OBJECTIVE To compare the efficacy， safety， and cost-effectiveness of two different formulations of short-acting recombinant human growth hormone （rhGH） in the treatment of patients with short stature. METHODS Data from patients with short stature treated with short-acting rhGH at the Leshan People’s Hospital from August 2016 to June 2023 were collected. Patients were divided into powder formulation group and aqueous formulation group based on the rhGH formulation used. The changes in growth-related efficacy indicators and the occurrence of adverse drug reactions were compared between two groups after 12 months of treatment； cost-effectiveness analysis and sensitivity analysis were used to compare the cost per unit of effect achieved； subgroup analysis was performed by dividing the patients into growth hormone deficiency （GHD） subgroup and idiopathic short stature （ISS） subgroup based on clinical diagnosis. RESULTS After 12 months of treatment， the height and the levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in serum in aqueous formulation group and powder formulation group were significantly increased compared to before treatment （P＜0.001）， but there was no statistically significant difference in the changes of the above indicators between the two groups（P＞0.05）. The analysis results of GHD and ISS subgroups were consistent with the overall population. In the overall population， the cost-effectiveness ratio of powder formulation group （2 582 yuan/cm） was significantly better than that of aqueous formulation group （6 729 yuan/cm）， with a statistically significant difference （P＜0.001）， and the result was consistent in the GHD and ISS subgroups as well as in the sensitivity analysis. No serious adverse drug reactions occurred in either powder formulation or aqueous formulation group， and there was no statistically significant difference in the incidence of various adverse reactions between two groups （P＞0.05）. CONCLUSIONS Short-acting rhGH powder and aqueous formulations have equivalent efficacy and safety， but the powder formulation has greater economic advantages.

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Abstract: Objective To detect the polymorphisms of drug resistance-related genes pvcrt-o and pvmdr1 of Plasmodium vivax in lazan city in the China-Myanmar border, in order to guide the treatment plan of Plasmodium vivax. Methods A total of 48 Plasmodium vivax samples were collected from Lazan in the China-Myanmar border in 2007, and fragments of pvcrt-o and pvmdr1 genes were amplified by PCR and sequenced. The sequences were aligned with the Salvador I (Sal-I) strain reference genome sequences to determine the presence of SNPs. Results The target fragments of pvcrt-o gene were amplified from 39 Plasmodium vivax samples, while pvmdr1 genes were amplified from 40 samples. Amongst them, 25 samples had AAG insertion before the 10th amino acid (K10 insertion) of pvcrt-o gene, accounting for 64.1%. Non-synonymous mutations were detected at three loci of pvmdr1 gene (T958M, Y976F, and F1076L), the mutation rates were 100%, 22.5%, and 55.0%, respectively. There were three haplotypes of pvmdr1 gene, of which the triple mutant 958M/976F/1076L accounted for 22.5% (9/40), the double mutant 958M/Y976/1076L accounted for 32.5% (13/40), and the single mutant 958M/Y976/F1076 accounted for 45.0% (18/40). The proportion of strains with pvcrt-o and pvmdr1 gene mutation is 63.16%, which is significantly different from those only with pvmdr1 mutation. Conclusions The proportion of pvcrt-o and pvmdr1 gene mutation of 48 Plasmodium vivax isolates is high in the China-Myanmar border, and there is a certain degree of correlation between the two gene mutations. To assess changes in Plasmodium vivax drug resistance in this region, it is required to improve the surveillance of these two molecular markers.

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Aim To explore the effects of NaAsO

Objective To analyze the relationship between diurnal temperature range (DTR) and the hospitalization of stroke in Lanzhou,so as to provide a scientific basis for probing into the mechanism of temperature changes in inducing stroke and formulating comprehensive prevention and control measures for stroke by relevant departments.Methods The information of the patients hospitalized due to stroke in Lanzhou during January 2014 to December 2019 and the air pollutants (PM₁₀,SO₂,and NO₂) and meteorological data in the same period were collected for statistical analysis.Spearman rank correlation analysis was performed to analyze the correlations between air pollutants and meteorological factors.The distributed lag nonlinear model was adopted to fit the relationship between DTR and the number of stroke inpatients,and three-dimensional diagrams and the correlation diagrams of DTR against stroke risk were established.The stratified analysis was performed according to gender and age (< 65 years and ≥65 years).Results From 2014 to 2019,a total of 92 812 stroke patients were hospitalized in Lanzhou,with a male-to-female ratio of 1.35:1.There was a nonlinear relationship between DTR and the number of stroke inpatients in Lanzhou,which presented a lag effect.The low DTR at 4.5 ℃ had the largest RR value of 1.25 (95%CI=1.16-1.35) for stroke inpatients at a cumulative lag of 18 d.The effect of high DTR (18.5 ℃) on the hospitalization of stroke patients peaked at a cumulative lag of 21 d,with an RR value of 1.09 (95%CI=1.01-1.18).The stratified analysis results suggested that low levels of DTR had greater effects on the hospitalization of male stroke patients and stroke patients <65 years.Conclusions Short-term exposure to different levels of DTR had an impact on the number of stroke inpatients,and low levels of DTR had a slightly greater impact on stroke inpatients than high levels of DTR.Importance should be attached to the protection of males and people aged <65 years at low levels of DTR.
Humans ; Male ; Female ; Temperature ; Stroke ; Cold Temperature ; Hot Temperature ; Air Pollutants ; China/epidemiology*

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; CA-19-9 Antigen ; Cholangiocarcinoma/diagnosis* ; Female ; Humans ; Laparoscopy ; Lymphatic Metastasis ; Male ; Nomograms ; Prognosis ; Retrospective Studies

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

To analyze the collaborative use and separation reasons of lifting-thrusting and twirling reinforcing and reducing manipulation. Lifting-thrusting manipulation and twirling manipulation are two important contents of acupuncture methods. In traditional acupuncture and moxibustion, the two methods were used in reinforcing and reducing concert, which was mainly related to the therapeutic thought guided by the
Acupuncture Therapy ; Humans ; Lifting ; Moxibustion ; Needles ; Taiwan