This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

Objective To observe the clinical efficacy of thumb-tack needling for subcutaeous embedding combined with joint mobilization in the treatment of post-stroke shoulder-hand syndrome.Methods A total of 80 patients with post-stroke shoulder-hand syndrome were randomly divided into a treatment group and a control group,with 40 patients in each group.Both groups were given arthrocentesis,the control group was given ordinary acupuncture on the basis of arthrocentesis,and the treatment group was combined with thumb-tack needling for subcutaeous embedding.One course of treatment was 4 weeks and a total of 4 weeks of treatment was given.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes of Visual Analogue Scale(VAS)of pain scores and simplified Fugl-Meyer Assessment(FMA)scores,as well as the pain-free passive forward flexion and abduction of the shoulder joint of the affected limb were observed before and after treatment.The Simple Quality of Life Scale(SF-36)scores of the patients in the two groups were compared after treatment.The safety and the occurrence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 95.00%(38/40)in the treatment group and 80.00%(32/40)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the VAS scores and upper extremity FMA scores of the patients in the two groups were significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving the VAS scores and upper extremity FMA scores,and the differences were statistically significant(P＜0.05).(3)After treatment,the joint mobility of patients in the two groups were significantly improved(P＜0.05),and the improvement of shoulder joint movement in the treatment group was superior to that in the control group,and the difference was statistically significant(P＜0.05).(4)After treatment,the SF-36 Quality of Life Scale scores of the treatment group were significantly superior to those of the control group in terms of physical function,psychological function,emotional health,and social function levels,and the difference was statistically significant(P＜0.05).(5)There was no significant difference in the incidence of adverse reactions between the treatment group and the control group(P＞0.05).Conclusion Thumb-tack needling for subcutaeous embedding combined with joint mobilization exert certain effect in the treatment of post-stroke shoulder-hand syndrome.It can significantly improve the pain symptoms of patients,thus improving their quality of life,and the clinical effect is remarkable.

BACKGROUND:Sepsis-induced systemic inflammation leads to rapid bone mass loss;however,there is a lack of effective treatments.Ulinastatin is an anti-inflammatory drug,but its protective effect and mechanism on bone under sepsis-induced systemic inflammation are still unclear. OBJECTIVE:To explore whether ulinastatin can relieve acute bone loss caused by lipopolysaccharide. METHODS:(1)Animal experiment.Thirty male C57BL/6 mice were randomly divided into three groups(n=10 per group):control group,model group and experimental group.The control group was injected intraperitoneally with normal saline,the model group was injected intraperitoneally with lipopolysaccharide,and the experimental group was injected intraperitoneally with lipopolysaccharide and ulinastatin.In the experimental group,ulinastatin was injected continuously for 3 days.After intraperitoneal injection of ulinastatin for 14 days,femoral tissues were taken for CT scanning and pathological observation.(2)Cell experiment.C57BL/6 mouse primary osteoblasts were isolated and divided into three groups:the control group was routinely cultured,lipopolysaccharide was added to the model group,and lipopolysaccharide with ulinastatin was added to the experimental group.Cell proliferation and osteogenic differentiation were detected.C57BL/6 mouse bone marrow mononuclear cells were isolated and divided into three groups:the control group was routinely cultured,lipopolysaccharide was added to the model group,and lipopolysaccharide and ulinastatin were added to the experimental group.Osteoclast differentiation was detected. RESULTS AND CONCLUSION:(1)Animal experiment.CT scanning and hematoxylin-eosin staining showed that bone mass in lipopolysaccharide-treated mice was reduced but increased after treatment with ulinastatin.Tartrate resistant acid phosphatase staining showed that the number of osteoclasts in bone tissue increased in the model group,but significantly decreased in the experimental group compared with the model group.(2)Cell experiment.Cell counting kit-8 assay showed that lipopolysaccharide treatment inhibited the proliferation of osteoblasts,and ulinastatin elevated the proliferation of osteoblasts after lipopolysaccharide treatment.Alkaline phosphatase staining,alizarin red staining and osteogenesis-related gene(alkaline phosphatase,Runx2,osteocalcin,osteoblastin,nuclear factor κB receptor-activating factor ligand,osteoprotegerin)detection showed that lipopolysaccharide treatment inhibited osteogenic differentiation of osteoblasts and elevated the nuclear factor κB receptor-activating factor ligand/osteoprotegerin ratio;ulinastatin did not have any significant effect on the reduction of osteoblast function induced by lipopolysaccharide but decreased the nuclear factor κB receptor-activating factor ligand/osteoprotegerin ratio.Tartrate resistant acid phosphatase staining and osteoclast-related gene(tartrate resistant acid phosphatase and matrix metalloproteinase 9)detection showed that lipopolysaccharide treatment could promote osteoclast differentiation of bone marrow monocytes,while ulinastatin could inhibit lipopolysaccharide-induced osteoclast differentiation of bone marrow monocytes.(3)Overall,ulinastatin can significantly inhibit lipopolysaccharide-induced bone loss,mainly through promoting osteoblast proliferation and directly or indirectly inhibiting osteoclast differentiation to alleviate bone loss and achieve osteoprotective effects.

Objective To observe the effects of matrine on the proliferation,migration,and invasion of human neuroblastoma cells,and to investigate its potential mechanism.Methods This study was divided into AS experimental group(SK-N-AS cells treated with IC50 concentration of matrine),AS blank group(SK-N-AS cells cultured under normal conditions),AS control group(SK-N-AS cells treated with an equal amount of dimethyl sulfoxide),DZ experimental group(SK-N-DZ cells treated with IC50 concentration of matrine),DZ blank group(SK-N-DZ cells cultured under normal conditions),and DZ control group(SK-N-DZ cells treated with an equal amount of dimethyl sulfoxide).Scratch assay and Transwell chamber were used to measure the effect of matrine on the migration and invasion.The expression of E-cadherin,N-cadherin and Vimentin were tested by Western blot.Results After different intervention,the migration percentages of AS blank group,AS control group,AS experimental group,DZ blank group,DZ control group and DZ experimental group were(66.32±3.12)％,(65.27±3.44)％,(23.73±0.79)％,(46.25±4.68)％,(44.15±5.60)％and(16.77±3.52)％,respectively;the number of invasive cells were 870.45±19.32,865.32±23.39,492.74±16.81,1 198.10±43.71,1 203.03±71.91 and 891.69±42.62,respectively;the expression levels of E-cadherin protein were(100.00±11.72)％,(105.65±13.11)％,(477.20±29.71)％,(100.00±12.54)％,(97.78±12.77)％and(240.53±12.23)％,respectively;the expression levels of N-cadherin protein were(100.00±15.44)％,(103.90±10.76)％,(43.52±9.96)％,(100.00±10.12)％,(104.95±10.49)％and(38.39±8.70)％,respectively;Vimentin protein expression levels were(100.00±9.51)％,(97.39±11.33)％,(59.13±10.25)％,(100.00±13.20)％,(96.27±11.01)％and(47.67±9.48)％,respectively.There were statistically significant differences in the above indexes between the AS group and the AS blank group(P＜0.01,P＜0.001),and there were statistically significant differences between the above indexes in the DZ group and the DZ blank group(P＜0.01,P＜0.001).Conclusion Matrine inhibits the proliferation,migration,and invasion of neuroblastoma SK-N-AS and SK-N-DZ cells,potentially through suppressing epithelial-mesenchymal transition.

Objective:To explore the differences in tumor-specific growth factors, cellular immune function and efficacy of olaparib and platinum-containing regimen for treatment of platinum-sensitive relapsed ovarian cancer patients with BRCA mutation.Methods:A retrospective cohort study was conducted. A total of 100 platinum-sensitive relapsed BRCA-mutant ovarian cancer patients in Baoding Second Central Hospital from September 2017 to March 2020 were retrospectively selected. The clinical data of the patients were analyzed, and they were divided into the olaparib group (treated with olaparib tablets) and the platinum-containing regimen group (treated with paclitaxel and platinum drugs for 6 cycles, followed by olaparib tablets maintenance therapy), with 50 patients in each group. The clinical efficacy, tumor specific growth factor [carbohydrate antigen (CA) 125, CA199, human epididymal protein 4 (HE4)] levels, cellular immune function-related indicators [T-cell subsets (proportions of CD3 + cells and CD4 + cells), CD4 + cells/CD8 + cells ratio (CD4 +/CD8 +)], and quality of life scores before treatment and after 2, 4 and 6 cycles of treatment of the two groups were compared, as well as the safety of the two groups. The data of three years of follow-up were obtained, Kaplan-Meier method was used to analyze the progression-free survival (PFS) of patients in the two groups, and log-rank test was used for comparison between groups. Results:The age of patients in the olaparib and platinum-containing regimen groups was (53±7) years old and (56±7) years old, respectively. The differences in compositions of patients with different age, body mass index, Eastern Cooperative Oncology Group (ECOG) performance status score, primary tumor location, lesion size, pathological stage, pathological type, germline BRCA mutation, and previous chemotherapy response between the two groups were not statistically significant (all P > 0.05). The objective response rate (ORR) [58.0% (29/50) vs. 38.0% (19/50)] and disease control rate (DCR) [80.0% (40/50) vs. 56.0% (28/50)] of the olaparib group after treatment were higher than those of the platinum-containing regimen group, and the differences were statistically significant (both P < 0.05). Serum CA125, CA199 and HE4 levels were gradually decreased in both groups before treatment and after 2, 4 and 6 cycles of treatment (all P < 0.05); serum CA125, CA199 and HE4 levels in the olaparib group after 2, 4 and 6 cycles of treatment were lower than those in the platinum-containing regimen group, and the differences were statistically significant (all P < 0.05). The CD3 + cells ratio, CD4 + cell ratio and CD4 +/CD8 + in the olaparib group gradually increased before treatment and after 2, 4 and 6 cycles of treatment (all P < 0.05), while those in the platinum-containing regimen group all gradually decreased (all P < 0.05); the CD3 + cells ratio, CD4 + cells ratio and CD4 +/CD8 + in the olaparib group were higher than those in the platinum-containing regimen group after 2, 4 and 6 cycles of treatment, and the differences were statistically significant (all P < 0.05). The quality of life scores of both groups increased before treatment and after 2, 4 and 6 cycles of treatment (all P < 0.05), and the quality of life scores of the olaparib group were higher than those of the platinum-containing regimen group after 2, 4 and 6 cycles of treatment, and the differences were statistically significant (all P < 0.05). The incidence of nausea, fatigue and malaise, vomiting, anemia, and diarrhea at all levels in the olaparib group was lower than those in the platinum-containing regimen group (all P < 0.05). By follow-up for 3 years, there was no statistically significant difference in PFS between the olaparib group and the platinum-containing regimen group ( P > 0.05). Conclusions:The efficacy of olaparib treatment in platinum-sensitive relapsed ovarian cancer patients with BRCA mutation is superior to platinum-containing regimen, and it can increase the level of T cells, inhibit the expression of tumor-specific growth factors, improve the quality of life, and have a positive effect on improving the safety of treatment.

Objective:To explore the impact of uncertain resection on postoperative survival in non-small cell lung cancer.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on the data of 477 patients with non-small cell lung cancer who underwent lobectomy in the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from December 2012 to December 2013. There were 302 males and 175 females, aged (59±8) years (range: 27 to 79 years). According to the surgical resection criteria issued by the International Association for the Study of Lung Cancer, the patients were divided into the intact resection group (R0 group, 286 cases) and the uncertain resection group (R (un) group, 191 cases). Clinical data between the two groups were compared using χ2 test, and propensity score matching (PSM) was performed on patients using the R language, with matching variables including gender, age, smoking history, adjuvant therapy, TNM stage, pathological type, and tumor site. The nearest-neighbor method was used for 1∶3 matching and the caliper value was 0.02. The survival curve was plotted using the Kaplan-Meier method and compared using the Log-rank test. The Cox proportional hazards regression model was used to identify risk factors in overall survival (OS). Subgroup analysis was based on TNM staging and mediastinal lymph node metastasis status. Results:In the R (un) group, 68 patients had positive lymph in the highest group and 129 patients did not undergo complete dissection of the mediastinal lymph nodes. The baseline data for the R0 group and the R (un) group were corrected using PSM, and a total of 369 patients were successfully matched, including 227 cases in the R0 group and 142 cases in the R (un) group. After PSM, the 5-year survival rates of the R0 group and the R (un) group were 64.3% and 52.1%, respectively ( P=0.021). The 5-year survival rates of stage Ⅰ, Ⅱ, and Ⅲ patients were 85.2%, 65.9%, and 34.8%, respectively ( P<0.01). TNM stage ( χ2=46.913, P<0.01), pathological classification of adenosquamous cell carcinoma ( HR=5.970, 95% CI: 3.117 to 11.431, P<0.01) and R (un) resection ( HR=1.512, 95% CI: 1.065 to 2.147, P=0.021) were prognostic factors for postoperative survival. Subgroup analysis showed that in stage Ⅲ patients, 5-year survival rates of the R0 group and the R (un) group after resection were 45.8% and 9.5%, respectively ( P=0.002). Among patients with mediastinal lymph node metastasis, 5-year survival rates of the R0 group and the R (un) group were 50.6% and 7.1%, respectively ( P<0.01). Conclusions:TNM staging, pathological type, and R (un) resection are prognostic factors for overall postoperative survival in non-small cell lung cancer. In stage Ⅰ and Ⅱ patients, R (un) is not a prognostic factor for postoperative survival of non-small cell lung cancer. In patients with stage Ⅲ and mediastinal lymph node metastasis, R (un) is a prognostic factor for non-small cell lung cancer after surgery.

Objective:To explore the clinical manifestations and genetic basis for a Chinese pedigree affected with atypical Charcot-Marie-Tooth disease type 1 A (CMT1A).Methods:A patient admitted to the Department of Neurology, Xijing Hospital Affiliated to Air Force Medical University in June 2022 was selected as the study subject. Clinical data of the patient was collected, and 17 family members from four generations of this pedigree were traced based on pes arcuatus and atypical clinical symptoms. Neuroultrasound and genetic testing were carried out on available family members. Whole exome sequencing and multiple ligation-dependent probe amplification assay were carried out for the proband and some of the affected members of the pedigree.Results:The proband, a 15-year-old male, had presented with paroxystic limb pain with weakness, accompanied by pes cavus and hypertrophy of gastrocnemius muscles, without stork leg sign caused by muscles atrophy in the distal lower extremities. MRI has revealed no sign of fat infiltration in the muscles of both legs. Nerve conduction examination had indicated damages of the sensory and motor nerves of the limbs, mainly with demyelinating changes. Seven members of the pedigree had pes arcuatus, including 5 presenting with paroxysmal neuropathic pain and myasthenia in the limbs, whilst 2 were without any clinical symptoms. Neurosonography of the proband, his brother, father and aunt showed thickened peripheral nerves of the extremities with unclear bundle structure. Genetic analysis revealed a large repeat encompassing exons 1 to 5 of the PMP22 gene and flanking regions (chr17: 15133768_15502298) in some of the affected members, which was predicted to be pathogenic. Conclusion:The duplication of PMP22 gene was considered to be pathogenic for this CMT1A pedigree.

Objective To analyze the incidence and risk factors of hypothermia in elderly patients with malnutrition during proximal femoral nail antirotation(PFNA)internal fixation under general anesthesia.Methods A total of 139 elderly patients underwent PFNA internal fixation under general anesthesia were selected,and the nutritional status scores 1 day before surgery ranged from 0 to 11 points.Univariate and multivariate Logistic binary regression analysis was performed to analyze the related factors that may lead to intraoperative hypothermia.Results Among 139 elderly patients with preoperative nutritional scores of 0 to 11 points,79 cases(56.83%)developed intraoperative hypothermia.The results of univariate and multivariate Logistic binary regression analysis suggested that age≥75 years old,mini nutritional assessment short form(MNA-SF)nutritional score 0 to 7 points,BMI<18.5 kg/m2,duration of general anesthesia≥2 hours,intraoperative flushing fluid volume≥1 000 mL and intraoperative fluid volume≥1 000 mL were the risk factors for the occurrence of intraoperative hypothermia in elderly patients(OR>1,P<0.05).The use of warm blanket insulation was the protective factor against the occurrence of intraoperative hypothermia(OR<1,P<0.05).Conclusion The incidence of intraoperative hypothermia during PFNA internal fixation under general anesthesia in elderly patients with mainutrition before operation is high,and patients with poor nutritional status are more likely to develop intraoperative hypothermia.Patients with older age,poor nutritional status,lower BMI,longer duration of general anesthesia,and more intraoperative flushing fluid volume and intraoperative fluid volume are likely to lead to intraoperative hypothermia.The use of warm blanket can reduce the incidence of intraoperative hypothermia.

AIM:To perform a multidimensional analysis of the clinical study characteristics of endo-metriosis based on the ClinicalTrials.gov,providing comprehensive and objective information for re-searchers,clinicians,and clinical pharmacists.METHODS:A thorough investigation was conduct-ed on clinical trials related to endometriosis,regis-tered on the ClinicalTrials.gov from its inception to October 20,2023.Relevant trial data were extract-ed and statistically analyzed using bibliometrics and comparative research methods.RESULTS:A to-tal of 667 endometriosis clinical studies were regis-tered globally,showing an annual increase.The United States(127 trials),France(70 trials),and Ita-ly(57 trials)had the highest number of registered trials.Interventional studies were predominant(416 trials,62.4%),followed by observational stud-ies(251 trials,37.6%).Within interventional stud-ies,drug therapy was the primary intervention(223 trials,53.6%).Despite endometriosis being a female condition,male subjects were also consid-ered,with 6 trials specifically requiring male partici-pants and 37 trials not restricting gender.Compa-nies/corporations were the main funding sources,while public and governmental organizations pro-vided relatively less funding.CONCLUSION:Clinical trial research on endometriosis is in a phase of growth,with drug therapy being the main treat-ment approach.However,there is a relative lack of investment and attention from public funds and governmental organizations.

Objective:To establish an in vivo infection model of West Nile virus (WNV) pseudovirus and evaluate the neutralizing activity of antibody WNV-XH1.Methods:A stable cell line that can package the WNV pseudovirus was established in the early stage to prepare the pseudovirus supernatant. The supernatant was concentrated and infected BHK21 cells to detect the titer of the pseudovirus. After intraperitoneal injection of the pseudovirus into C57BL/J mice, bioluminescence imaging was performed to observe the infection status of the pseudovirus in the mice. After simultaneous infection, blood was collected and ELISA was used to detect NS1 levels in mouse serum. The in vivo functional activity of antibody WNV-XH1 was evaluated using the established mouse infection model.Results:Fluorescence was detected in C57BL/J mice infected with WNV pseudovirus, and the NS1 levels in the peripheral blood serum of mice infected with pseudovirus were significantly higher than those of non infected mice (1.453±0.09vs0.305±0.018). After intravenous administration of WNV-XH1 antibody before the attack, the fluorescence signal in the mice decreased and the serum NS1 level decreased (0.384±0.015).Conclusions:A successful in vivo infection model of WNV pseudovirus was established, and it was confirmed that the antibody WNV-XH1 had a protective effect against WNV pseudovirus infection in vivo.