BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

In this paper， by consulting the ancient and modern literature， the name， origin， quality evaluation， harvesting and processing， and others of the original animal and medicinal materials of Moschus were systematically sorted out and verified， in order to provide the basis for the development and utilization of the famous classical formulas containing Moschus. According to the textual research， musk deer was first recorded in Shanhaijing. Shennong Bencaojing was recorded as Moschus and all generations were used as the correct name， but there were also aliases such as Shefu， Xiangzhang and Xiangqizi. In ancient times， Moschus berezovskii， M. sifanicus and M. moschiferus were the main sources of Moschus， and the quality of Moschus produced in northwest China was better than that produced in the Yangtze River basin. In modern times， Moschus of M. moschiferus produced in northeast China， M. sifanicus produced in Gansu， Sichuan and other places， and M. berezovskii produced in Ningxia， Shaanxi and other places are regarded as genuine. In ancient times， gunshots， lassoes， arrow shots and other methods were generally used to hunt live musk deer， and the sachets were immediately cut off. Those with high quality were called Xiangshanhuo， and dried in the shade after harvesting， which was known as Maoke Shexiang. Cut open the sachet， remove the shell and dry preservation， commonly known as Moschus kernel. In modern times， the method of taking Moschus from the living body of cultured musk deer is adopted， that is， Moschus kernel is directly taken from its sachet， dried in the shade or dried in a closed dryer. This method realizes the sustainable utilization of Chinese herbal medicine resources， but attention should be paid to the frequency and quality of Moschus. The harvesting time is mostly after the autumnal equinox every year， and before the next summer， it is better to gather sachet in winter. In recent times， it is believed that the shell Moschus is dry， full， thin， elastic， loose inside， many particles， strong and persistent aroma for the best， while the Moschus kernel is particle purple-black， powder yellow-brown， soft and oily texture， strong and persistent aroma for the best. The ancient processing method of Moschus was extracting kernels from the shell. After removing impurities， it is ground and used as medicine. Because its composition is not suitable for heating， the processing method is most common in preparations such as grinding into powder and putting into pills or powders， which has the effect of opening up the orifices and refreshing the mind， and it has continued to this day. Based on the research conclusions， it is suggested that the development of famous classical formulas containing Moschus， M. sifanicus， M. moschiferus and M. berezovskii should be used as the origins. According to the processing requirements specified in the original formula， it should be processed and used as medicine， while those without processing requirements should be used as raw products.

Objective To investigate the correlation between Yes-associated protein(YAP)nuclear expression and tumor size with prognosis of patients with epithelial ovarian cancer(EOC)and to study the role of YAP in EOC.Methods 120 patients with EOC were selected as the experimental group,including 38 patients with early stage(Ⅰ+Ⅱ)EOC and 8 2 patients with advanced stage(Ⅲ+Ⅳ)EOC.3 0 normal ovarian tissues obtained from patients with uterine leiomyoma were enrolled as the control group.Immunohistochemical(IHC)assay was em-ployed to determine YAP expression and sub-location.The relationship between YAP expression and the pathologi-cal parameters of the 120 patients with EOC was analyzed,so as to the prognosis of these patients.EOC cells(C13K and OV2008)were cultured with varying initial cell volumes.Ki67 expression and cell proliferation were tested by immunofluorescence and cloning assay respectively.YAP expression at mRNA and protein levels were de-tected by q-PCR and Western blot respectively when the cell conference of EOC cells reached to low(60％)and high(90％)cell density.Results The YAP nuclear expression was significantly higher in the EOC group com-pared to the control group(P＜0.05).The average diameter of stage Ⅰ+Ⅱ EOC was larger than that of stage Ⅲ+Ⅳ EOC(P＜0.01).The high nuclear expression of YAP was positively associated with pathological grade,clinical stage and the level of Ca125＞1 000 IU/ml,while negatively correlated with tumor size(all P＜0.05).Survival analyses showed that smaller tumor size(＜10 cm)and higher YAP nuclear expression were negatively as-sociated with the 3-year overall survival rate of EOC patients(P＜0.01).C13K and OV2008 cells cultured in the low density group exhibited a high number of clone formation,high Ki67 and YAP expression(P＜0.01).The down-regulation of YAP expression could decrease the cell viability of EOC cells in the low-and high-density groups(P＜0.05).Conclusion Higher level of YAP nuclear expression and smaller tumour size are inversely associated with the clinical prognosis of patients with EOC.Inhibiting YAP nuclear expression leads to a decrease in the prolif-eration capacity of EOC cells.

Objective The aim of this study was to screen and verify the proteins interacting with Vimentin,investigate the regulatory relationship between FABP5 and candidate proteins,and further explore the mechanism of FABP5 in hepatocellular carcinoma.Methods Immunoprecipitation combined with tandem mass spectrometry(IP-MS)was used to screen the proteins that bind to FABP5.The binding relationship between FABP5 and candi-date interacting proteins was verified from the exogenous and endogenous levels by Co-immune precipitation assay(Co-IP).RT-qPCR,Western blot and immunofluorescence were used to observe the effect of knockdown FABP5 on the transcription and translation of Vimentin in HCC cells.The effect of overexpressing FABP5 on the cytoskeleton of HCC cell was observed by phalloidin staining.Results 336 potential target proteins that bind to FABP5 were identi-fied through IP-MS.Based on literature,five candidate proteins related to tumors were selected,namely PRDX1,PRSS3,PKM,HSP90AA1,and Vimentin.The binding relationship between FABP5 and Vimentin protein was con-firmed through both exogenous and endogenous Co-IP.Knockdown FABP5 has no significant effect on the expression of Vimentin mRNA,but it can inhibit the expression of Vimentin protein,and overexpression of FABP5 can affect the cytoskeleton of HCC cell.Conclusions FABP5 promotes the migration and invasion of HCC cells by the regula-tion of Vimentin and the influence of cytoskeletal remodeling,and thus it is expected to be a potential target for anti-HCC and provide new ideas for the treatment of HCC.

Objective:To analyze the epidemiological and etiological characteristics of herpes pharyngitis (HA) in three prefectures of Jiangsu Province, and provide evidence for the prevention and control of HA in Jiangsu.Methods:Three surveillance sentinel hospitals in Wuxi, Suzhou and Yancheng were selected from May 2018 to December 2022, and information related to HA visits and hospitalized cases was regularly collected from the hospital inpatient management system by age groups. Enterovirus nucleic acid detection was performed by RT-PCR, and sequencing analysis, identification of genotype subtypes, and phylogenetic analysis were performed on the sequences of the gene encoding the coat protein VP1 of the main prevalent strains.Results:A total of 57 709 HA cases were recorded in the sentinel hospitals in in Wuxi, Suzhou and Yancheng, which was 1.76 times higher than the reported cases of hand, foot and mouth disease during the same period (57 709/32 831).The percentage of HA hospitalizations was 1.35% (781/57 709), and the percentage of hospitalizations showed an increasing trend from year to year ( χ2=62.79, P<0.001 ).The incidence peak of HA was during May-July. The cases were mainly children aged 12-59 months (67.07%, 38 708/57 709), with the highest case number in age group 36-59 months (34.40%, 19 852/57 709). The HA positivity rate was 33.82% (644/1 904); enterovirus A was predominant (54.04%, 348/644); of these, Coxsackievirus (CV)A6 accounted for the highest percentage (52.59%, 183/348), while CVA16 and CVA4 accounted for 24.71% (86/348) and 15.23% (53/348), respectively. All 10 CVA4 HA endemic strains belonged to the C2 gene subtype, and all 6 CVA6 HA endemic strains belonged to the D3a gene subtype; and were genetically closer to and related to the strains in some areas of China (Fujian Province, Guangzhou City, Jiangxi Province, Yunnan Province, Tianjin City, etc.). Conclusions:The disease burden of HA was heavy in 3 areas in Jiangsu, children in age group 12-59-month were mainly affected, and the annual incidence peak of HA was during May-July. The pathogens causing HA varied, but predominated by enterovirus A and had low intra-typical differentiation, and no new evolutionary branches were found, suggesting that it is necessary to include HA in foot and mouth disease surveillance or regarded as a notifiable communicable disease.

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.

Objective To explore the influence of IL-6 secreted by cancer-associated fibroblasts(CAFs)on pro-moting the proliferation and invasion of ovarian cancer cells and the possible mechanisms.Methods CAFs and normal ovarian fibroblasts(NFs)were isolated and cultured respectively from epithelial ovarian cancer and normal ovarian epithelial tissues.Cell markers alpha-smooth muscle actin(α-SMA),E-cadherin were detected by West-ern blot and immunofluorescence.CAFs and normal ovarian fibroblasts(NFs)were collected and cultured,and their supernatants were used to establish an indirect co-culture system with ovarian cancer SKOV3 cells,including SKOV3 cells alone(SKOV3)group,SKOV3 combined with the supernatants of NFs(NFs)group and SKOV3 combined with the supernatants of CAFs(CAFs)group.Cell immunochemistry was used to detect the expression of alcohol dehydrogenase 1B(ADH1B)in SKOV3 cells co-cultured with the supernatant of CAFs or NFs.Before and after treatment with the methylation inhibitor 5-aza-2'-deoxycytidine(5-Aza-dC),methylation-specific PCR(MSP),Reverse transcription quantitative real-time PCR(RT-qPCR),enzyme-linked immunosorbent assay(ELISA),and Western blot were used to detect the mRNA level and methylation status of ADH1B,and the phos-phorylation level of signal transducers and activators of transcription 3(p-STAT3).The cell counting kit-8(CCK-8)method and Transwell assay were used to investigate the effects of the IL-6 inhibitor LMT-286 and recombinant human interleukin-6(rhIL-6)on cell proliferation and invasion.Results The protein levels of α-SMA was highly expressed,however,CAFs and NFs cells almost lacked the E-cadherin protein.Compared with the SKOV3 and NFs groups,CAFs group exhibited significantly downregulated mRNA and protein expression of ADH1B.After treatment with 5-Aza-dC,ADH1B methylation was partially reversed,and the mRNA and protein expression of ADH1B increased in all groups.The phosphorylation level of STAT3 proteins was significantly reduced in CAFs group,while there were no significant changes in SKOV3 and NFs groups.Intervention with LMT-286 and rhIL-6 only inhibited or promoted the proliferation and invasion of cells in CAFs group,while there were no significant changes in SKOV3 and NFs groups.Conclusion CAFs can enhance the methylation of ADH1B in ovarian cancer cells via IL-6/STAT3 pathway,and may promote the proliferation and invasion.

In April 2024, the World Health Organization/International Agency for Research on Cancer (IARC) published the global cancer statistics 2022 in the CA: Cancer Journal for Clinicians. This report focuses on the incidence and mortality of 36 cancers in 185 countries or territories worldwide, analyzing the differences of gender, geographic region, and the Human Development Index (HDI) level. It is estimated that in the year 2022, there were 19.96 million new cancer cases and 9.74 million cancer deaths worldwide. Lung cancer (2 480 301, 12.4%) was the most frequently diagnosed cancer in 2022, followed by female breast cancer (2 295 686, 11.5%), colorectal cancer (1 926 118, 9.6%), prostate cancer (1 466 680, 7.3%), and gastric cancer (968 350, 4.9%). Lung cancer (1 817 172, 18.7%) was also the leading cause of cancer death, followed by colorectal cancer (903 859, 9.3%), liver cancer (757 948, 7.8%), female breast cancer (665 684, 6.9%), and gastric cancer (659 853, 6.8%). With demographics-based predictions indicating that the number of new cases of cancer will reach over 35 million by 2050. The Beijing Office for Cancer Prevention and Control team has collated this report and briefly interpreted it in combination with the current situation of cancer incidence and mortality in China.

ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action， so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group， model group， carbamazepine group （0.06 g·kg^-1·d^-1）， high-dose Lutongning group （2.70 g·kg^-1·d^-1）， and low-dose Lutongning group （1.35 g·kg^-1·d^-1） according to the stratified basic mechanical pain thresholds， with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg^-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin （HE） staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors interleukin （IL）-1， IL-6， IL-8， tumor necrosis factor （TNF）-α， neuropeptide substance P， and β-endorphins （β-EP） in the serum of rats， and Western blot was used to detect the protein expression levels of IL-1β， purinergic receptor P2X7 （P2X7R）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）. ResultCompared with that in the normal group， the pain threshold of rats in the model group was significantly lower （P<0.01）. The absolute value of neutrophils （NEUT#） and the percentage of neutrophils （NEUT） were significantly improved， and the percentage of lymphocytes （LYMPH） was significantly reduced （P<0.01）. The serum levels of IL-1， IL-6， IL-8， and TNF-α were significantly increased （P<0.01）. SP content in brain tissue was significantly increased， and β-EP content was significantly decreased （P<0.01）. The relative protein expression of IL-1β， P2X7R， and p-p38 MAPK was significantly increased （P<0.05）. HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration， mild proliferation of microglial cells， reduction in the number of myelinated nerves， and obvious demyelination. The trigeminal nerve fibers of rats were disarranged， and some nerve fibers showed vacuolization. Axons were swollen， and Schwann cells proliferated. Demyelination was observed. Compared with the model group， each administration group significantly increased the pain threshold of rats （P<0.05， P<0.01）， reduced NEUT# and NEUT， and elevated LYMPH （P<0.05， P<0.01）. The administration group significantly decreased the levels of IL-1， IL-6， IL-8， and TNF-α in serum and SP in brain tissue （P<0.01） and increased the level of β-EP （P<0.01）. They significantly down-regulated the protein expression of IL-1β， P2X7R， and p-p38 MAPK（P<0.05， P<0.01） and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats， and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.

Objective:To investigate the clinical outcomes and efficacy of trabecular metal (TM) cones for the reconstruction of metaphyseal bone defects in revision total knee arthroplasty.Methods:A retrospective analysis was conducted on 46 patients (47 knees), who underwent revision total knee arthroplasty with TM cones for metaphyseal defect reconstruction from July 2015 to August 2023. The cohort comprised 12 males and 34 females, ranging from 41 to 83 years of age, with a mean of 68.65 ± 9.09 years. Body mass index (BMI) ranged from 19.5 to 36.0 kg/m 2, averaging 27.20±4.50 kg/m 2. Bone defects were stratified according to the Anderson Orthopedic Research Institute (AORI) classification, including 64 sides (AORI T2B type 20 sides, T3 type 16 sides, F2B type 11 sides, F3 type 17 sides) which were addressed with 67 cones. Evaluations during follow-up included range of motion (ROM), visual analogue scale (VAS) for pain, and the American Knee Society Score (KSS). Long leg radiographs and knee X-rays were reassessed for femorotibial angle (FTA) and joint alignment, osseointegration of the TM cones, and any complications were documented. Results:The average follow-up duration was 46.22±26.55 months (range 16-103 months). The KSS knee score significantly improved from 29.22±19.79 preoperatively to 88.22±6.01 at the final follow-up ( F=258.118, P<0.001). Similarly, the KSS function score saw a marked increase from a preoperative average of 7.65±8.21 to 56.30±6.10 at the final follow-up ( F=354.711, P<0.001). VAS scores significantly decreased from 5.35±1.50 preoperatively to 0.28±0.50 at the final follow-up ( F=300.934, P<0.001). ROM improved from 67.72°±34.62° preoperatively to 85.33°±9.15° at the final follow-up ( F=7.798, P<0.001), and the FTA improved from 179.24°±10.30° preoperatively to 174.39°±1.69° at the final follow-up, a statistically significant enhancement ( F=9.123, P<0.001). Osseointegration was observed in 95.5% of the cases (64/67 cones). There were no instances of osteolysis or aseptic loosening observed, indicating stable prosthetic fixation. Complications were minimal, with one reported case of a femoral shaft fracture, which was successfully treated with internal fixation, resulting in satisfactory healing at 6 months. At the last follow-up (3 years after operation), the patient could walk at home with a walker and the other patients had no complications such as periprosthetic joint infection, dislocation and periprosthetic fracture. Conclusion:The application of trabecular metal cones in revision total knee arthroplasty provides an effective solution for the reconstruction of severe metaphyseal bone defects, enhancing prosthetic stability and restoring the knee joint's mechanical alignment. The trend towards successful osseointegration in the TM cones is promising, and a significant improvement in knee joint function has been observed.