Scale score: (76.19 ± 8.08) points vs. (65.28 ± 7.14) points, t = 14.06, 8.52, both P < 0.05]. After treatment, the serum level of malondialdehyde in the Xingnaojing injection group was significantly higher than that in the control group [(6.35 ± 1.02) μmol/L vs. (10.05 ± 1.63) μmol/L), t = 16.21, P < 0.001]. The serum level of superoxide dismutase in the Xingnaojing injection group was significantly lower than that in the control group [(114.31 ± 13.69) U/L vs. (92.25 ± 10.16) U/L), t = 10.90, P < 0.001]. Serum levels of neuron-specific enolase and S100β in the Xingnaojing injection group were significantly lower than those in the control group [neuron-specific enolase: (24.01 ± 3.24) IU/L vs. (30.31 ± 4.02) IU/L, S100β: (0.73 ± 0.17) ng/L vs. (1.13 ± 0.22) ng/L, t = 10.28, 12.12, both P < 0.001). There was a significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Intravenous thrombolysis combined with Xingnaojing injection for the treatment of cerebral infarction can improve intracranial hemodynamics, reduce the inflammatory response and oxidative stress, and alleviate brain tissue injury. The combined therapy is beneficial to protect the neurological function of patients with cerebral infarction and is highly safe.

Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.

Objective:To analyze the genetic characteristics of varicella-zoster virus (VZV) in Liaoning province in 2019.Methods:Vesicle fluid samples were collected from 32 individuals with suspected VZV infection in Liaoning province from 2019. Nucleic acids were extracted, the suspected samples were screened by real-time fluorescent quantitative PCR. Single nucleotide polymorphisms (SNP) sites on ORF22, ORF38 and ORF62 were detected and analyzed in three open reading frames (ORFS) of positive samples. The samples and sequence data were collected and the gene sequences were compared to determine the genotype of the virus strain, and the vaccine strain was identified from the wild strain.Results:In the 32 suspected samples, VZV-positive strains were detected in 27 samples, all belonged to wild-type strain of Clade 2. Compared with Clade 2 referenced strains, the homology of nucleotide and amino acid for all 10 samples were 98.85%-100% and 96.9%-100%, respectively. There was a synonymous mutation (A→G) in position 37990 of LN-14 strain. The nucleotide homology of ORF22 showed that all 27 samples were on the same branch with the Clade 2 referenced strains and had a vaccine breakthrough cases.Conclusions:This study reveals that the VZV strains circulating in Liaoning province in 2019 were all wild-type strains belonging to Clade 2.

OBJECTIVE: To compare the accuracy of five warfarin-dosing algorithms and warfarin stable dose model (2.5 mg/day) for Shandong population. METHODS: One hundred and twenty five patients who achieved stable warfarin dose were enrolled. Clinical and genetic data were used to evaluate the value of each algorithm by calculating the percentage of patients whose predicted warfarin dose was within 20% of the actual stable therapeutic dose and mean absolute error (MAE). RESULTS: The frequency of patients with CYP2C9*1/*1, CYP2C9*1/*3 and CYP2C9*1/*2 genotype was 92.00%, 7.20%, 0.80%, respectively. That of VKORC1-1639 AA, AG and GG genotype was 82.40%, 15.20%, 2.40%, respectively. CYP4F2*1/*1, *1/*3, *3/*3 genotype was 50.40%, 39.20%, 10.40%, respectively. With the same genotypes for other loci, patients who carried at least one VKORC1-16398G mutant allele had increased warfarin stable daily dose compared with VKORC1-1639AA. Compared with CYP4F2*1/*1, those carrying at least one CYP4F2*3 mutant allele had warfarin stable daily dose increased by 5.9%-13.00%. The percentage of ideal prediction calculated from IWPC model (59.20%), Huang model (57.60%) and Ohno model (52.80%) were higher than others. The MAE were 0.35 (95%CI: 0.11-0.49), 0.15 (95%CI: 0.10-0.32), 0.39 (95%CI: 0.12-0.51), respectively. CONCLUSION The polymorphisms of CYP2C9, VKORC1 and CYP4F2 genes can influence the stable dose of warfarin in Shandong population. IWPC algorithm is suitable for guiding the use of warfarin in this population.
Anticoagulants ; administration & dosage ; Aryl Hydrocarbon Hydroxylases ; Cytochrome P-450 CYP2C9 ; genetics ; Cytochrome P450 Family 4 ; genetics ; Dose-Response Relationship, Drug ; Genotype ; Humans ; Models, Theoretical ; Polymorphism, Genetic ; Vitamin K Epoxide Reductases ; genetics ; Warfarin ; administration & dosage

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

Objective To verify the safety and efficacy of IONTRIS particle therapy system ( IONTRIS) in clinical implementation. Methods Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial:31 males and 4 females with a median age of 69 yrs ( range 39?80) . Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non?metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results Twenty?two patients received carbon ion and 13 had proton irradiation. With a median follow?up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression?free survival rate was 93.8％ (15/16). Among the 19 patients with prostate cancer, biological?recurrence free survival was 100％. Particle therapy was well tolerated in all 35 patients. Twenty?five patients (71.4％) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow?up. Six ( 17.1％) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow?up is needed to observe the late toxicity and long term result.

Objective To verify the safety and efficacy of IONTRIS particle therapy system ( IONTRIS) in clinical implementation. Methods Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial:31 males and 4 females with a median age of 69 yrs ( range 39?80) . Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non?metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results Twenty?two patients received carbon ion and 13 had proton irradiation. With a median follow?up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression?free survival rate was 93.8％ (15/16). Among the 19 patients with prostate cancer, biological?recurrence free survival was 100％. Particle therapy was well tolerated in all 35 patients. Twenty?five patients (71.4％) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow?up. Six ( 17.1％) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow?up is needed to observe the late toxicity and long term result.