ObjectiveTo investigate the effects of Zuoguiwan on osteoclast activation induced by breast cancer and its mechanism. MethodsTo simulate breast cancer-induced osteoclastic bone metastasis， RAW264.7 cells were cultured in conditioned medium containing 50% supernatant of MDA-MB-231 breast cancer cells. The dosages of Zuoguiwan used in the experiment were sera containing 5% and 10% Zuoguiwan. Tartrate-resistant acid phosphatase （TRAP） staining was used to detect osteoclast activation. Enzyme-linked immunosorbent assay （ELISA） was used to measure Cathepsin K secretion from RAW264.7 cells. Real-time quantitative polymerase chain reaction （PCR） was used to detect the mRNA expression levels of osteocalcin （OCN） and bone sialoprotein （BSP）. Immunoprecipitation was employed to detect the interaction between Runt-related transcription factor 2 （Runx2） and core binding factor β subunit （CBF-β）. Western blot was used to assess the protein expression of Runx2， phosphorylated Runx2 （p-Runx2）， extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， p38 mitogen-activated protein kinase （MAPK）， p-p38 MAPK， and CBF-β. ResultsCompared with the blank group， the MDA-MB-231 cell supernatant group showed a significant increase in TRAP-positive cell counts and Cathepsin K secretion. Meanwhile， the expression levels of p-Runx2， Runx2-CBF-β interaction， BSP and OCN mRNA， p-p38 MAPK， and p-ERK1/2 proteins were significantly decreased （P<0.01）. Compared with the MDA-MB-231 cell supernatant group， Zuoguiwan-containing sera significantly reduced TRAP-positive cell counts and Cathepsin K secretion （P<0.01）， significantly increased p-Runx2， BSP and OCN mRNA expression， as well as p-p38 MAPK and p-ERK1/2 protein levels， and promoted the interaction between Runx2 and CBF-β （P<0.01）. No significant change in Runx2 expression was observed. Compared to the blank group， the BVD-523 group showed significantly lower expression of p-p38 MAPK and p-ERK1/2 proteins （P<0.01）. Compared with the BVD-523 group， both low and high concentration Zuoguiwan-containing sera groups showed significantly higher p-p38 MAPK expression （P<0.01）， and the high concentration Zuoguiwan group also exhibited a significant increase in p-ERK1/2 expression （P<0.01）， while no statistical difference was found in the low-dose group. ConclusionZuoguiwan inhibits osteoclast activation by inducing phosphorylation of the key transcriptional regulator Runx2 in intra-osteoclast bone formation， and this process is closely associated with the activation of the p38 MAPK/ERK signaling pathway.

To understand the progress of, summarize the lessons learned from and analyze the challenges in the national schistosomiasis elimination program of China in 2024, this article presented the endemic situation of schistosomiasis and national schistosomiasis surveillance results in the People’s Republic of China in 2024. By the end of 2024, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to consolidate schistosomiasis elimination achievements, and 7 provinces of Jiangsu, Sichuan, Yunnan, Hubei, Hunan, Anhui and Jiangxi maintained the criteria of schistosomiasis transmission interruption. A total of 450 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2024, including 26 061 endemic villages covering 73 630 500 residents at risk of infections. Among the 450 counties (cities, districts) endemic for schistosomiasis, 388 (86.22%) achieved the criteria of schistosomiasis elimination and 62 (13.78%) achieved the criteria of transmission interruption. In 2024, a total of 4 102 624 individuals received immunological tests for schistosomiasis in China, with 44 823 sero-positives identified (1.09% seroprevalence), and a total of 169 722 individuals received parasitological examinations, with 1 egg-positives detected. A total of 27 321 cases with advanced schistosomiasis were documented in China by the end of 2024. In 2024, a total of 575 686 bovines were raised in schistosomiasis-endemic villages of China, and 113 842 bovines received immunological tests, with 235 sero-positives detected (0.21% seroprevalence), while no egg-positives were identified among the 167 475 bovines receiving parasitological examinations. In 2024, snail survey was performed covering an area of 680 498.27 hm² in China, and 190 778.66 hm² snail habitats were identified, including 59.09 hm² emerging snail habitats and 704.23 hm² reemerging snail habitats. In 2024, a total of 19 665 schistosomiasis patients receiving chemotherapy with praziquantel in China, and expanded chemotherapy was given to humans at 571 722 person-times and to bovines at 306 740 herd-times. In addition, snail control with chemical treatment covered 117 111.37 hm² snail habitats across China in 2024, and the actual area of chemical treatment was 66 562.95 hm², while environmental improvements were performed in snail habitats covering an area of 1 374.26 hm². The national schistosomiasis surveillance results showed that the mean prevalence rates of Schistosoma japonicum infections were both 0 among humans and bovines in China in 2024, and no S. japonicum infection was detected in snails. These data demonstrated that the prevalence of schistosomiasis remained at a low level in China in 2024; however, the areas of snail habitats remained high and the number of fenced cattle showed a slight increase. To address these risks, it is imperative to maintain the integrated strategy with an emphasis on management of the source of S. japonicum infection and intensified snail control in high-risk areas, and to reinforce schistosomiasis surveillance and forecast and snail control in high-risk areas.

Objective To systematically evaluate the risk factors for new-onset atrial fibrillation after off-pump coronary artery bypass grafting (OPCABG). Methods PubMed, EMbase, The Cochrane Library, CNKI, Wanfang, VIP, SinoMed were searched to collect published literature on risk factors for new-onset atrial fibrillation after OPCABG from inception to September 2022. Two authors independently screened, extracted data and evaluated the quality. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies, and Stata 12.0 and RevMan 5.4 softwares were used for meta-analysis. Results A total of 18 researches were included, including 6 354 patients of OPCABG. The NOS scores of the included studies were 6-8 points. Meta-analysis showed that age [MD=2.56, 95%CI (1.61, 3.52), P<0.001], hypertension [OR=1.77, 95%CI (1.18, 2.66), P<0.001], EuroSCORE Ⅱ score [MD=0.70, 95%CI (0.34, 1.06), P<0.001], frequent atrial premature beats or atrial tachycardia [OR=3.77, 95%CI (2.13, 6.68), P<0.001], left atrium diameter (LAD) [MD=1.64, 95%CI (0.26, 3.03), P=0.010], left ventricular ejection fraction (LVEF) [MD=−1.84, 95%CI (−2.85, −0.83), P<0.001], right coronary stenosis [OR=2.49, 95%CI (1.29, 4.81), P=0.006], three-vessel coronary artery lesions [OR=0.73, 95%CI (0.54, 0.97), P=0.030], not using β blockers [OR=0.81, 95%CI (0.69, 0.96), P=0.010], operation time [MD=10.13, 95%CI (8.15, 12.10), P<0.001], duration of mechanical ventilation [OR=2.85, 95%CI (1.79, 3.91), P<0.001] were risk factors for new-onset atrial fibrillation after OPCABG. Conclusion Advanced age, hypertension, high EuroSCOREⅡ score, frequent atrial premature beats or atrial tachycardia, increased LAD, decreased LVEF, right coronary stenosis, three-vessel coronary artery lesions, not using β blockers, prolonged operation time and mechanical ventilation are risk factors for new-onset atrial fibrillation after OPCABG. Due to factors such as the methodology, content and quality of the included literature, the conclusion of this study need to be supported by more high-quality studies.

Objective To screen differentially expressed long non-coding RNAs (lncRNAs) in the liver of mice infected with Schistosoma japonicum during the chronic pathogenic stage and identify their functions, so as to provide insights into unravelling the role of lncRNAs in S. japonicum infection-induced liver disorders. Methods Twenty 6-week-old C57BL/6 mice were randomly divided into two groups, of 10 animals each group. Each mouse in the experimental group was infected with (15 ± 2) S. japonicum cercariae via the abdomen for modeling chronic S. japonicum infection in mice, and distilled water served as controls. All mice were sacrificed 70 days post-infection, and mouse liver specimens were sampled for RNA extraction and library construction. All libraries were sequenced on the Illumina NovaSeq 6000 sequencing platform. Data cleaning was performed using the fastp software, and reference genome alignment and gene expression (FPKM) calculation were performed using the HISAT2 software. Potential lncRNA sequences were predicted using the software CNIC, CPC, Pfam, and PLEK, and potential lncRNAs were screened. Differentially expressed lncRNAs were screened with the DESeq2 software and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to identify biological processes and metabolic pathways involved in target genes of differentially expressed lncRNAs. Results A total of 333 potential lncRNAs were screened, and 67 were identified as differentially expressed lncRNAs, including 49 up-regulated and 18 down-regulated lncRNAs. A total of 53 target genes were predicted for differentially expressed lncRNAs. GO enrichment analysis showed that these target genes were mainly enriched in biological process and molecular function, among which Sema7a, Arrb1, and Ccl21b genes may be hub target genes for positive regulation of extracellular regulated protein kinase 1 (ERK1) and ERK2 cascades and may participate in the regulation of collagen expression. KEGG enrichment analysis showed that the target genes of differentially expressed lncRNAs were mainly enriched in cytokine-cytokine receptor interaction, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear factor kappa-B (NF-κB) signaling pathway. Conclusions This study identifies differentially expressed lncRNAs and functional enrichment of their target genes in the liver of mice during the chronic pathogenic stage of S. japonicum infection. Up-regulated lncRNAs may affect biological processes of ERK1/2 cascades and chemokine signaling pathways via target genes Sema7a, Arrb1, and Ccl21b, thereby affecting collagen expression and inflammatory signal pathways, ultimately affecting the development of liver disorders.

OBJECTIVE To provide ideas for clinical diagnosis， treatment and pharmaceutical care of rhino-orbito-cerebral mucormycosis （ROCM）. METHODS The diagnosis and treatment of 1 case of ROCM in which clinical pharmacists participated were analyzed. Combined with treatment guidelines， the actual situation of drug accessibility and economy， clinical pharmacists recommend amphotericin B colloidal dispersion in combination with posaconazole to treat fungal infections. The clinical efficacy， liver and kidney function and electrolytes were monitored. To increase the local concentration of amphotericin B deoxycholate （AmB-D）， clinical pharmacists assisted physicians in determining the dosage and formulation of AmB-D for intrathecal injection， intranasal and eye drops based on the results of blood and cerebrospinal fluid examinations. In response to the situation that the plasma trough concentration of posaconazole had not reached the target， clinical pharmacists recommended that Posaconazole oral suspension was replaced with Posaconazole enteric-coated tablets， and provided the patient with therapeutic drug monitoring （TDM）， individualized medication guidance， and long-term follow-up after discharge. RESULTS The clinician adopted the advice of the clinical pharmacists. After treatment， the patient was discharged from the hospital with medicine after her condition improved. CONCLUSIONS Clinical pharmacists develop individualized treatment protocols for ROCM patients by adjusting dose and dosage forms， providing medication monitoring and TDM to ensure the safety of drug use for patients.

To understand the progress of national schistosomiasis elimination program of China in 2023 and summarize the lessons and experiences, data on the endemic status of schistosomiasis and national schistosomiasis surveillance results in the People’s Republic of China were collected and analyzed at a national level. By the end of 2023, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to consolidate the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan and Hubei provinces were identified to achieve the criteria of transmission interruption in 2020, and Anhui, Jiangxi and Hunan provinces achieved the criteria of transmission interruption in 2023. A total of 451 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2023, including 26 250 endemic villages covering 73 034 500 residents at risk of infections. Among the 451 endemic counties (cities, districts), 78.49% (354/451) achieved the criteria of schistosomiasis elimination and 21.51% (97/451) achieved the criteria of transmission interruption, respectively. In 2023, a total of 4 216 643 individuals received immunological tests, with 47 794 sero-positives identified, and a total of 184 216 individuals received parasitological examinations, with 4 egg-positives detected. A total of 27 768 cases with advanced schistosomiasis were documented in China by the end of 2023. In 2023, 539 548 bovines were raised in schistosomiasis-endemic areas of China, and 125 440 bovines received immunological tests, with 124 sero-positives detected, while no egg-positives were identified among the 133 508 bovines receiving parasitological examinations. In 2023, snail survey was performed at an area of 641 339.53 hm² and 184 819.77 hm² snail habitats were identified, including 51.53 hm² emerging snail habitats and 642.25 hm² reemerging snail habitats. In 2023, there were 20 198 schistosomiasis patients receiving praziquantel chemotherapy, and 598 183 person-time individuals and 283 954 herdtime bovines were given expanded chemotherapy. In 2023, snail control with chemical treatment was performed in 116 347.95 hm² snail habitats, and the actual area of chemical treatment was 65 690.89 hm², while environmental improvements were performed in snail habitats covering an area of 1 334.62 hm². The national schistosomiasis surveillance results showed that the mean prevalence of Schistosoma japonicum infections were both zero among humans and bovines in 2023, and no S. japonicum infection was detected in snails. These data demonstrated that transmission interruption of schistosomiasis had been achieved across all endemic provinces in China in 2023, and the endemic status of schistosomiasis tended to be stable, while advanced cases were predominant among all schistosomiasis cases. However, the areas of snail habitats remained high and cattle re-raising was very common in some regions. Intensified schistosomiasis surveillance and forecast and snail control in high-risk areas are needed.

This report presented the endemic status of schistosomiasis and analyzed the data collected from the national schistosomiasis prevention and control system and national schistosomiasis surveillance program in the People’s Republic of China in 2022. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to maintain the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan, Hubei, Anhui, Jiangxi and Hunan provinces maintained the criteria of transmission control by the end of 2022. A total of 452 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2022, with 27 434 endemic villages covering 73 424 400 people at risk of infections. Among the 452 endemic counties (cities, districts), 75.89% (343/452), 23.45% (106/452) and 0.66% (3/452) achieved the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. In 2022, 4 317 356 individuals received serological tests for schistosomiasis, and 62 228 were sero-positive. A total of 208 646 individuals received stool examinations for schistosomiasis, with one positive and another two cases positive for urine microscopy, and these three 3 cases were imported schistosomiasis patients from Africa. There were 28 565 cases with advanced schistosomiasis documented in China by the end of 2022. Oncomelania hupensis snail survey was performed in 18 891 endemic villages in China in 2022 and O. hupensis snails were found in 6 917 villages (36.62% of all surveyed villages), with 8 villages identified with emerging snail habitats. Snail survey was performed at an area of 655 703.01 hm² and 183 888.60 hm² snail habitats were found, including 110.58 hm² emerging snail habitats and 844.35 hm² re-emerging snail habitats. There were 477 200 bovines raised in the schistosomiasis endemic areas of China in 2022, and 113 946 bovines received serological examinations for schistosomiasis, with 204 sero-positives detected. Among the 131 715 bovines received stool examinations, no positives were identified. In 2022, there were 19 726 schistosomiasis patients receiving praziquantel chemotherapy, and expanded chemotherapy was performed in 714 465 person-time for humans and 234 737 herd-time for bovines in China. In 2022, snail control with chemical treatment was performed at an area of 119 134.07 hm², and the actual area of chemical treatment was 65 825.27 hm², while environmental improvements were performed at an area of 1 163.96 hm². Data from the national schistosomiasis surveillance program of China showed that the mean prevalence of Schistosoma japonicum infections was both zero in humans and bovines in 2022, and no S. japonicum infection was detected in O. hupensis snails. These data demonstrated that the endemic status of schistosomiasis continued to decline in China in 2022, with 3 confirmed schistosomiasis patients that had a foreign nationality and all imported from Africa, and the areas of snail habitats remained high. Further improvements in the construction of the schistosomaisis surveillance and forecast system, and reinforcement of O. hupensis survey and control are required to prevent the re-emerging schistosomiasis.

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M₄) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M₄ positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M₄ PET ligand that allows the non-invasive visualization of M₄ in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [¹⁸F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [¹⁸F] 12 for the M₄-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [¹⁸F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [¹⁸F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [¹⁸F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M₄ PET radioligand with promising attributes. The availability of a clinically validated M₄ PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

Objective To investigate the diagnostic value of cervical vagus nerve cross-sectional area(CAS)for Parkinson's disease(PD).Methods Thirty patients with PD admitted to the People's Hospital of Zhengzhou University from October 2019 to October 2022 were selected as PD group,25 patients with multiple system atrophy(MSA)admitted to the People's Hospital of Zhengzhou University during the same period were selected as the MSA group,and 30 healthy individuals who underwent physical examination in the People's Hospital of Zhengzhou University during the same period were selected as healthy control group.Cervical vagus CAS of subjects in the three groups were measured by high-resolution ultrasound,and the difference of CAS of cervical vagus nerve was compared among the three groups.The degree of impairment of autonomic nervous function of subjects in the three groups was evaluated by PD autonomic symptom scale(SCOPA-AUT).The diagnostic value of cervical vagus nerve CAS for PD was analyzed by receiver operating characteristic(ROC)curve.Results The CAS of the right cervical vagus nerve of subjects was significantly larger than that of the left in the healthy control group and PD group(P＜0.05);there was no significant difference in CAS of bilateral cervical vagus nerve of subjects in the MSA group(P＞0.05).The CAS and average CAS of bilateral cervical vagus nerve of subjects in the PD group and MSA group were significantly lower than those in the healthy control group(P＜0.01).The CAS of the right vagus nerve of subjects in the MSA group was significantly lower than that in the PD group(P＜0.05);there was no significant difference in CAS and the average CAS of the left vagus nerve between the MSA group and the PD group(P＞0.05).The total score of SCOPA-AUT and gastrointestinal(GI),cardiovascular(CV),urinary(UR)and sexual(SX)scores of subjects in the PD group and MSA group were significantly higher than those in the healthy control group(P＜0.01).The total score of SCOPA-AUT and UR,SX scores of subjects in the MSA group were significantly higher than those in the PD group(P＜0.05).There was no significant difference in temperature(TH)and pupil(PU)of subjects among the three groups(P＞0.05).Pearson correlation analysis showed that the CAS of cervical vagus nerve of PD patients was not correlated with the total score of SCOPA-AUT and the UR,TH,PU,SX scores(r=-0.143,0.281,0.297,0.265,0.312;P＞0.05).The CAS of cervical vagus nerve of PD patients was negatively correlated with GI and CV scores(r=-0.683,-0.373;P＜0.05).ROC curve analysis showed that the area under the curve of cervical vagus nerve for diagnosing PD was 0.870(95％confidence interval:0.773-0.966,P＜0.05);the critical value was 3.064 mm2,the sensitivity was 96％,and the specificity was 67％.The area under the curve of CAS of cervical vagus nerve in differential diagnosis of PD,MSA was 0.680(95％confidence interval:0.537-0.823,P＜0.05).The sensitivity and specificity for the diagnosis of MSA were 68％and 70％when the CAS of the cervical vagus nerve＜2.709 mm2.Conclusion The CAS of cervical vagal nerve has high clinical diagnostic value for PD,and it provides a new way to improve the diagnosis rate of PD.

ObjectiveT o explore the influence of patch shape for intraventricular tunnel (IVT) construction on biomechanical performance of the double outlet right ventricle after correction. Methods Based on the idealized IVT model, a two-dimensional IVT patch was designed. Six groups of patch models with the rhombic long-to-short axis ratio of 1∶0.625, 1∶0.3, 1∶0.2, 1∶0.15, 1∶0.125, 1∶0.1 were established according to the difference between the long and short axis of the rhombus patch in the turning part, and finite element analysis method was used to numerically simulate the process of stitching, holding and propping up the patch into a three-dimensional (3D) IVT model. Results The maximum stresses on suture line of 6 patch models were mainly concentrated at acute-angle corners of the rhombus. As rhombic long-to-short axis ratio of the patch increased, the maximum stress of the IVT suture line first decreased and then increased, and the volume showed an increasing trend. The pressure difference between two ends of the tunnel first decreased and then increased. The patch with the long-to-short axis ratio of 1∶0.15 had a uniform surface stress distribution, and the maximum stress on the suture line was the smallest. Meanwhile the right ventricular volume was less encroached on, and the pressure difference at both ends of the tunnel was small. Conclusions The IVT shape can influence stresses of suture line, the right ventricle volume and the pressure difference of IVT with non-monotonic variations. The suture effect of the patch with the long-to-short axis ratio of 1∶0.15 is relatively better among the constructed models.