Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans ; Male ; Infertility, Male/genetics* ; Adult ; Micronucleus Tests ; Semen Analysis ; Oligospermia/genetics* ; Azoospermia/genetics* ; Chromosome Aberrations ; Sperm Count ; Micronuclei, Chromosome-Defective ; Middle Aged

Image 1.

As an indispensable trace element in the human body,copper plays an important role in various physiological and biochemical reactions.The dyshomeostasis of copper leads to the disorder of copper metabolism and the occurrence of related diseases.Cuproptosis,a newly proposed regulatory cell death mode,is different from the known apoptosis,pyroptosis,necroptosis,and ferroptosis.Recent studies have found that the dyshomeostasis of copper has been observed in a variety of cancers.Therefore,targeting copper for disease treatment may become a new strategy and a new idea.This article systematically summarizes the fundamental properties of copper,copper dyshomeostasis-related diseases (Menkes syndrome,Wilson's disease,and cancer) and their treatment,and reviews the research progress in cuproptosis.
Humans ; Copper/metabolism* ; Homeostasis ; Neoplasms/metabolism* ; Hepatolenticular Degeneration/metabolism* ; Menkes Kinky Hair Syndrome/metabolism*

Objective This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression (n = 113,154) and MDD (n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.

Objective To study the relationship between the changes of sagittal spinopelvic parameters and facet joint-derived low back pain in patients with hip osteoarthritis after hip arthroplasty.Methods The clinical data of 30 patients with facet joint-derived low back pain induced by hip osteoarthritis who underwent unilateral hip arthroplasty(observation group)from June 2019 to November 2020 in our hospital were retrospectively analyzed,and 50 healthy subjects who underwent lumbar X-ray examination in the physical examination center of our hospital at the same time were randomly selected as the control group.The sagittal spinopelvic parameters were measured based on the X-ray,including pelvic incidence(PI),pelvic tilt(PT),sacral slope(SS),lumbar lordosis(LL),sacrum pubic incidence(SPI)and sacrum pubic posterior angle(SPPA).The correlation between the changes of sagittal spinopelvic parameters and facet joint-derived low back pain was analyzed by multiple linear regression,and its diagnostic efficacy to facet joint-derived low back pain was analyzed by receiver operating characteristic(ROC)curve.Results The PI,LL,SPI or SPA before and 1 year after surgery of the observation group had no significant difference combined with those of the control group(P>0.05).The PT before surgery of the observation group was smaller than that of the control group(P<0.05),and the SS before surgery was larger than that of the control group(P<0.05).Multiple linear regression analysis showed that PT and SS before surgery were correlated with facet joint-derived low back pain(P<0.05).The sensitivity of PT and SS before surgery in diagnosing facet joint-derived low back pain were 50.00%and 73.30%,with the specificity of 88.00%and 78.00%,respectively.ROC curve analysis showed that the area under the curve of PT and SS before surgery in diagnosing facet joint-derived low back pain were 0.708(95%CI:0.595 to 0.822)and 0.775(95%CI:0.673 to 0.877),respectively.Conclusion Patients with hip osteoarthritis pain have significantly larger SS and significantly smaller PT.Hip arthroplasty can alleviate the symptoms of low back pain without affecting the sagittal spinopelvic balance;the PT and SS before surgery are correlated with the facet joint-derived low back pain,and they are of high value in the diagnosing facet joint-derived low back pain.

Objective To observe the effect of electric stimulation on nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3)signaling pathway and microglial cell morphology in mice with lipopolysaccharide(LPS)induced chronic neuroinflammation,and to explore the protective mechanism of electric stimulation on brain of mice.Methods C57BL/6 mice were randomly divided into blank control group(n=8),model group(n=12),sham electroacupuncture group(n=6)and electroacupuncture group(n=6).Except blank control group,mice in other groups were injected intraperitoneally with LPS(0.25 mg/kg)for 7 consecutive days.On the 8th day,mice in the sham electroacupuncture group and electroacupuncture group were treated with acupuncture or Zusanli electroacupuncture for 7 consecutive days.The mice were weighed before the experiment,on the 7th and 14th days.On the 13th day,the elevated cross maze test was performed on the mice.The open field test was performed on the 14th day.After the experiment,immunofluorescence assay was used to determine the expression of microglial ionized calcium binding adaptor molecule-1(Iba-1)in prefrontal cortex region.The mRNA expression of NF-κB,inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),Caspase-1 and interleukin(IL)-18 were detected by Real-time PCR.The protein expression levels of NF-κB,iNOS,NLRP3,apoptosis-associated speck-like protein containing a CARD(ASC),Caspase-1,IL-1βand IL-18 were detected by Western blotting.Results Weight change,On the 7th day,compared with the control group,the body weight of mice in model group,sham electroacupuncture group and electroacupuncture group decreased(P＜0.0001),respectively;On the 14th day,compared with the control group,the weight of mice in the model group decreased(P＜0.0001);Compared with the sham electroacupuncture group,the body weight of mice in the electroacupuncture group increased(P＜0.05).Elevated cross maze experiment,compared with the control group,the total distance and open arm retention time of mice in model group decreased,while the closed arm retention time increased(P＜0.05).The open field experiment showed that compared with the control group,the model group mice showed a decrease in total distance traveled,slower movement speed,and fewer entries into the central area(P＜0.001);Compared with the model group,the electroacupuncture group showed an increase in all three indicators(P＜0.01);Compared with the sham electroacupuncture group,the total distance and motion speed of mice in electroacupuncture group both increased(P＜0.05).Immunofluorescence assay,compared with the control group,the relative fluorescence of Iba-1 in prefrontal cortex area of mice in model group increased(P＜0.05).Compared with the model and sham electroacupuncture group,the relative fluorescence of Iba-1 in prefrontal cortex area of mice in electroacupuncture group decreased(P＜0.05).Real-time PCR showed that compared with the control group,mRNA expressions of NF-κB,iNOS,TNF-α,Caspase-1 and IL-18 in the model group increased(P＜0.05);Compared with the model group,mRNA expressions of NF-κB,iNOS,TNF-α,Caspase-1 and IL-18 in electroacupuncture group decreased(P＜0.05).Western blotting indicated that compared with the control group,the protein expressions of NF-κB,iNOS,Caspase-1,IL-1β and IL-18 in model group increased(P＜0.05);Compared with model group,the protein expressions of NF-κB,iNOS,NLRP3,ASC,Caspase-1,IL-1β and IL-18 in electroacupuncture group decreased(P＜0.05);Compared with the sham electroacupuncture group,IL-18 protein in electroacupuncture group decreased(P＜0.05).Conclusion Electroacupuncture can improve the behavioral performance of mice and inhibit the activation of microglia in the cortical region of mice,which may play an anti-inflammatory and protective role by regulating NF-κB/NLRP3 pathway.

Humans ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Hydrazines/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy*

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*