This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

Objective To investigate the correlation and predictive effect of serum CD4+/CD8+T lympho-cyte ratio combined with magnetic resonance angiography(MRA)on recurrence of cerebral infarction.Meth-ods A total of 153 patients with acute cerebral infarction admitted to the Zhenjiang First People's Hospital from January 2021 to February 2022 were selected.CD4+/CD8+T lymphocyte ratio of patients was deter-mined,vascular stenosis score and collateral circulation filling score were evaluated by MRA.The patients were followed up for 1 year,including 34 patients with recurrent cerebral infarction as recurrent cerebral in-farction group,107 patients without recurrent cerebral infarction as the non-recurrent cerebral infarction group,12 patients were excluded due to other causes of loss of follow-up,and the receiver operating character-istic(ROC)curve for using the indicators to predict the recurrent cerebral infarction was drawn.Results The CD4+/CD8+T lymphocyte ratio in recurrent cerebral infarction group was significantly higher than that in non-recurrent cerebral infarction group(P<0.05).Vascular stenosis score and collateral circulation filling score in recurrent cerebral infarction group were lower than those in non-recurrent cerebral infarction group(P<0.05).The recurrence of cerebral infarction was correlated with CD4+/CD8+T lymphocyte ratio,vascu-lar stenosis score and collateral circulation filling score(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of CD4+/CD8+T lymphocyte ratio,vascular stenosis score,and collateral circulation filling score to predict recurrent cerebral infarction was 0.975,0.889,and 0.935,respectively,and the AUC of recurrent cerebral infarction was 0.994 when combined with the three factors.The AUC of cerebral infarction recurrence was significantly higher than that of each index alone.Conclusion Serum CD4+/CD8+T lympho-cyte ratio combined with MRA vascular stenosis score and collateral circulation filling score have high efficacy in the diagnosis of recurrent cerebral infarction,which have predictive value for recurrent cerebral infarction.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.
Humans ; Randomized Controlled Trials as Topic ; Acupuncture Therapy/methods* ; Pain ; Pain Management ; China

Thirty-one phenolic constituents were isolated and purified from the 95% ethanol extract of Sanguisorbae Radix by using various chromatographic techniques, including macroporous resin, silica gel, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated by physicochemical properties, spectroscopic data (MS and NMR) and electronic circular dichroism (ECD) spectra, and identified as 3-methoxyl-2S,3S-epoxyflavanone (1a), 3-methoxyl-2R,3R-epoxyflavanone (1b), longifoin B (2), longifoin C (3), eriodictyol (4), naringenin (5), liquiritigenin (6), 5,3ʹ-dihydroxy-7,4ʹ-dimethoxyflavanone (7), naringenin-7-O-β-D-glucopyranoside (8), dihydroquercetin (9), dihydrokaempferol (10), (-)-garbanzol (11), (2R,3R)-4-methoxyl-distylin (12), kaempferol (13), quercetin (14), α,4,2′,4′-tetrahydroxydihydrochalcone (15), phloretin (16), (+)-catechin (17), ethyl (+)-cyanidan-3-ol-8-carboxylate (18), phyllocoumarin (19), methyl 3-methoxy-4,5-dihydroxybenzoate (20), 4,5-dimethoxy-3-hydroxybenzoic acid methyl ester (21), 3,4′-di-O-methylellagic acid (22), 3,4,3′-O-trimethylellagic acid (23), 3,3ʹ,4ʹ-O-trimethylellagic acid-4-O-β-D-xyloside (24), (3R)-thunberginol C (25), resveratrol (26), 1-hydroxypinoresinol (27), (7S,8S)-3-methoxy-3′,7-epoxy-8,4′-oxyneoligna-4,9,9′-triol (28), emodin-8-O-β-D-glucoside (29), phloracetophenone (30) and 4-(4′-hydroxyphenyl)-butan-2-one (31). Among them, compound 1a and 1b is a pair of new flavonoid enantiomers, compounds 2 and 3 are a pair of new epimers, while compounds 4, 5, 6, 9, 10, 13, 16 and 26 were obtained from S. officinalis for the first time, compounds 7, 8, 27, 30 and 31 were isolated for the first time from the S. officinalis genus, and compounds 11, 12, 15, 18, 19, 25, 28 and 29 were isolated for the first time from the Rosaceae. The antioxidant activities of compounds 1-24 were evaluated by activating the Nrf2 transcriptional pathway, which were measured by the dual-luciferase reporter gene assay in 293T cells. Compounds 4, 6-10, 12, 14, 17, 19, 20 and 22-24 showed significant Nrf2 agonistic effect compared with the control group at 25 μmol·L^-1, which provided reference for the research of their antioxidant activity.

Social behavior is extremely important for the physical and mental health of individuals, their growth and development, and for social development. Social behavioral disorders have become a typical clinical representation of a variety of psychiatric disorders and have serious adverse effects on the development of individuals. The prefrontal cortex, as one of the key areas responsible for social behavior, involves in many advanced brain functions such as social behavior, emotion, and decision-making. The neural activity of prefrontal cortex has a major impact on the performance of social behavior. Numerous studies demonstrate that neurons and glial cells can regulate certain social behaviors by themselves or the interaction which we called neural microcircuits; and the collaboration with other brain regions also regulates different types of social behaviors. The prefrontal cortex (PFC)-thalamus projections mainly influence social dominance and social preference; the PFC-amygdala projections play a key role in fear behavior, emotional behavior, social exploration, and social identification; and the PFC-nucleus accumbens projections mainly involve social preference, social memory, social cognition, and spatial-social associative learning. Based on the above neural mechanism, many studies have focused on applying the non-invasive neurostimulation to social deficit-related symptoms, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES) and focused ultrasound stimulation (FUS). Our previous study also investigated that repetitive transcranial magnetic stimulation can improve the social behavior of mice and low-intensity focused ultrasound ameliorated the social avoidance behavior of mice by enhancing neuronal activity in the prefrontal cortex. In this review, we summarize the relationship between neurons, glial cells, brain projection and social behavior in the prefrontal cortex, and systematically show the role of the prefrontal cortex in the regulation of social behavior. We hope our summarization will provide a reference for the neural mechanism and effective treatment of social disorders.

Objective To investigate the inhibitory effect of farrerol on inflammation and abnormal muscle tone of cerebral basilar artery in mice induced by high salt and its molecular mechanism based on the Janus kinase 2(JAK2)/Transcription activator 3(STAT3)pathway.Methods A total of fifty C57BL/6J mice were randomly divided into normal group(normal feeding),model group(high salt diet),experimental-L group(high salt diet+oral administration of 12.5 mg·kg-1·d-1 farrerol),experimental-M group(high salt diet+oral administration of 25 mg·kg-1·d-1 farrerol)and experimental-H group(high salt diet+oral administration of 50 mg·kg-1·d-1 farrerol).The model was prepared for 12 weeks.The contractile response of the cerebral basilar artery of mice in each group to vasoconstrictor was recorded with myographs.Enzyme linked immunosorbent assay(ELISA)were used to detect the levels of inflammatory factor.The protein expression levels of JAK2/STAT3 pathway related proteins were detected by Western blot.Results In the normal group,model group,experimental-L group,experimental-M group,experimental-H group,the contraction effects of the cerebral basilar artery to 60 mmol·L-1 potassium chloride(KCl)were(2.19±0.13),(2.66±0.11),(2.52±0.09),(2.41±0.08)and(2.25±0.10)mN;the contraction effects to 10-5 mol·L-1 vasopressiu(AVP)were(1.98±0.09),(2.46±0.08),(2.33±0.12),(2.11±0.10)and(2.05±0.06)mN;the contraction effects to 2.5 mmol·L-1 calcium chloride(CaCl2)were(1.77±0.08),(2.09±0.09),(2.03±0.08),(1.94±0.05)and(1.86±0.06)mN;in the serum,the levels of interleukin(IL)-1β were(10.10±3.21),(47.28±4.78),(40.16±3.98),(35.87±4.12)and(20.32±3.17)pg·mL-1;the levels of tumor necrosis factor-α(TNF-α)were(60.26±5.43),(134.32±4.15),(110.65±3.56),(90.79±5.25)and(81.54±6.23)pg·mL-1;the levels of chemokine ligand 3(CCL3)were(68.93±4.16),(146.37±5.73),(128.29±4.38),(100.25±6.82)and(84.16±3.89)pg·mL-1;the protein expression levels of JAK2 were 0.52±0.05,1.28±0.07,1.11±0.06,0.88±0.09 and 0.75±0.04;the protein expression levels of STAT3 were 0.58±0.07,1.93±0.10,1.62±0.04,1.34±0.06 and 0.88±0.09,respectively.The above indicators in the model group were significantly higher than the normal group(all P＜0.01);compared to the model group,the above indicators in the experimental-M and-H groups were significantly reduced(P＜0.05,P＜0.01).Conclusion Farrerol maybe improve the inflammation and abnormal muscle tone of cerebral basilar artery in mice induced by high salt by downregulating JAK2/STAT3 pathway.

Objective:To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD).Methods:The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children′s Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed.Results:The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant.Conclusions:β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

Objective To analyze the effect of Liujunzi Decoction on serum phosphorylated P38 mitogen-activated protein kinase(p-P38MAPK)in patients with chronic obstructive pulmonary disease(COPD).Methods A total of 112 patients with COPD of lung-spleen qi deficiency type who were treated in Hangzhou Lin'an District Hospital of Traditional Chinese Medicine from September 2020 to September 2022 were selected as the research objects.According to the treatment method,the patients were divided into an observation group and a control group,with 56 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Liujunzi Decoction on the basis of treatment for the control group.Seven days constituted a course of treatment,and the two groups were treated for 3 months.The changes of lung function indicators,6-minute walking distance(6MWD),clinical chronic obstructive pulmonary disease questionnaire(CCQ)score,and serum levels of inflammatory factors and p-P38MAPK in the two groups were observed before and after treatment.Moreover,the clinical efficacy,incidence of adverse reactions and number of acute episodes within one year were compared between the two groups.Results(1)After 3 months of treatment,the total effective rate of the observation group was 94.64%(53/56),and that of the control group was 73.21%(41/56).The intergroup comparison(tested by chi-square test)showed that the curative effect of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the forced vital capacity(FVC),forced expiratory volume in one second(FEV1),FEV1/FVC and 6MWD in the two groups were increased(P＜0.05),and the CCQ scores were decreased(P＜0.05)when compared with those before treatment,and the increase of FVC,FEV1,FEV1/FVC and 6 MWD and the decrease of CCQ scores in the observation group were significantly superior to those in the control group(P＜0.01).(3)After treatment,the levels of serum interleukin 4(IL-4),interleukin 6(IL-6),interleukin 8(IL-8)and p-P38MAPK in the two groups were lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)The incidence of adverse reactions in the observation group was 3.57%(2/56)and that in the control group was 7.14%(4/56),and there was no significant difference between the two groups(P＞0.05).(5)The number of acute episodes within one year in the observation group was(0.68±0.12)times,which was significantly less than that in the control group[(1.46±0.37)times],and the difference was statistically significant(P＜0.01).Conclusion Liujunzi Decoction exerts certain effect in the treatment of COPD patients with lung-spleen qi deficiency syndrome.It can effectively inhibit the activation of p-P38MAPK signaling pathway,relieve the symptoms such as expectoration and dyspnea,improve lung function,alleviate inflammatory response,reduce the number of acute episodes,and has high safety.

Objective To investigate the protective effect of placental mesenchymal stem cells(P-MSCs)on pancreatic trauma(PT)in rats.Methods Sixty healthy adult male SD rats were randomly divided into control group,pancreatic trauma group(inject 1 ml of PBS solution locally in the pancreatic injury area and around the trauma area),and P-MSCs group[inject 1 ml of P-MSCs(1×106/ml)locally in the pancreatic injury area and around the trauma area],with 20 rats in each group.The pancreatic trauma rat model was established using a traumatic pressure of 400 kPa.Five rats were sacrificed at 1,3,5,and 7 d after modeling in each group,and serum and pancreatic tissue were collected.HE staining was used to observe the pathological changes of pancreatic tissue and pathological scores were performed.The ELISA method was used to measure the concentrations of serum amylase(AMS),lipase(LPS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10,and transforming growth factor-β1(TGF-β1),as well as the activities of myeloperoxidase(MPO)and superoxide dismutase(SOD)in pancreatic tissue.The TUNEL method was used to observe the level of apoptosis in pancreatic tissue was observed by the TUNEL method.Results Compared with control group,pancreatic trauma group and P-MSCs group showed significant differences after pancreatic trauma,including the generation of peritoneal fluid increased(P<0.05),the ratio of pancreas to body weight and the total score of pancreatic tissue pathological damage increased(P<0.05),and serum levels of AMS,LPS,TNF-α,IL-6,and MPO activity increased early and showed a decreasing trend over time(P<0.05),while anti-inflammatory factors IL-10 and SOD activity showed an increasing trend over time(P<0.01),level of TGF-β1 in the early decline showed an upward trend over time(P<0.01),and the apoptosis index(AI)significantly increased(P<0.001).Compared with pancreatic trauma group,P-MSCs group showed an improvement in the overall morphology of pancreatic tissue,the generation of peritoneal fluid decreased(P<0.001),the pancreas to body weight ratio and the total score of pancreatic tissue pathological damage decreased(P<0.05),and serum levels of AMS,LPS,IL-6,TNF-α and MPO activity returned to normal levels faster(P<0.05);and the rate of anti-inflammatory factors IL-10,TGF-β1 and SOD activity elevation increased(P<0.05),the AI increased(P<0.001).Conclusion P-MSCs can achieve therapeutic effects on pancreatic trauma in rats by promoting pancreatic tissue repair,reducing local and systemic inflammation,improving tissue oxidative stress,and enhancing pancreatic acinar cell apoptosis.

AIM:The effects and mechanisms of paeoniflorin(PF)on sepsis-associated acute kidney injury(SA-AKI)in mice were investigated based on cellular pyroptosis and the JNK/NEK7/NLRP3 pathway.METHODS:A murine SA-AKI model was established by intraperitoneal injection of lipopolysaccharide(LPS).Twenty-four male C57BL/6J mice aged 6～8 weeks were divided into four groups(n=6)using a randomized numerical table method:control(Con)group(an equal amount of DMSO-containing PBS was injected intraperitoneally at the same time);LPS group(LPS was injected intraperitoneally at 15 mg/kg);LPS+PF group(PF was injected intraperitoneally at 50 mg/kg for 30 min prior to modeling);and LPS+PF+anisomycin group(intraperitoneal injection of PF 50 mg/kg and JNK agonist anisomycin 20 mg/kg 30 min before modeling).Samples were taken 24 h after modeling.HE staining was used to observe the pathological changes in renal tissues,and Paller scoring of renal injury was performed.ELISA was used to detect the levels of renal in-jury markers:blood creatinine(Scr),kidney injury molecule 1(KIM-1),and the inflammatory factors interleukin 1β(IL-1β)and IL-18.Western blot was used to detect changes in phosphorylated c-Jun N-terminal kinase(p-JNK),NIMA-relat-ed expressed kinase 7(NEK7),nucleotide oligomerization domain(NOD)-like receptor protein 3(NLRP3),and N-ter-minal fragment of gasdermin D(GSDMD-N)protein levels.RESULTS:Compared with the Con group,HE staining in the LPS group showed congestion and edema in renal tissues,granular or cell-like tubular patterns in the dilated tubular lu-men of renal tubules,and congestion and edema in the renal interstitium.Paller scores,Scr,serum KIM-1,IL-1β,and IL-18 levels in renal tissues were elevated(P<0.05).The expression of p-JNK,NEK7,NLRP3,and GSDMD-N also in-creased(P<0.05).Compared with the LPS group,the LPS+PF group exhibited reduced renal histopathological injury,decreased Paller score,Scr,serum KIM-1,IL-1β,and IL-18 levels(P<0.05),and decreased protein expression of p-JNK,NEK7,NLRP3,and GSDMD-N(P<0.05).Compared with the LPS+PF group,the LPS+PF+anisomycin group showed increased renal histopathological injury,Paller score,Scr,serum KIM-1,IL-1β,and IL-18 levels(P<0.05),and increased expression of p-JNK,NEK7,NLRP3,and GSDMD-N(P<0.05).CONCLUSION:Paeoniflorin may at-tenuate SA-AKI by inhibiting the JNK/NEK7/NLRP3 signaling pathway and downregulating cellular pyroptosis.