BACKGROUND: Growing evidence suggests that long non-coding RNAs (lncRNAs) exert pivotal roles in fostering chemoresistance across diverse tumors. Nevertheless, the precise involvement of lncRNAs in modulating chemoresistance within the context of gallbladder cancer (GBC) remains obscure. This study aimed to uncover how lncRNAs regulate chemoresistance in gallbladder cancer, offering potential targets to overcome drug resistance. METHODS: To elucidate the relationship between gemcitabine sensitivity and small nucleolar RNA host gene 1 ( SNHG1 ) expression, we utilized publicly available GBC databases, GBC tissues from Renji Hospital collected between January 2017 and December 2019, as well as GBC cell lines. The assessment of SNHG1, miR-23b-3p, and phosphatase and tensin homolog (PTEN) expression was performed using in situ  hybridization, quantitative real-time polymerase chain reaction, and western blotting. The cell counting kit-8 (CCK-8) assay was used to quantify the cell viability. Furthermore, a GBC xenograft model was employed to evaluate the impact of SNHG1 on the therapeutic efficacy of gemcitabine. Receiver operating characteristic (ROC) curve analyses were executed to assess the specificity and sensitivity of SNHG1. RESULTS: Our analyses revealed an inverse correlation between the lncRNA SNHG1 and gemcitabine resistance across genomics of drug sensitivity in cancer (GDSC) and Gene Expression Omnibus (GEO) datasets, GBC cell lines, and patients. Gain-of-function investigations underscored that SNHG1 heightened the gemcitabine sensitivity of GBC cells in both in vitro and in vivo  settings. Mechanistic explorations illuminated that SNHG1 could activate PTEN -a commonly suppressed tumor suppressor gene in cancers-thereby curbing the development of gemcitabine resistance in GBC cells. Notably, microRNA (miRNA) target prediction algorithms unveiled the presence of miR-23b-3p binding sites within SNHG1 and the 3'-untranslated region (UTR) of PTEN . Moreover, SNHG1 acted as a sponge for miR-23b-3p, competitively binding to the 3'-UTR of PTEN , thereby amplifying PTEN expression and heightening the susceptibility of GBC cells to gemcitabine. CONCLUSION The SNHG1/miR-23b-3p/PTEN axis emerges as a pivotal regulator of gemcitabine sensitivity in GBC cells, holding potential as a promising therapeutic target for managing GBC patients.
Humans ; Deoxycytidine/pharmacology* ; PTEN Phosphohydrolase/genetics* ; Gemcitabine ; RNA, Long Noncoding/metabolism* ; MicroRNAs/genetics* ; Gallbladder Neoplasms/genetics* ; Cell Line, Tumor ; Animals ; Mice ; Drug Resistance, Neoplasm/genetics* ; Mice, Nude ; Antimetabolites, Antineoplastic ; Gene Expression Regulation, Neoplastic

OBJECTIVE: To compare clinical effect of arthroscopic double row fixation and single row fixation in treating Ideberg typeⅠA scapular glenoid fracture. METHODS: From June 2018 to December 2022, 26 patients with Ideberg typeⅠA scapular glenoid fracture treated with shoulder arthroscopy were divided into single-row anchor group and double-row anchor group according to the fixation method of fracture block. There were 12 patients in single-row anchor group, including 7 males and 5 females, aged from 25 to 53 years old with an average of (38.42±9.61) years old;the time from injury to operation ranged from 2 to 7 days with an average of (4.75±1.82) days. There were 14 patients in double-row anchor group, including 10 males and 4 females, aged from 21to 53 years old with an average of (37.36±10.19) years old;the time from injury to operation ranged from 1 to 8 days with an average of (4.21±2.01) days. The changes of shoulder joint flexion, abduction, lateral lateral rotation, Constant-Murley shoulder function score and Rowe scores were compared between two groups before operation and 1 year after operation. The percentage of bone mass in pelvis area before operation and the percentage of bone defect in pelvis area at the latest follow-up were compared between two groups. RESULTS: All patients were followed up for 12 to 15 months with an average of (13.08±1.17) months in single-row anchor group and 12 to 15 months with an average of (13.29±1.07) months in double-row anchor group, with no statistical significance between two groups (P>0.05). The results of anterior flexion, abduction and lateral lateral rotation in single-row anchor group were(86.67±6.62) °, (79.50±5.68) °, (38.17±1.70) ° before operation, and (162.50±4.52)°, (169.17±3.35)°, (50.67±10.20)° at 1 year after operation; while in double-row anchor group were (84.14±5.48) °, (81.71±5.20) °, (39.29±3.63) ° before operation and (162.29 ± 5.53) °, (167.14±3.61) °, (56.93±9.56) ° at 1 year after operation;the difference between two groups before operation and 1 year after operation was statistically significant (P<0.05). There were no significant difference between two groups (P>0.05). Constant-Murley scores and Rowe scores in single-row anchor group were (55.42±3.75), (43.75±18.49) before operation and (94.83±2.21), (95.42±4.50) at 1 year after operation, respectively;while in double-row anchor group were (54.50±7.88), (41.79±18.25) before operation and (94.36±4.73), (95.00±4.80) at 1 year after operation;there was no significant difference in Constant-Murley score and Rowe score between two groups before operation and 1 year after operation (P>0.05). There was significant difference in the percentage of bone mass in pelvis area between two groups before operation (P>0.05). There was no significant difference in the percentage of bone defect in the shoulder area between single-row anchor group(4.42±1.51)% and double-row anchor group (2.71±1.44)% at 1 year after operation (P<0.05). CONCLUSION Both single and double row fixation techniques for the treatment of Ideberg typeⅠA scapular glenoid fracture could receive satisfactory functional recovery. However, double-row fixation has more advantages in reducing bone resorption of fracture mass.
Humans ; Female ; Male ; Middle Aged ; Arthroscopy/methods* ; Adult ; Scapula/surgery* ; Case-Control Studies ; Fractures, Bone/physiopathology* ; Fracture Fixation, Internal/methods* ; Shoulder Joint/physiopathology* ; Range of Motion, Articular

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective To explore the effect of open reading frame 66(C12ORF66)located at chromosome 12 on the viability of MYCN amplified NB cell lines.Methods DDatasets GSE16476 and GSE49710 in R2 database were analyzed for expression level of C12ORF66 in MYCN amplified and MYCN non-amplified NB cells and its potential correlation with the prognosis of pediatric patients.C12ORF66 mRNA expression level in normal tissue immortalized cell lines,MYCN amplified and MYCN non-amplified cell lines were detected by RT-qRCR.Transient or stable knockdown of C12ORF66 cell lines were constructed to compare the difference in real time cellular analysis(RTCA),colony formation,Ki67 positive cells between the control group and the C12ORF66 knockdown group.Results By analyzing R2 datasets,C12ORF66 level in MYCN amplified samples was significantly higher than that in MYCN non-amplified samples,and the expression of C12ORF66 was negatively correlated with the prognosis of pediatric patients(P＜0.05).C12ORF66 highly expressed in MYCN-amplified BE(2)-C and SK-N-BE(2)cell lines than in MYCN non-amplified CHLA-255 and SH-SY5Y cell lines(P＜0.001).Transient or stable knockdown of C12ORF66 resulted in significant slow down of proliferation of MYCN amplified NB cells(P＜0.001),the colony formation ability was significantly reduced(P＜0.001),and the proportion of Ki67 positive cells was significantly decreased(P＜0.05).Conclusions C12ORF66 was highly expressed in MYCN amplified clinical NB samples and cell lines which is believed to be correlated with poor prognosis of pediatric patients.C12ORF66 knockdown signifi-cantly inhibits cell viability of NB cells.

Objective:To investigate the clinical effect of progressive transfer of penile flap combined with local scrotal flap in correction of severe concealed penis in children.Methods:The clinical data of children with severe concealed penis admitted to the Children’s Hospital Affiliated to Zhengzhou University from July 2021 to July 2023 were retrospectively analyzed. The concealed penis was corrected by progressive transfer of penile flap combined with local scrotal flap. During the operation, a small amount of excess inner prepuce was removed and the outer prepuce was cut in the middle of the dorsal side of the penis. Then the penile flap was transferred from dorsal to ventral, gradually covering the wound without tension. The local scrotal flap was lifted upwards and sutured to the frenulum for covering the ventral foreskin defect of the penis. The amount of blood loss during the operation was recorded. The pain tolerance, the duration of prepuce edema, the length of penis extension and the healing of skin flap were observed. The appearance of the penis was followed up to observe whether the penis was retracted, and the satisfaction of the children and their guardians was recorded.Results:A total of 32 male children were enrolled, ranging in age from 3 to 10 years, with an average age of 7.2 years. The penis of all the children had a conical appearance, and the penile shaft was buried under the subcutaneous anterior pubis, which was difficult to palpate in its natural state. The average intraoperative blood loss was about 5 ml. All patients had pain after the operation. Two patients needed a pump to relieve pain, and the rest could tolerate it after rectum administration of indomethacin suppositories. The edema of the prepuce was mild after the operation, and the edema basically disappeared when the patient was discharged 7-9 days later. The penis could be lengthened by 1.5-3.0 cm under static conditions, averaging about 2.0 cm. After surgery, only 1 patient had a small area (about 5 mm × 4 mm) of infection in the scrotal flap and poor incision healing, and scar healing after dressing change and intensive nursing. The other flaps healed well. After 6 to 12 months of follow-up, the penis length of 2 cases was slightly retracted from the time of discharge, and the remaining 30 cases had no significant change. The patients and their guardians were satisfied with the operation results.Conclusion:The progressive transfer of penile flap combined with local scrotal flap correction of severe concealed penis in children can fully lengthen the penile body, and the degree of postoperative retraction is low, the appearance of the penis is good, and the patient satisfaction is high.

Biomaterials have gained substantial attention in the field of regenerative medicine and shown respectable potential in clinical translation. However, the function of biomaterials is hindered by the fibrotic encapsulation of foreign body response (FBR) under some circumstances. FBR also lowers the expected service life of implanted devices and causes pain, distortion of tissue or even malignant diseases. Therefore, the mechanism of FBR and the modulating factors need to be further investigated to improve the tissue biocompatibility of biomaterials. This article reviewed the process of FBR, summarized the properties and modification of biomaterials related to FBR, and discussed strategies to mitigate this immune reaction.

Objective:To analyze the epidemiological characteristics and economic burden of palmoplantar pustulosis (PPP) in China.Methods:A population-based retrospective study was conducted using the data from China′s Urban Basic Medical Insurance data from January 1, 2012, to December 31, 2016. International Classification of Diseases code and diagnoses in Chinese for PPP were used to identify cases and estimate the prevalence, incidence, and cost. Subgroup analyses were performed according to age and sex, and sensitivity analyses were conducted to evaluate the robustness of the results. Age-adjusted prevalence rates were calculated based on the 2010 national census data.Results:The crude prevalence and incidence rate of PPP in 2016 were 2.730/100 000 (95% CI: 2.218/100 000-3.242/100 000) and 1.556/100 000 (95% CI: 1.154/100 000-1.958/100 000), and the prevalence rate of females (2.910/100 000) was higher than that of males (2.490/100 000, χ2=97.48, P=0.001). The incidence rate of females (1.745/100 000) was also higher than that of males (1.418/100 000, χ2=85.02, P=0.001). The age peak of incidence and prevalence of patients with PPP was in the 30-39-year age group and a small peak existed in the 0-3-year age group among people under 20 years old. From 2012 to 2016, the average number of visits was (2.44±0.04) per patient, and the total per-capita cost per year was (982.40±39.19) yuan. Conclusion:In 2016, the prevalence and incidence rate of PPP in China were higher in females than in males, and the highest age peak was in the 30-39-year age group.

Objective:To investigate the function and underlying mechanism of cysteine and glycine-rich protein 2(CSRP2)in neuroblastoma(NB).Methods:The correlation between the expression level of CSRP2 mRNA and the prognosis of NB children in NB clinical samples was analyzed in R2 Genomics Analysis and Visualization Platform.The small interfering RNA(siRNA)targeting CSRP2 or CSRP2 plasmid were transfected to NB cell lines SK-N-BE(2)and SH-SY5Y.Cell proliferation was observed by crystal violet staining and real-time cellular analysis.The ability of colony formation of NB cells was ob-served by colony-forming unit assay.Immunofluorescence assay was used to detect the expression of the proliferation marker Ki-67.Flow cytometry analysis for cell cycle proportion was used with cells stained by propidium iodide(PI).Annexin V/7AAD was used to stain cells and analyze the percentage of cell apoptosis.The ability of cell migration was determined by cell wound-healing assay.The level of protein and mRNA expression of CSRP2 in NB primary tumor and NB cell lines were detected by Western blot and quantitative real-time PCR(RT-qPCR).Results:By analyzing the NB clinical sample databases,it was found that the expression levels of CSRP2 in high-risk NB with 3/4 stages in international neuroblas-toma staging system(INSS)were significantly higher than that in low-risk NB with 1/2 INSS stages.The NB patients with high expression levels of CSRP2 were shown lower overall survival rate than those with low expression levels of CSRP2.We detected the protein levels of CSRP2 in the NB samples by Western blot,and found that the protein level of CSRP2 in 3/4 INSS stages was significantly higher than that in 1/2 INSS stages.Knockdown of CSRP2 inhibited cell viability and proliferation of NB cells.Overexpression of CSRP2 increased the proliferation of NB cells.Flow cytometry showed that the proportion of sub-G1,G0/G1 and S phase cells and Annexin V positive cells were increased after CSRP2 deficiency.In the cell wound-healing assay,the healing rate of NB cells was significantly attenuated after knockdown of CSRP2.Further mechanism studies showed that the proportion of the proliferation marker Ki-67 and the phospho-rylation levels of extracellular signal-regulated kinases 1/2(ERK1/2)were significantly decreased after CSRP2 knockdown.Conclusion:CSRP2 is highly expressed in high-risk NB with 3/4 INSS stages,and the expression levels of CSRP2 are negatively correlated with the overall survival of NB patients.CSRP2 significantly increased the proliferation and cell migration of NB cells and inhibited cell apoptosis via the activation of ERK1/2.All these results indicate that CSRP2 promotes the progression of NB by activating ERK1/2,and this study will provide a potential target for high-risk NB therapy.