ObjectiveTo investigate the mechanism of topical treatment of allergic contact dermatitis （ACD） mice with Portulacae Herba based on the nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/nuclear factor-κB （NF-κB） signaling pathway. MethodsA total of 70 6-week-old specific pathogen free （SPF） female Kunming mice were adaptively fed for 1 week and randomly divided into blank group， model group， compound dexamethasone acetate cream group （2.075×10^-2 g·g^-1）， blank matrix cream group， low-dose Portulacae Herba cream group （0.1 g·g^-1）， high-dose Portulacae Herba cream group （0.2 g·g^-1）， and Portulacae Herba + inhibitor group （0.2 g·g^-1 + 30 mg·kg^-1 ML385）， with 10 mice in each group. One day before the experiment， the mice were shaved on the neck and back. Except for the blank group， the mice in the other groups were treated with 2，4-dinitrochlorobenzene （DNCB） to establish an ACD model. After respective administration， the skin lesion of the mice was scored， and the histopathological changes of the skin were stained with hematoxylin-eosin （HE）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， reactive oxygen species （ROS）， superoxide dismutase （SOD） activity， and malondialdehyde （MDA） in serum of mice. The expression of Nrf2/HO-1/NF-κB signaling pathway-related proteins in mouse skin tissue was detected by immunohistochemistry （IHC）， Western blot， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the mice in the model group had an increased skin lesion score （P<0.01）， severe pathological damage to skin tissue， increased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and decreased content of SOD （P<0.01）. In addition， the mRNA and protein expression levels of Nrf2， HO-1， and nuclear factor-κB inhibitor α （IκBα） in skin tissue were up-regulated （P<0.01）， while the protein expression levels of phosphorylated （p）-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.01）. Compared with the model group and the blank matrix cream group， the mice treated with Portulacae Herba had a decreased skin lesion score （P<0.01）， reduced pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and increased content of SOD （P<0.01）. Additionally， the mRNA and protein expression levels of Nrf2， HO-1， and IκBα in skin tissue were down-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were up-regulated （P<0.05，P<0.01）. Compared with the Portulacae Herba + inhibitor group， the high-dose Portulacae Herba cream group had a decreased skin lesion score （P<0.01）， alleviated pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in the serum of mice （P<0.05，P<0.01）， and increased content of SOD （P<0.01）. The protein expression levels of Nrf2， HO-1， and IκBα and the mRNA expression of Nrf2 and HO-1 in skin tissue were up-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.05）. ConclusionPortulacae Herba can improve DNCB-induced ACD skin damage in mice by regulating the Nrf2/HO-1/NF-κB signaling pathway.

Objective To evaluate the stability of tick-borne encephalitis inactivated vaccine(0. 5 mL/dose) with pre-pottingsyringe in order to ensure the effectiveness and safety of the product. Methods The optimized stock solution of tick-borneencephalitis inactivated vaccine(0. 5 mL/dose, pre-potting syringe) was stored at(5 ± 3) ℃ for 120 days. The indicators ofsterility, antigen content, protein content, bovine serum albumin residue and hamster kidney cell protein residue weredetected and compared with those of vaccine before optimization(0. 1 mL/dose, vial). The long-term stability(0-33 monthsat 2-8 ℃), accelerated stability [0, 3, 6 months at(25 ± 2) ℃] and accelerated destruction stability [0, 7, 14 days at(37 ±1) ℃] of the optimized tick-borne encephalitis inactivated vaccine were investigated according to the relevant requirements ofTechnical Guidelines for Stability Research of Biological Products, including appearance, titer, aluminum content, osmoticmolar concentration and other indicators. Results Before and after optimization, all indicators of the stock solution of tick-borne encephalitis inactivated vaccine were qualified. There was no statistically significant difference in bovine serumalbumin residue and hamster kidney cell protein residue(F = 3. 33 and 0. 61, P = 0. 077 and 0. 627, respectively), but theF P differenceofproteincontentwasstatisticallysignificant(=38.07,<0.05),whileallofthemwerewithinthestandard rangeof ≤ 80 μg/mL. After optimization, the indicators of long-term stability, accelerated stability and accelerated destructionstability of the finished product of tick-borne encephalitis inactivated vaccine were all qualified. In the tests of long-termstability, respectively the vaccine titer after optimization was significantly higher than that before optimization(F = 62. 32,P < 0. 05); the differences of osmotic pressure molar concentration were statistically significant(F = 40. 47 and 12. 50 respec-tively, each P < 0. 05), but the fluctuation was controlled within the standard range of 240-320 mOsmol/kg. Conclusion Tick-borne encephalitis inactivated vaccine(0. 5 mL/dose) with pre-potting syringe has good stability under the conditions of long-term storage, transportation and short-term overtemperature, and its quality meets the standard.

OBJECTIVE To study the effects and mechanism of Portulaca oleracea cream on skin pruritus and barrier function in allergic contact dermatitis （ACD） mice. METHODS Low-concentration and high-concentration P. oleracea creams were prepared， with the P. oleracea extract solution （1 g/mL， calculated by crude drug） concentrations of 10% and 20%. Sixty BALB/c mice were randomly allocated into blank group， model group， Mometasone furoate cream group （positive control）， blank matrix cream group， P. oleracea low-concentration and high-concentration cream groups. Except for blank group， ACD model was induced in each group using 2，4-dinitrochlorobenzene solution. The blank group and model groups received normal saline， while the remaining groups were treated with their respective creams， once a day， at a dose of approximately 0.5 g per application， continuously for 14 days. At 24 h post-final administration， skin lesions of mice were observed and scored； pathological changes of skin tissue were observed； serum levels of immunoglobulin E（IgE） and tumor necrosis factor-α （TNF-α） were quantified. mRNA expression of MAS-related G protein-coupled receptors （including MrgprA3， MrgprC11， and MrgprD） in dorsal root ganglion （DRG） was assessed； while protein expressions of skin barrier function-related proteins Claudin-1 and Occludin in skin tissues were determined. RESULTS Compared with blank group， mice in the model group exhibited severe skin damage， characterized by loss of epidermal architecture， hyperkeratosis of the skin tissue， and the infiltration of a large number of inflammatory cells. The skin injury scores， as well as the serum levels of IgE and TNF-α， and the mRNA expression levels of MrgprA3， MrgprC11， and MrgprD in DRG， were all significantly elevated compared to the blank group （P＜0.05 or P＜0.01）； in contrast， the protein expression levels of Claudin-1 and Occludin in the skin tissue were markedly reduced （P＜0.05）. Compared with model group， mice in P. oleracea low-concentration and high- concentration cream groups demonstrated significant alleviation of skin damage， as evidenced by reduced epidermal hyperplasia， mitigated spongiosis in the dermis， and decreased infiltration of inflammatory cells； these quantitative indicators were almost significantly reversed （P＜0.05 or P＜0.01）. No significant differences were observed in the aforementioned skin injuries， pathological alterations， or quantitative indicators between the blank matrix cream group and the model group. CONCLUSIONS P. oleracea may ameliorate skin lesions and restore skin barrier function of ACD mice， the mechanism of which may be associated with downregulating mRNA expressions of MrgprA3， MrgprC11 and MrgprD in DRG， and up-regulating the protein expressions of Claudin-1 and Occludin in skin tissue.

OBJECTIVE: To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). METHODS: Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (P_ETCO₂). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy. RESULTS: With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, P_ETCO₂, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, P_ETCO₂ (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [P_ETCO₂, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage. CONCLUSIONS Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals ; Cardiopulmonary Resuscitation/methods* ; Swine ; Male ; Heart Arrest/therapy* ; Heart Massage/methods* ; Hemodynamics

OBJECTIVE To optimize β-cyclodextrin(β-CD)inclusion process of Cinnamomi Ramulus Formula Granules vola-tile constituents by orthogonal test,based on standard relation and information entropy method.METHODS On the basis of single factor experiments,the ratio of β-CD to aromatic aqueous solution,the inclusion temperature,and the inclusion time were selected as the investigating factors;the inclusion rate,drug loading,and standard relation of cinnamic aldehyde in inclusion complex were used as the evaluation index.The information entropy method was used to determine the weight coefficient of each index,then the comprehen-sive score was calculated,the inclusion process conditions were optimized by orthogonal experiment.The inclusion complex was charac-terized by thin layer chromatography,ultraviolet absorption spectroscopy,Fourier infrared spectroscopy,and X-ray diffraction.RE-SULTS The best inclusion process was that the ratio of β-CD to aromatic aqueous solution was 3∶100(g·mL-1),the inclusion temperature was 50℃,and the inclusion time was 1 h.The average inclusion rate of the obtained inclusion compound was 80.84%,the drug loading was 8.63%,and the standard relation was 0.91.The results of thin-layer chromatography,ultraviolet,infrared spec-troscopy and other characterization experiments showed that the volatile components in the aromatic aqueous solution successfully en-tered the β-CD cavity,and the inclusion complex was successfully prepared.CONCLUSION The optimum inclusion process is sta-ble and feasible,which can provide references for the preparation process of Cinnamomi Ramulus Formula Granules.

Objective To investigate the regulatory mechanism of apurnic/apyrimidinic endonuclease 1(APE1)in the transformation of chronic intestinal inflammation to colitis-associated colorectal cancer(CAC).Methods C64S mutant(APE1C64S)mice and APE1 wild type(APE1WT)mice were randomly divided into experimental group and control group.In vivo CAC model was established by azoxymethane(AOM)and dextran sulfate sodium salt(DSS)solution.Immunohistochemistry(IHC)and multiple IHC(mIHC)assays were used to observe the expression of APE1 and immune cell infiltration in colon tissues of each group.A mouse colon cancer cell line MC38 with stable knockdown of APE1 was constructed by lentivirus transfection,and subcutaneous tumor bearing experiments were performed in APE1WT and APE1C64S mice to confirm that tumor cell-derived APE1 caused immunosuppressive tumor microenvironment.The expression of APE1 and CXCL1[chemokine(C-X-C motif)ligand 1]and the infiltration of immune cells in tumor-bearing specimens were analyzed by IHC and mIHC assays.The tumor specimens of a 28-year-old female patient with CAC from Army Medical Center of PLA were analyzed for the expression of APE1 and CXCL1 and the infiltration of immune cells in the tumor and adjacent inflammatory tissues by IHC and mIHC assays.Results Compared with the control group and APE1WT erperimental group,APE1C64S erperimental group had significantly reduced disease activity index and tumor formation,polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)infiltration,and CD4+and CD8+T cells(P＜0.05).No significant differences were observed in tumor growth and immune cells between APE1WT and APE 1C64S mice bearing subcutaneous tumors.However,in the tumor-bearing experiment using tumor cells with knockdown of APE1,the tumor growth was significantly lower and the number of infiltrated PMN-MDSCs was reduced,while those of CD4+and CD8+T cells were significantly increased(P＜0.05).Furthermore,high expression of APE1 and increased infiltration of PMN-MDSCs were found in the tumor tissues of the young CAC patient,and CD8+T cells were significantly reduced in the tumor tissues compared with the inflammatory tissues(P＜0.05).Conclusion APE1-redox in tumor cells can promote the infiltration of PMN-MDSCs and reduce the number of T cells,thereby forming an immunosuppressive tumor microenvironment and mediating the occurrence and development of CAC.

Objective To understand and assess the quality status of national drug sampling inspection in 2022 and the possible risks of drug quality.Methods With the aim of identifying issues and preventing risks,a sampling model of"dispersed sampling,centralized inspection,exploratory research,and comprehensive evaluation"was used to review the historical inspection data of national drug sampling.The overall quality and potential risks of national drug sampling in 2022 were analyzed,with a focus on identifying and examining the main quality problems and risks.Results The average pass rate of the sampling inspection in 2022 was 99.4% .The overall safety situation of China's post-marketing drug quality is stable and manageable,indicating that the drug quality is at a high level.Conclusions By carrying out exploratory studies related to drug safety,authenticity,and efficacy,national sampling plays an important role in comprehensively evaluating the quality status of drugs.It aids in improving the quality control level of drug varieties and industry standards,strengthening quality and safety supervision,combating illegal practices such as adulteration and falsification,and providing public warnings about drug safety.

【Objective】 To explore the current status and development trend of research on external therapies in traditional Chinese medicine (TCM) for insomnia over the past 10 years through bibliometrics and visual analysis, to provide references for further research on the topic. 【Methods】 Literature relating to TCM external therapies for insomnia from January 1, 2012 to December 31, 2021 was retrieved from Chinese databases, including China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and from the Web of Science Core Collection (WOSCC) for English articles. CiteSpace, VOSviewer, Scimago Graphica, and NoteExpress software were used to analyze publication volumes of the papers and how they were distributed in different journals, as well as to visualize the data of the countries, authors, institutions, and keywords. 【Results】 A total of 6 085 papers were obtained, of which 5 592 were from the Chinese databases and 493 were from the English database, with their publication volumes growing steadily year on year. Approximately 45 countries and regions were found to have published research on the topic. In terms of Chinese publications, the author with the most papers published was CHEN Yunfei from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine. The closest collaboration was between LIU Chengyong from the Affiliated Hospital of Nanjing University of Chinese Medicine and YUE Zenghui from Hunan University of Chinese Medicine. In terms of English publications, the author with the most papers published was MAO Junj from Sloan-Kettering Cancer Research Center, USA, and LAO Lixing from the University of Hong Kong was his closest partner in collaboration. Heilongjiang University of Chinese Medicine was the institution with the most Chinese publications, and Shanghai University of Traditional Chinese Medicine was the one with the most English papers published. Studies on the topic were published in 386 Chinese journals and 205 English journals, respectively. Nowadays, the clinical application of TCM external treatments for insomnia, the selection of meridians and acupoints, therapies for insomnia and its related diseases are research hotspots. The combined use of different TCM external therapies is a trend in the treatment of insomnia and its concomitant diseases, especially in the fields of oncology, nursing, and psychiatric disorders. The exploration of mechanisms of TCM external therapies for insomnia is also a key direction for future research. In clinical practice, the commonly used external therapies for insomnia include acupuncture, ear-acupressure with beans, acupoint application, etc. The commonly selected acupoints are auricular points, Sishencong (EX-HN1), Shenmen (HT7), etc. The frequently studied meridians are Ren, Du, Qiao, etc. The insomnia concomitant diseases are depression, stroke, anxiety, etc. 【Conclusion】 A wealth of research results have been accumulated in the treatment of insomnia by TCM external therapies, but authoritative research results are not so many. Therefore, institutions in different countries should strengthen communications and cooperation, and researchers should be encouraged to make innovations and breakthroughs on the basis of inherited TCM external therapies, so as to produce more valuable research results and improve TCM external therapies for providing better treatments for patients with sleep disorders.

This paper focused on the research progress of the assessment methods of carers′ fall concern for the elderly. The content of this review included the definition of carers′ fall concern, and the advantages and disadvantages of various assessment method of carers′ fall concern for the caregivers to the elderly, such as qualitative interviews, questionnaires, and scales. Through this review, the authors hoped to provide a reference for selecting or developing a localized carers′ fall concern assessment tool.

Objective:To explore the economic applicability and safetyof the novel uterovaginal pubic comb suspension(UPCS)surgery with Mersilene tape in the treatment of pelvic organ prolapse(POP).Methods:A ret-rospective analysis was conducted on the clinical data of patients who underwent UPCS surgery due to POP from January 1st,2021 to February 28,2023.They were divided to the UPCS surgery with Mersilene tape group(group A)and suspension surgery with Y-shaped mesh group(group B)respectively.The POP-Q indication points,sus-pension surgery duration,intraoperative bleeding volume,material expense,postoperative catheter retention time,anal exhaust time and hospitalization duration were recorded for both groupbefore and after surgery.Evaluate the severity of POP related symptoms in patients before and after surgery using the pelvic Floor Distress Invento-ry-short Form 20(PFDI-20)and Pelvic Organ Prolapsed/Urinary Incontinence Sexual Questionnaire-12(PISQ-12),and follow up and observe the patients and analyze the complications.Results:A total of 17 POP patients were included in the study.There were 12 patients in group A while 5 patients in group B.The suspension material expense of group A was considerably lower than that of group B(P＜0.05).There was no significant difference between the two groups in preoperative PFDI-20 score,preoperative PISQ-12 score,UPCS surgery duration,intr-aoperative bleeding volume,postoperative urinary catheter retention time,postoperative anal exhaust time and hospitalization duration.All patients showed stable vital signs during the surgery and no severe complications were reported.Compared with the preoperative status,the positions of the Aa,Ba,and C indicatorpoint in group A and group B were all increased significantly(P＜0.05).The PFDl-20 and PISQ-12 scores of the two groups at the last follow-up after surgery showed significant improvement compared to those before surgery(P＜0.05).No signifi-cant difference was found in the PFDI-20 and PISQ-12 scores between the two groups after surgery(P＞0.05).There were no significant differences in the postoperative complications between the two groups(P＞0.05).Con-clusions:Compared with suspension surgery with Y-shaped mesh,UPCS surgery with Mersilene tape is safe and effective in the treatment of POP.The UPCS surgery with Mersilene tape showed better cost-effectiveness in the treatment of POP,and the surgical steps are relatively simple.Therefore,UPCS surgery with Mersilene tape was worthy of promotion in clinical practice.