Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

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

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

Traditional Chinese medicine(TCM)exerts integrative effects on complex diseases owing to the char-acteristics of multiple components with multiple targets.However,the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians,which has been a major challenge in the global acceptance and application of TCM.Therefore,a standardized TCM prescription system needs to be explored to promote its clinical application.In this study,we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation.We tested its efficacy against intracerebral hemorrhage(ICH).First,the top 100 ICH targets in the GeneCards database were screened according to their relevance scores.Then,SymMap and Traditional Chinese Medicine Systems Pharmacology(TCMSP)databases were applied to find out the target-related ingredients and ingredient-containing herbs,respectively.The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets.The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions.The absorbed components in the serum were detected.In a mouse model of ICH,the new prescription exerted multifaceted effects,including improved neurological function,as well as attenuated neuronal damage,cell apoptosis,vascular leakage,and neuroinflammation.These effects matched well with the core pathological changes in ICH.The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise,multipronged,unbiased,and standardized TCM prescriptions for complex diseases.This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01％and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3％and 61％,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective:To evaluate the effect of superior cervical ganglion block (SCGB) on cardiac function and nucleotide like receptor protein 3 (NLRP3) signaling pathway in a rat model of myocardial ischemia-reperfusion (I/R).Methods:Sixty healthy SPF male Sprague-Dawley rats, weighing 250-300 g, aged 2-3 months, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (sham group), myocardial I/R group (IR group), myocardial I/R + normal saline group (IR+ NS group), and myocardial I/R + SCGB group (IR+ SCGB group). Myocardial I/R model was developed by ligation of the left anterior descending branch of the coronary artery for 45 min followed by restoration of blood flow in anesthetized aninals. IR+ SCGB group received SCGB (0.25% ropivacaine 0.1 ml) at 10 min before reperfusion once a day for 2 consecutive weeks, while 0.9% sodium chloride was given instead of ropivacaine in IR+ NS group. Blood samples were collected at 24 h and 14 days of reperfusion for determination of serum concentrations of norepinephrine (NE), troponin T (TnT), tumor necrosis factor-alpha (TNF-α), interleukin-18 (IL-18) and IL-1β by enzyme-linked immunosorbent assay. Echocardiography was performed before ischemia and at 14 days of reperfusion, and left ventricular short axis shortening rate (FS), ejection fraction (EF), and cardiac output (CO) were measured. The rats were sacrificed at 14 days of reperfusion and the hearts were taken for determination of the contents of norepinephrine (NE) in myocardial tissues in the infarction area (by enzyme-linked immunosorbent assay), percentage of myocardial fibrosis area (by Masson staining), M1 macrophage marker CD68 + cell count in the infarction area (by immunohistochemical method), and expression of NLRP3 and gasdermin D (GSDMD) in myocardial tissues (by Western blot). Results:Compared with Sham group, the serum concentrations of TnT, TNF-α, IL-18 and IL-1β, percentage of myocardial fibrosis area, and NE levels in serum and myocardial tissues were significantly increased, the expression of NLRP3 and GSDMD in myocardial tissues was up-regulated, CD68 + cell count was increased, and EF, CO and FS were decreased in IR group ( P<0.05). Compared with IR group, the serum concentrations of TnT, TNF-α, IL-18 and IL-1β, percentage of myocardial fibrosis area, and NE levels in serum and myocardial tissues were significantly decreased, the expression of NLRP3 and GSDMD in myocardial tissues was down-regulated, CD68 + cell count was decreased, and EF, CO and FS were increased in IR+ SCGB group ( P<0.05), and no statistically significant changes were found in the parameters mentioned above in IR+ NS group ( P>0.05). Conclusions:SCGB can improve the cardiac function in a rat model of myocardial I/R, and the mechanism may be related to the inhibition of NLRP3 signaling pathway.

The ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS~E) technology was employed to compare the chemical components between the aerial and underground parts of Coptis chinensis samples from different batches. According to the retention time, molecular ion peak, and LC-MS~E fragment information of the reference substances and available literature, we identified a total of 40 components. Thirty-three and 31 compounds were respectively identified in the underground part(taproots) and the aerial part(stems and leaves) of C. chinensis. Among them, 24 compounds, including alkaloids(e.g., berberine and jatrorrhizine) and phenolic acids(e.g., chlorogenic acid, quinic acid, and tanshinol), were common in the two parts. In addition, differential components were also identified, such as magnoline glucoside in the underground part and(±) lariciresionol-4-β-D-glucopyranoside in the aerial part. The analysis of fragmentation pathways based on spectra of reference substances indicated the differences among samples of different batches. Furthermore, we performed the principal component analysis(PCA) for the peak areas of C. chinensis in different batches. The results showed that the underground part and the aerial part were clearly clustered into two groups, indicating that the chemical components contained in the two parts were different. Furthermore, the results of partial least squares discriminant analysis(PLS-DA) identified 31 differential compounds(VIP value>1) between the underground part and the aerial part, mainly including alkaloids, phenolic acids, lignans, and flavonoids. This study proves that C. chinensis possesses great development potential with multiple available compounds in stems and leaves. Moreover, it sheds light on for the development and utilization of non-medicinal organs of C. chinensis and other Chinese medicinal herbs.
Chromatography, High Pressure Liquid/methods* ; Coptis chinensis ; Spectrometry, Mass, Electrospray Ionization/methods* ; Tandem Mass Spectrometry/methods* ; Technology