ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

This article summarizes Professor Li Ziyong's clinical experience with the round-sharp needle.As one of the core needle types in the Huang Di Nei Jing(The Yellow Emperor's Inner Classic)nine-needle system,the round-sharp needle has long been marginalized in clinical practice due to historical discontinuities in its transmission and insufficient research on its morphological characteristics,resulting in its unique therapeutic value remaining largely unrecognized.Through nearly three decades of clinical practice,Professor Li innovatively proposed the acupuncture concept of"unblocking passages and guarding the pivotal mechanism",guided by the Yellow Emperor's Inner Classic principle that"ordinary practitioners focus on the joints,while superior practitioners focus on the pivotal mechanisms".Under this theoretical framework,he has extensively applied the round-sharp needle in clinical settings.With its unique design combining rounded and sharp features,the round-sharp needle demonstrates remarkable clinical efficacy by intervening at the fascial layer and releasing local fascial adhesions.It exhibits rapid onset and stable therapeutic outcomes.This article systematically reviews Professor Li's understanding of the round-sharp needle,its key operational techniques,and clinical case studies,aiming to establish a replicable paradigm for its modern application and promote the clinical translation of classical acupuncture theory.

The view of"inferior practitioner guarding the gate while the superior practitioner keeping the trigger"during the clinical practive was recorded in in Huang Di Nei Jing(Huangdi's Cannon of Medicine).This paper probes into the diagnosis and treatment of bi-syndrome from the perspecitve of"guarding the gate"and"keeping the trigger".It is proposed that the lesion of five body constituents(i.e.,skin,vessel,muscle,tendon,and bone)constitutes the injured"gate"of bi-syndrome,and the disharmony of qi and blood constitutes the"trigger"of the onset of bi-syndrome.The location of lesions will be found through examining the gate,and the state of qi and blood will be confirmed after checking the trigger.For the treatment of bi-syndrome,"guarding the gate"is to enable the normality of five body constituents,and"keeping the trigger"is to maintain the abundance and harmony movement of qi and blood,which cover the consideration of focal lesions and the regulation of holistic qi and blood."Guarding the gate"is as important as"keeping the trigger",and the two are interrelated.Only by carefully examining the gate of the lesions and strictly checking the trigger of qi-blood movement,it is possible to identify the deficiency of healthy qi and the excess of the pathogens,the nature of the pathogens and the severity of illness of bi-syndrome,and then the corresponding therapeutic methods can be performed to achieve the efficacy.The view of"guarding the gate"and"keeping the trigger"expands the clinical approach to the diagnosis and treatment of bi-syndrome.

Objective To compare the clinical effect between laparoscopic temporary long tunneled external ventricular drainage and traditional laparoscopic ventriculoperitoneal shunt in patients with hydrocephalus after traumatic brain injury(TBI).Methods A total of 52 patients who underwent laparoscopic temporary long tunneled external ventricular drainage(external drainage group)or traditional laparoscopic ventriculoperitoneal shunt(traditional shunt group)for hydrocephalus after TBI from October 2018 to October 2021 were retrospectively analyzed.The catheterization time,remission time of intracranial hypertension,average hospital stay,therapeutic effective rate and the incidence of complications were compared between the two groups.Results The total effective rate of the external drainage group was significantly higher than that of the traditional shunt group(92.31%vs 80.77%,P＜0.05).The external drainage group had longer catheterization time and shorter remission time of intracranial hypertension and average hospital stay than the traditional shunt group.The incidence of adverse reactions such as intracranial infection,shunt obstruction and poor healing in the traditional shunt group was significantly higher than that in the external drainage group(19.23%vs 7.69%,P＜0.05).Conclusion Laparoscopic temporary long tunneled external ventricular drainage can achieve better therapeutic effect for hydrocephalus after TBI,and it is recommended in clinical treatment.

Objective : To investigate the effect and mechanism of M2 macrophage polarization induced by HCT116 with highly metastatic colorectal cancer cells on immune escape in colorectal cancer. Methods : After the co-culture of colorectal cancer cells conditioned medium(CM) and PMA-induced M0 macrophages, the polarization of M2 macrophages was observed by flow cytometry, real-time polymerase chain reaction(qPCR) and enzyme-linked immunosorbent assay(ELISA) experiments. The CMM0, CMSW480-Mφ and CMHCT116-Mφ were co-cultured with HCT116 cells, and the expression of programmed death-ligand 1(PD-L1) was detected by Western blot and qPCR. At the same time, the stimulated HCT116 cells were co-cultured with human T lymphocytes to detect the survival of HCT116 cells and the levels of tumor necrosis factor-α(TNF-α) and interferon-γ(IFN-γ). The difference of kruüppel-like factor 4(KLF4) expression between SW480 and HCT116 cells was detected by Western blots, qPCR and ELISA. After pretreatment of HCT116 cells with KFL4 inhibitor Kenpaullone(Ken), the CMHCT116 and CMHCT116+Ken were co-cultured with M0 macrophages and the polarization of M2 macrophages was observed by flow cytometry, qPCR and ELISA. The CMHCT116-Mφ and CM_((HCT116+Ken)-Mφ) was co-cultured with HCT116 cells, and the PD-L1 expression of HCT116 cells was detected by Western blot and qPCR. Results: After the stimulation of M0 macrophages with CM, the proportion of CD11b+CD206+ cells in HCT116-Mφ cells was higher, and the expression of M2 macrophage markers interleukin(IL-10) and transforming growth factor-β(TGF-β) were higher. Compared with the CMSW480-Mφ group, the PD-L1 protein expression level was higher in the CMHCT116-Mφ group. After co-culture with T lymphocytes, the cell survival rate are the most in CMHCT116-Mφ group, while the levels of TNF-α and IFN-γ were the lowest. After the addition of Ken, the polarization ratio and markers of M2 macrophages decreased. Compared with CMHCT116-Mφ group, the expression of PD-L1 in HCT116 cells of the CM_((HCT116+Ken)-Mφ) group decreased. Conclusion Highly metastatic colorectal cancer cells induce polarization of M2 macrophages by secreting KLF4, promote PD-L1 expression in colorectal cancer cells, facilitate tumor immune escape, and provide potential targets for clinical immunotherapy.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.