Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Objective:To explore the effects of intraspinal blocking analgesia on the delivery quality and puerperal pelvic floor function of primiparas.Methods:A total of 99 primiparas who delivered in the Second People′s Hospital of Wuhu City from January 2021 to April 2022 were enrolled in this study, 54 patients received intraspinal blocking analgesia (study group) and 45 patients received conventional treatment, without intraspinal blocking analgesia (control group). The delivery quality between the two groups was compared, and the pelvic floor function was evaluated and compared by pelvic floor rehabilitation therapy instrument and pelvic floor ultrasound at 6-8 weeks after delivery.Results:Vaginal delivery were successful in both groups. The total labor duration in the study group was longer than that in the control group: (8.03 ± 2.94) h vs. (6.89 ± 3.49) h, there was statistical difference ( P<0.05). The maximum value of pelvic floor rapid contraction stage, rising time and average value of continuous contraction stage in the study group were higher than those in the control group: (32.85 ± 10.13) μV vs. (14.73 ± 3.25) μV, (0.28 ± 0.06) s vs. (0.22 ± 0.05) s, (30.26 ± 5.24) μV vs. (16.74 ± 4.00) μV, there were statistical differences ( P<0.05). There were no statistical differences in other indicators such as the pre-resting stage, rapid contraction phase recovery time and post-resting stage between the two groups ( P>0.05). The rate of pelvic floor class Ⅰ and class Ⅱ muscle abnormalities at 6-8 weeks after delivery in the study group were lower than those in the control group, but there were no statistical differences ( P>0.05). The maximum Valsalva state hiatus area of levator ani muscle, maximum Valsalva state bladder posterior urethral angle, hiatus area of levator ani muscle at rest state and bladder neck degree in the study group were smaller than those in the control group: (19.09 ± 4.82) cm 2 vs. (23.00 ± 5.34) cm 2, (138.59 ± 23.14)° vs. (148.47 ± 20.38)°, (9.96 ± 2.63) cm 2 vs. (11.60 ± 2.75) cm 2, (20.13 ± 4.37) mm vs. (28.05 ± 6.52) mm, there were statistical differences ( P<0.05). Conclusions:Although intraspinal block analgesia can prolong the total labor time of primipara, but it can reduce the damage of pelvic floor function, possibly by increasing systolic period to protect pelvic floor muscles.

Objective:This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma.Methods:The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) .Results:Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration ( P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups ( P>0.05), and the median PFS and OS time were not reached ( P>0.05) . Conclusions:In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

Objective:To learn about the operation of arsenic reduction and water improvement projects and the present situation of arsenic level in drinking water in drinking water type endemic arsenic poisoning areas in Jinzhong City, Shanxi Province.Methods:From May to August 2023, in accordance with the requirements of the "Investigation Plan for Arsenic Content in Drinking Water of Residents in Arsenic Exposed Areas of Shanxi Province", 29 high arsenic villages in the drinking water type endemic arsenic poisoning historical areas of Pingyao County, Jiexiu City and Qi County in Jinzhong City, Shanxi Province were selected as monitoring villages to investigate the operation of water improvement projects. The drinking water samples of village residents were collected and water arsenic level was measured by hydride atomic fluorescence spectrophotometry. At the same time, monitoring of the operation of water improvement projects and water arsenic level for residents within adjacent local areas were carried out in townships where 29 high arsenic villages located.Results:In 2023, a total of 29 high arsenic villages in 3 counties (cities) of Jinzhong City, Shanxi Province were monitored, all of which had undergone water improvement and all water improvement projects were operating normally. The range of water arsenic level was 0.000 - 0.047 mg/L, with 27 high arsenic villages had water arsenic level < 0.01 mg/L. A total of 81 natural villages within the adjacent local areas of high arsenic villages in Jinzhong City were monitored, all of which had undergone water improvement and the water improvement projects were operating normally. The range of water arsenic level was 0.000 - 0.043 mg/L, and there were 4, 7, and 2 natural villages in Pingyao County, Jiexiu City and Qi County with water arsenic level ranging from 0.01 to 0.05 mg/L.Conclusions:All high arsenic villages in Jinzhong City, Shanxi Province have completed water improvement, and the water improvement projects are operating normally. The water arsenic level in most high arsenic villages meets the national drinking water standard (< 0.01 mg/L).

Objective:To analyze the review results of salt iodine monitoring in the county-level laboratories of iodine deficiency disorders in Jinzhong City, and to learn about the quality of the monitoring in the county-level laboratories, so as to provide scientific basis for formulating iodine deficiency disorders prevention and control strategies.Methods:From 2021 to 2023, Jinzhong Center for Disease Control and Prevention used the systematic random sampling method to select 5% (15 samples each) of all edible salt samples (short for salt samples) tested by 11 county-level iodine deficiency disorders laboratories under its jurisdiction for retesting each year. The salt iodine was determined by the redox titration method in accordance with the "General Test Method in Salt Industry-Determination of Iodine" (GB/T 13025.7-2012). Comparisons between groups for count data were analyzed using the χ 2 test, and the comparisons between groups for measurement data were analyzed using a random group design t-test. Results:From 2021 to 2023, the municipal laboratories reviewed and tested 165 salt samples (495 in total over 3 years). The proportion of households using adquately iodized salt tested by county-level laboratories was 92.53% (458/495), with annual rates of 89.70% (148/165), 93.33% (154/165), and 94.55% (156/165), respectively. The proportion of households using adquately iodized salt detected by municipal laboratories was 94.95% (470/495), with annual rates of 90.91% (150/165), 96.36% (159/165), and 97.58% (161/165), respectively. There was no significant difference in the proportion of households using adquately iodized salt detected by the two-level laboratories from 2021 to 2023 (χ 2 = 2.48, P = 0.116). The proportion of salt samples with relative error > 20% in the salt iodine detection results of county-level laboratories reviewed at the municipal laboratory from 2021 to 2023 were 20.00% (33/165), 16.97% (28/165), and 8.48% (14/165), respectively. The differences between different years were statistically significant (χ 2 = 8.49, P = 0.004). Compared with 2023, in 2021 and 2022, the differences were statistically significant ( P < 0.05). The proportion of salt samples with relative error > 30% were 7.88% (13/165), 6.06% (10/165), and 3.64% (6/165), respectively. There was no significant difference among different years (χ 2 = 2.69, P = 0.101). The comparison of laboratory test results between the two-level laboratories showed statistically significant differences ( t = 6.05, P < 0.001). Among the group data reviewed, there were a total of 16 groups with statistical significance, including 4 groups in 2021, 7 groups in 2022, and 5 groups in 2023. Conclusions:The review results indicate that the quality of salt iodine monitoring in county-level laboratories in Jinzhong City continues to improve, and the testing data are authentic and reliable. In the future, training for county-level laboratory inspectors should be increased to enhance their operational skills and minimize testing result errors.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Nonketotic hyperglycinemia(NKH), also known as glycine encephalopathy, is a rare and life-threatening autosomal recessive disease.Due to the insufficient activity of the glycine cleavage enzyme system(GCS), glycine can not be degraded and accumulates in the body.It leads to progressive damage to the nervous system.The clinical manifestations of the disease vary.Based on ultimate outcome, NKH is categorized into severe NKH and attenuated NKH.It is characterized by increased glycine level in cerebrospinal, and further confirmatory tests are molecular genetic testing and enzymatic testing.So far, no causal treatment of NKH has been discovered and the overall prognosis is still poor.The therapy is based on sodium benzoate and N-methyl-D-aspartate(NMDA)receptor site antagonists.This article reviews the progress of NKH, in order to help clinicians comprehensively identify NKH and take proactive measures to get the best results.

Community acquired pneumonia(CAP)has a high morbidity and mortality rate, and can bring a heavy social and economic burden.Its etiology is complex.How to identify high-risk children, early diagnosis, prognosis prediction are the focus of clinical research.Early identification and active intervention of high-risk children who need hospitalization or admission to pediatric intensive care unit by using score scales and biomarkers are crucial to improve the survival rate.This review summarized the assessment of severity and prognosis of CAP in children by different score scales and biomarkers.

Objective:This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) .Methods:The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed.Results:Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) .Conclusions:Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.