Ubiquitination is a crucial post-translational modification process that can degrade proteins within cells and plays a vital role in maintaining protein homeostasis and abundance.Deubiquitinating enzymes(DUBs)are important proteases in the ubiquitin system.They reverse the ubiquitination process by cleaving protein chains and recycling ubiquitin molecules to regulate protein stability.Abnormal deubiquitinating enzyme activity is related to the occurrence and development of many malignant tumors.JOSD2,a DUB,is a member of the Machado-Joseph disease protein domain protease(MJD)family and characterized by a single highly conserved catalytic Josephin domain.Increasing studies have revealed a connection between JOSD2 and malignant tumors.This article elaborates on the current research status of DUBs,particularly JOSD2,in malignant tumors.Results suggest that JOSD2 is a potential target for the treatment of malignant tumors.

Objective:To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma.Methods:This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis.Results:A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups ( P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group ( P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ 2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ 2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death ( P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion:The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

Objective:To investigate the role and the mechanism of Ras-associated binding protein23 (RAB23) in the migration and invasion of esophageal squamous cell carcinoma (ESCC) cells.Methods:RAB23 mRNA levels were measured in 16 pairs of ESCC and adjacent normal tissues via real-time polymerase chain reactions. RAB23 mRNA levels in the ESCC and adjacent normal tissues of dataset GSE20347 deposited in the Gene Expression Omnibus (GEO) database were also analyzed. Immunohistochemistry (IHC) was used to detect the RAB23 protein expressions in 106 pairs of ESCC and adjacent normal tissues, as well as in the lymph glands and primary tumor tissues of 33 patients with positive lymph nodes and 10 patients with negative lymph nodes. Endogenous RAB23 expression was transiently depleted using siRNAs (si-NC, si-RAB23-1, and si-RAB23-9) or stably reduced using shRNAs (sh-NC and sh-RAB23) in ESCC KYSE30 and KYSE150 cells, and the knockdown efficiency was tested using Western blot assays. Cell counting kit-8 assays and mouse xenograft models were used to test the proliferation of ESCC cells . Transwell assays and tail vein-pulmonary metastasis models in immunocompromised mice were used to examine the migration and invasion of ESCC cells. Cell adhesion assays were used to test the adhesion of ESCC cells. RNA-seq assays were used to analyze how RAB23 knockdown influenced the expression profile of ESCC cells and the implicated signal pathways were confirmed using Western blot assays. Results:The RAB23 mRNA expression in 16 cases of ESCC tissues was 0.009 7±0.008 9, which was markedly higher than that in adjacent normal tissues (0.003 2±0.003 7, P=0.006). GEO analysis on RAB23 expressions in ESCC and adjacent normal tissues showed that the RAB23 mRNA level in ESCC tissues (4.30±0.25) was remarkably increased compared with their normal counterparts (4.10±0.17, P=0.037). Among the 106 pairs of ESCC and tumor-adjacent normal tissues, 51 cases exhibited low expression of RAB23 and 55 cases showed high expression of RAB23, whereas in the paired tumor-adjacent normal tissues 82 cases were stained weakly and 24 strongly for RAB23 protein. These results indicated that RAB23 expression was markedly increased in ESCC tissues ( P<0.001). Additionally, only 1 out of 33 primary ESCC tissues with positive lymph nodes showed low RAB23 protein expression. On the other hand, 7 samples of primary ESCC tissues with negative lymph nodes were stained strongly for RAB23 while its level in the other 3 samples was weak. These results showed that RAB23 expression was remarkably increased in primary ESCC tissues with positive lymph nodes compared with those with negative lymph nodes ( P=0.024). Further tests showed that 32 out of 33 positive lymph nodes were stained strongly for RAB23, whereas no negative lymph nodes ( n=10) exhibited high expression of RAB23 ( P<0.001). Both transient and stable knockdown of endogenous RAB23 expression failed to cause detectable changes in the proliferation of KYSE30 cells in vitro and in vivo, but attenuated the migration and invasion of KYSE30 cells as well as the invasion of KYSE150 cells. RAB23 knockdown was found to significantly decrease the number of adhesive KYSE30 cells in the sh-RAB23 group (313.75±89.34) compared with control cells in the sh-NC group (1 030.75±134.29, P<0.001). RAB23 knockdown was also found to significantly decrease the number of adhesive KYSE150 cells in the sh-RAB23 group (710.5±31.74) compared with the number of control cells in the sh-NC group (1 005.75±61.09, P<0.001). RNA-seq assays demonstrated that RAB23 knockdown using two siRNAs targeting RAB23 mRNA markedly impaired focal adhesion-related signal pathways, and decreased the levels of phosphorylated FAK (p-FAK) and phosphorylated paxillin (p-paxillin) in KYSE30 and KYSE150 cells. Conclusions:Significantly increased RAB23 in ESCC tissues positively correlates with lymph node metastasis. Depleted RAB23 expression attenuates focal adhesion-related signal pathways, thus impairing the invasion, metastasis, and adhesion of ESCC cells.

Objective:To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs).Methods:There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients.Results:In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference ( P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant ( P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference ( P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions:Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

Objectives:To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms.Methods:Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT).Results:Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated ( r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 ( r=-0.167, P=0.044), the level of serum CEA ( r=-0.061, P=0.032), and the level of serum ALT (r=-0.147, P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 ( r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT ( r=0.164, P=0.029). Conclusion:Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

Objective:To analyze the ultrasonic features of tonsillar lymphoma to improve the diagnostic accuracy.Methods:The clinical, pathological and ultrasonic data of nine patients with tonsillar lymphoma confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital during June 2015 and June 2022 were analyzed retrospectively, and the characteristics of their ultrasonic images were summarized.Results:All 9 cases of tonsil lymphoma were unilateral tonsil disease, including 4 cases on the left side and 5 cases on the right side. The average maximum diameter of tonsil lymphoma in 9 cases was 4.32 cm. There were 3 cases with simultaneous involvement of tonsil and cervical lymph nodes, all of which were ipsilateral lymph nodes. Gray scale ultrasound showed that the lesions were hypoechoic, with clear boundaries in 7 cases and unclear boundaries in 2 cases. The shape was full and irregular in 5 cases and oval in 4 cases. The echo was uniform in 7 cases and uneven in 2 cases. Color Doppler ultrasonography showed abundant internal blood flow signal in 1 case, a little dotted linear internal blood flow signal in 5 cases, and no obvious internal blood flow signal in 3 cases.Conclusions:The ultrasonic features of tonsillar lymphoma include hypoechoic area, clear boundary, full shape, irregular and uniform internal echo, no or low linear signal of internal blood flow. Ultrasonography is of great value in the diagnosis of this disease and can help clinical decision-making.

NUT carcinoma(nuclear protein in testis carcinoma)is a rare and highly invasive malignant tumor,which is most common in midline organs and lungs.The characteristic genetic change of NUT carcinoma is the rearrangement of NUT middle carcinoma family member 1(NUTM1)gene.In this article,we will review the pathogenic mechanism of its most common fusion form,bromodomaincontaining protein 4(BRD4)-NUTM1 fusion gene,and the progress in the research and development of targeting drugs.

At present,the incidence and mortality rates of lung cancer rank top among malignant tumors.The early diagnosis,treatment and drug resistance of lung cancer still remain as problems in the management of lung cancer.Researchers are dedicated to identifying reliable biomarkers as predictive indicators or effective therapeutic targets for lung cancer.Insulin resistance(IR),a disorder characterized by reduced biological activity of insulin,leads to increased insulin secretion.In recent years,more and more studies have revealed the association between IR and the occurrence and development of cancer,with the insulin/insulin-like growth factor signaling pathway possibly playing a crucial role.In this article,we will focus on the rela-tionship between IR and lung cancer,explore the impact and mechanism of IR on the development,progression and drug resis-tance of lung cancer.It may guide the development of new predictive tools and therapeutic strategies,and provide new ideas for research dedicated to reducing the incidence and mortality of lung cancer.

Objective To investigate the use and application trend of antibiotics in a cancer hospital in Tianjin,so as to provide reference for the rational clinical use of antibiotics.Methods The related data of antibiotics in the hospital from January 2018 to January 2021 were selected,and the utilization rate,defined daily doses(DDDs)of drugs,antibiotics use density(AUD),defined daily cost(DDC)and ranking ratio(B/A)of antibiotics were statistically analyzed.Results In 2018-2021,the annual use of antibiotics,utilization rate of antibiotics and AUD showed a downward trend.The mean annual utilization rate of antibiotics was 22.42％,and the mean annual AUD was 26.79 DDDs/(100 person·d).The top three antibacterial drugs in terms of annual consumption and DDDs were cephalosporins,carbapenems and penicillins.The main antibacterial drugs at all levels were unrestricted.There were 6 antibacterial drugs with DDC＞100.Voriconazole had the highest DDC.The B/A of ciprofloxacin sodium chloride,moxifloxacin tablets,Latoxefin sodium,moxifloxacin sodium chloride was close to or equal t0 1,indicating that the synchronization of these antibacterial drugs was good.Conclusion In 2018-2021,the selection and use of antibiotics in the cancer hospital in Tianjin was reasonable,and the clinical application indicators met the national standards.

Objective:To evaluate the effect of ultrasound-guided subserratus anterior plane block on postoperative analgesia in patients un-dergoing laparoscopic radical gastrectomy.Methods:Sixty patients who underwent elective laparoscopic radical gastrectomy were enrolled between May 2022 and October 2023 at Tianjin Medical University Cancer Institute&Hospital.Patients were assigned into two groups us-ing a random number table method:the control(group C)and the ultrasound-guided serratus anterior plane block(SAPB)(group S).Patient-controlled intravenous analgesia(PCIA)was administered at the end of the surgery.After surgery,visual analogue scale(VAS)of static pain scores was evaluated at 1,6,12,24,and 48 hours.PCIA pump was started at the VAS pain score≥4 after surgery,and sufentanil 0.1μg/kg was intravenously injected when the efficacy was inadequate.The requirement for PCIA use,time to first postoperative anal exhaust,first postoperative out-of-bed activity,first oral intake,and the duration of hospitalization stay were recorded for the two groups.Results:VAS scores were significantly lower at postoperative 1,6,and 12 h in group S than in group C(P<0.05).Additionally,the number of effective uses of PCIA,and rescue analgesia were significantly lower in group S[(6.1±0.4)(2)]than in group C[(18.6±1.4)(17)](P<0.001).The time to first postoperative anal exhaust,first postoperative out-of-bed activity,first oral intake,and duration of hospital stay were shortened in group S than in group C(P<0.05).There were no significant differences in other parameters between these two groups.Conclusion:Ultrasound-guided SAPB can reduce postoperative pain and facilitate fast recovery in laparoscopic radical gastrectomy patients.