ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

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 study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Aim To study the neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/ reperfusion rats and its mechanism. Methods Sixty SD rats were randomly divided into model group, low, middle and high dose groups of Herba siegesbeckiae, and Sham operation group, and the drug was given continuously for seven days. The degree of neurologic impairment was evaluated by mNSS, and the infarct volume was measured by MRI. The number of Nissl-posi- tive cells was detected by Nissl staining, and the apop- tosis was accessed by Tunel staining. Furthermore, the expression of Bax, Bcl-2 and NeuN was observed by Western blot, and the expression of NeuN was detected by immunofluorescence staining. The expression of IL- 1β, TNF-α and IL-6 mRNA was performed by RT- qPCR. Results The mNSS score and the volume of ischemic cerebral infarction in the model group were significantly increased, and Herba siegesbeckiae extract treatment significantly decreased the mNSS score and infarct volume (P<0.05, P<0.01). Herba siegesbeckiae extract could increase the number of Nissl-pos- itive cells and the expression of NeuN (P<0.01), and reduce the number of Tunel-positive cells (P<0.01). Western blot showed that Herba siegesbeckiae extract inhibited the expression of Bax, increased Bcl-2 and NeuN in ischemic brain tissue (P<0.01). RT-qPCR showed that Herba siegesbeckiae extract inhibited the expression of IL-1 β, TNF-α and IL-6 mRNA in the is-chemic brain tissue (P<0.01). Conclusions Herba siegesbeckiae extract can reduce the cerebral infarction volume, improve the neurological function damage, inhibit the apoptosis of nerve cells and the expression of inflammatory factors and promote the expression of NeuN, there by exerting protective effects on MCAO rats.

Gastrointestinal dyskinesia is a central factor contributing to the development of functional dyspepsia(FD),which is characterized by the rupture of the gastrointestinal nerve-Cajal interstitial cell-smooth muscle network.Gan Yu Pi Xu are similar to endoplasmic reticulum stress(ERs)-mitochondrial autophagy homeostasis imbalance.Mitochondrial autophagy disorders are the biological basis of Pi Xu,and Gan Yu is the macroscopic manifestation of ERs,and regulation of ERs-mitochondrial autophagy pathway is an important way to prevent and control FD.In this paper,we start from the theory of"liver-spleen correlation",combine the changes of endoplasmic reticulum and mitochondria in the process of gastrointestinal dyskinesia,reveal the correlation between the pathogenesis of Gan Yu Pi Xu and the autophagy of ERs and mitochondria,and elucidate the mechanism of gastrointestinal dyskinesia by the method of Shu Gan Jian Pi,so as to provide a new point of view for the treatment of gastrointestinal dyskinesia in FD.

Objective To explore the effect of modified Shaoyao Gancao Decoction combined with acupuncture on Oswestry Disability Index(ODI)of patients after surgery for osteoporotic vertebral compression fracture(OVCF).Methods A total of 94 patients with OVCF of liver-kidney deficiency and yin-blood deficiency type were randomly divided into an observation group and a control group,with 47 cases in each group.Both groups were treated with surgical treatment by percutaneous balloon kyphoplasty or percutaneous vertebroplasty.After the operation,the control group was given acupuncture therapy,and the observation group was treated with modified Shaoyao Gancao Decoction combined with acupuncture therapy.Both groups were treated for 12 weeks(3 months in total).The changes of pain visual analogue scale(VAS)score,ODI score,bone mineral density(BMD)of lumbar vertebrae 2-4(L2-4),femoral neck,Wards triangle and total hip,and serum levels of bone metabolism indicators of type I collagen C-terminal peptide(CTX-1),bone alkaline phosphatase(BALP)and blood calcium in the two groups at different observation time points after operation were observed.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 3 months of treatment,the total effective rate of the observation group was 100.00%(47/47),and that of the control group was 87.23%(41/47).The intergroup comparison(tested by Fisher's exact test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)On the seventh day,first month and third month after operation,the pain VAS score and thoracolumbar function of ODI scores of the two groups were significantly lower than those at the previous observation time point(P＜0.05),and the decrease of VAS score and thoracolumbar ODI score in the observation group was significantly superior to that in the control group on the seventh day,first month and third month after operation(P＜0.05 or P＜0.01).(3)After treatment(one month after operation),the BMD values of L2-4,femoral neck,Wards triangle and total hip in the two groups were significantly higher than those before treatment(P＜0.05),and the increase of BMD values in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment(one month after operation),the serum levels of bone metabolism indicators of CTX-1,BALP and calcium of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum CTX-1,BALP and calcium levels in the observation group was significantly superior to that in the control group(P＜0.01).Conclusion Modified Shaoyao Gancao Decoction combined with acupuncture exerts certain effect for the treatment of OVCF patients with liver-kidney deficiency and yin-blood deficiency type.The combined therapy can significantly relieve postoperative pain symptoms,improve BMD and bone metabolism,promote the recovery of thoracolumbar function,and effectively enhance the overall efficacy.

Objective To develop a multicolor photoelectroencephalography evoked flash to identify photosensitive epilepsy patients during the selection of naval aircraft pilots.Methods The multicolor photoelectroencephalography evoked flash was composed of a main body,a control box and a bracket.There were four rows of LED lights in the main body,which emitted four colors of light including red,yellow,green and orange,respectively;there were three sockets for signal,light and power and one color changeover switch on the body of the control box,and a control circuit board was fixed at the bottom inside the control box;the bracket had a double-jointed arm folding structure.The flash developed was compared with the coventional photoelectroencephalography evoked flash to verify its effect for inducing photosensitive epilepsy.Results There were no significant differences between the two flashes in the numbers of identified cases with photosensitive epilepsy when the subjects were under awake and closed-eye conditions(P＞0.05).Condusion The flash developed can make up for the deficiency of the coventional photoelectroencephalography evoked flash when selecting naval aircraft pilots.[Chinese Medical Equipment Journal,2024,45(7):112-114]

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Aim To study the effect of salidroside combined with rosavin on ischemic stroke in rats.Methods The model of MCAO was established by u-sing thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside combined with rosavin group,positive control group,and the drug was given continuously for seven days.The infarct volume was measured by MRI and neurological deficit score was evaluated by Zea-Longa.The levels of Ne-uN,BDNF,TGF-β1,p-Smad were observed by West-ern blot and immunofluorescence staining.The expres-sions of IL-1β,TNF-α and IL-6 were performed by RT-qPCR/ELISA.The primary cortical neurons were isolated,OGD/R inducted,divided into the normal group,OGD/R group,salidroside combined with rosa-vin group,and TGF-β1 inhibitor+salidroside com-bined with rosavin group,the drug was given for 24 hours,and the expressions of NeuN,BDNF,IL-1β,TNF-α and IL-6 were measured.Results Salidroside combined with rosavin could decrease the infarct vol-ume,improve the neurological function,promote the levels of Neun,BDNF,TGF-β1,p-Smad,and inhibit the expressions of IL-1β,TNF-α and IL-6.Salidroside combined with rosavin could promote NeuN,BDNF,inhibit IL-1β,TNF-α,IL-6 in primary nerve cells in-duced by OGD/R,and these effects were blocked by TGF-β1 inhibitor.Conclusions Salidroside combined with rosavin has neuroprotective effects on MCAO rats,and primary neurons are induced by OGD/R,and these effects are closely related to the TGF-β pathway.