OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

In the present study, the antibacterial spectrum of turmeric extract was analyzed by measuring the minimum inhibitory concentration (MIC), and the antibacterial mechanism of turmeric extract was elaborated by determining its effects on the permeability and integrity of the cytoplasmic membrane, energy metabolism, and the morphology of the tested bacteria (Bacillus subtilis) with the highest susceptibility to the extract. The results showed that turmeric extract possessed broad-spectrum antibacterial activity against Gram-positive, Gram-negative bacteria and fungi, especially against Bacillus subtilis, with the MIC of 0.5 mg·mL^-1. Turmeric extract disrupted the liposome membrane and released calcein encapsulated within it. The permeability of the bacterial cell membrane was increased, leading to leakage of intracellular K⁺, Ca²⁺and cell wall proteins, and the integrity of the cell membrane was broken down, causing leakage of intracellular proteins and polysaccharides. Scanning electron microscope observation confirmed that the bacteria treated with turmeric extract was severely deformed. Simultaneously, cellular energy metabolism was affected, resulting in a significant reduction in the intracellular ATP content and ATPase activity in bacteria. In summary, the antibacterial mode of turmeric extract is closely related to its disruption of bacterial membrane structure.

Objective To investigate the protective effect and mechanism of acellular nerve allografts(ANA)combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury(SNI).Methods Totally 50 male adult SD rats were randomly selected for this experiment.Ten rats were prepared for the ANA.Forty male SD rats were randomly divided into normal group,model group,ANA group and combinational group,with 10 rats in each group.The SNI model was established by cutting off the nerves 10 mm at the 5 mm on the inferior border of piriformis after separating the right sciatic nerves.The rats in the ANA group were bridged with ANA to the two broken ends of injured nerves.The rats in the combinational group were treated with electroacupuncture 2 days after ANA bridging,Huantiao(GB30)and Yanglingquan(GB34)were performed as the acupuncture points,each electroacupuncture lasted 15 minutes and 7 days as a course of treatment,4 courses in all.Sciatic nerve conduction velocity was measured by electrophysiology to evaluate the regeneration of damaged axons.Morphology of spinal ganglia was observed by Nissl staining.The expression of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected by Western blotting and immunofluorescent staining.Results Compared with the normal group,the sciatic nerve conduction velocity in model group decreased significantly(P<0.01),Nissl bodies in neurons of spinal ganglia were swollen and dissolved,with incomplete structure and the number decreased dramatically(P<0.01),while the level of NGF and BDNF also decreased significantly(P<0.01).Compared with the model group,the sciatic nerve conduction velocity in ANA and combinational groups strongly increased(P<0.01),the damage of Nissl bodies in neurons of spinal ganglia reduced and the number obviously increased(P<0.01),the level of NGF and BDNF increased considerably(P<0.01).Compared with the ANA group,the sciatic nerve conduction velocity in combinational group increased significantly(P<0.01),the morphology of Nissl bodies in neurons of spinal ganglia were more regular and the number increased(P<0.01),moreover,the level of NGF also increased significantly(P<0.01).Conclusion ANA combined with electroacupuncture can enhance the sciatic nerve conduction velocity,improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of NGF and BDNF proteins,especially the expression of NGF protein.

In this study, a high-performance liquid chromatography method was established to simultaneously determine three flavonoids including hesperidin (HES), nobiletin (NOB) and tangeretin (TAN) in 10 batches of Citrus reticulata 'Chachi' planted and collected in Xinhui District, Jiangmen City, Guangdong Province. Moreover, we studied the metabolism and transformation of three flavonoids in liver and intestinal flora in vitro, and sequenced 16S rRNA of bacteria flora samples after incubation. The RP-HPLC system consisted of Alltima C18 column (250 mm × 4.6 mm, 5 μm) and a mobile phase of water (A) - methanol (B). The column temperature was 25 ℃ and the detection wavelength was both 283 nm and 330 nm while the flow rate was 1.0 mL·min^-1. The results showed that the retention time of HES, NOB and TAN ranged from 12.313 min to 34.271 min. The content of HES, NOB and TAN in 10 batches of Citrus reticulata 'Chachi' was 26.81-39.80 mg·g^-1, 4.06-7.90 mg·g^-1 and 1.81-3.93 mg·g^-1, respectively. There were differences in the content of flavonoids in different batches and growing areas. The three flavonoids were metabolized in various degrees after incubation of rat and human liver S9, cytosol, microsomes or intestinal flora in vitro, especially HES. The results of 16S rRNA showed that the main flavonoids of Citrus reticulata 'Chachi' could regulate lipid metabolism by regulating intestinal flora related to energy metabolism. This study established a rapid, simple, reproducible and stable quantitative analysis method for detecting the main flavonoids in Citrus reticulata 'Chachi' which evaluated the content of flavonoids from Citrus reticulata 'Chachi' in different growing areas and different storage periods. The intestinal bacteria can metabolize and transform the flavonoids of Citrus reticulata 'Chachi' to varying degrees, which provides a valuable scientific basis for the subsequent study on the material basis of the efficacy of Citrus reticulata 'Chachi' from the perspective of metabolism. Animal experiments were approved by the Medical Ethics Committee of Guangdong Jiangmen Chinese Medicine College (No. 20190419).

OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome. METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded. RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05). CONCLUSION Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).
Humans ; Paroxetine/adverse effects* ; Spleen ; Anxiety ; Syndrome ; Medicine, Chinese Traditional ; Treatment Outcome ; Double-Blind Method

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.
Child ; Female ; Male ; Humans ; Retrospective Studies ; Cytokine Release Syndrome ; COVID-19/complications* ; SARS-CoV-2 ; Brain Diseases/etiology* ; Prognosis ; Seizures ; Cytokines

Aim To investigate the regulatory effects of 3-bromopyruvate (3-BrPA) on apoptosis and autophagy of fibroblast-like synoviocytes (FLS) in rats based on AMPK/mTOR signaling pathway and the underlying mechanism. Methods FLS of rats in vitro were cultured and induced by tumor necrosis factor-α (TNF-α) to construct a model of rheumatoid arthritis (R A). MTT assay was used to explore the optimal concentration of TNF-α and 3 -BrPA for induction and treatment of FLS. The effects of 3-BrPA on the migration and invasion of FLS were detected by Wound healing assay and Transwell assay. The apoptosis of FLS was tested by flow cytometry and mitochondrial membrane potential assay kit (JC-1). Moreover, FLS autophagic flux was detected by mCherry-EGFP-LC3B-overexpressed plasmids, and the expression of apoptosis/autophagy-related proteins as well as AMPK/mTOR pathway-related proteins were detected by Western blot. Results 3-BrPA (15 μmol • L) significantly inhibited the proliferation, migration, and invasion of FLS stimulated by TNF-a (25 μg • L

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.
End Stage Liver Disease ; Follow-Up Studies ; Humans ; Liver Cirrhosis/drug therapy* ; Middle Aged ; Peripheral Blood Stem Cells ; Severity of Illness Index ; Treatment Outcome