Objective:To observe the expression of CD36 in hepatocellular carcinoma tissues and cell lines, and to investigate the effects of CD36 on the proliferation and migration abilities of human hepatocellular carcinoma cell lines and human hepatocellular carcinoma cell xenograft models in nude mice.Methods:Differences in the expression levels of CD36 transcripts in 371 hepatocellular carcinoma and paracancerous tissues were analyzed based on information from The Cancer Genome Atlas (TCGA) database. Cancer tissues and corresponding paracancerous tissues of 48 hepatocellular carcinoma patients who were diagnosed and underwent surgical treatment at the Affiliated Hospital of Yangzhou University from January 2019 to February 2021 were prospectively collected, and the levels of CD36 mRNA in the tissues were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) method. Western blotting was used to detect CD36 protein levels in human hepatocellular carcinoma cell lines Huh7 and HCCLM3 and human normal liver cell line LO2. Plasmids containing CD36 interfering sequences and empty plasmids were transfected into Huh7 cells or HCCLM3 cells for sh-CD36 group and control group, respectively. The CCK-8 assay was used to detect the proliferation ability (expressed as absorbance value) of cells in each group at 0, 12, 24, 36, 48 and 60 h of culture, and the scratch healing assay and Transwell assay were used to detect the migration ability of cells in each group. The Huh7 cells of sh-CD36 group or control group were injected into the axillary subcutis of BALB/c nude mice, with 4 mice in each group, to construct nude mice models of human hepatocellular carcinoma xenografts; the long and short diameters of tumor were measured weekly after 1 week of inoculation, and the tumor volume was calculated. The nude mice were put to death after 5 weeks of inoculation, and the tumor specimens were collected and weighed; the tumor cell morphology was observed under the microscope, and the expressions of CD36 and Ki-67 proteins in the tumor tissues was detected by immunohistochemistry (IHC).Results:Analysis of the data from the TCGA database showed that the level of CD36 transcripts was higher in hepatocellular carcinoma tissues compared with that in paracancerous tissues (4.2±1.8 vs. 3.2±1.5, t = 2.28, P = 0.035). Tissues detection using qRT-PCR in 48 patients with hepatocellular carcinoma showed that the relative expression of CD36 mRNA in hepatocellular carcinoma tissues was higher than that in paracancerous tissues (0.76±0.26 vs. 0.48±0.23, t = 3.52, P < 0.001). Western blotting assay showed that CD36 protein level in Huh7 and HCCLM3 cells was higher than that in LO2 cells, which were (1.42±0.11) times and (1.68±0.16) times higher than LO2 cells, respectively (both P < 0.001). At the mRNA and protein levels, the CD36 of Huh7 and HCCLM3 cells in the sh-CD36 group was lower than that in the corresponding control group (both P < 0.001). CCK-8 assay showed that the proliferative ability of Huh7 cells and HCCLM3 cells in the sh-CD36 group was lower than that in the corresponding control group after 36 and 24 h of culture (both P < 0.01). Scratch healing assay showed that the scratch healing rates of Huh7 cells [(12±3)% vs. (30±5)%, t = 4.01, P < 0.001] and HCCLM3 cells [(15±4)% vs. (29±5)%, t = 4.16, P < 0.001] in the sh-CD36 group were lower than those in the corresponding control group at 48 h of culture; Transwell assay showed that the number of Huh7 cells [(46±6) cells/field of view vs. (88± 6) cells/field of view, t = 5.56, P < 0.001] and HCCLM3 cells [(42±5) cells/field of view vs. (82±7) cells/field of view, t = 5.34, P < 0.001] penetrating into the membrane in 24 h in the sh-CD36 group was less than that in the corresponding control group. Five weeks after subcutaneous injection, the tumor volume [(682±268) mm 3vs. (1 375±512) mm 3, t = 4.73, P = 0.006] and tumor mass [(432±95) mg/mouse vs. (871±109) mg/mouse, t = 6.57, P < 0.001] of nude mice injected with Huh7 cells of the sh-CD36 group were lower than those of nude mice injected with Huh7 cells of the control group; under the microscope, the density of tumor cells in transplanted tumor specimens of nude mice injected with Huh7 cells of the sh-CD36 group was lower than that in nude mice injected with Huh7 cells of the control group, and the expression levels of both CD36 and Ki-67 proteins were also low. Conclusions:CD36 expression is up-regulated in cancer tissues of hepatocellular carcinoma patients and human hepatocellular carcinoma cell lines Huh7 and HCCLM3, and it may associate with cell proliferation and migration of hepatocellular carcinoma. Knockdown of CD36 expression significantly inhibits the proliferation and migration abilities of hepatocellular carcinoma cells in vitro, and inhibits the tumors of human hepatocellular carcinoma cell xenograft models in nude mice.

Objective:To compare the antiosteoporosis effect of conventional treatment and conventional treatment combined with Denosumab after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 211 patients with OVCF admitted to the Second Affiliated Hospital of Soochow University from September 2020 to September 2022. All the patients were female, aged 56-90 years [(71.4±8.1)years]. The bone mineral density T-score of the lumbar spine was (-2.6±1.0)SD before operation. Fracture segments included T 1-T 9 in 45 patients, T 10-L 2 in 146, and L 3-L 5 in 69. Of all, 174 patients were treated with single-segment surgery, 25 with two-segment surgery and 12 with surgery involving three or more segments. According to the wishes of the patients, 107 patients were treated with daily oral administration of calcium and active Vitamin D after PKP (conventional treatment group) and 104 patients with Denosumab combined with the conventional treatment after PKP (Denosumab therapy group). The bone mineral density T-scores of the lumbar spine of the two groups were compared before surgery and at the last follow-up. The visual analogue scale (VAS) and Oswestry disability index (ODI) before surgery, at 3 days, 6 months after surgery, and at the last follow-up were evaluated and the refracture rate after surgery was detected. Possible adverse effects after medication during anti-osteoporosis treatment were observed in two the groups. Results:All the patients were followed up for 12-24 months [(13.5±2.0)months]. Before surgery, the bone mineral density T-score of the lumbar spine was (-2.7±1.1)SD in the Denosumab therapy group and (-2.5±0.8)SD in the conventional treatment group ( P>0.05). At the last follow-up, the bone mineral density T-score of the lumbar spine was (-2.1±1.1)SD in the Denosumab therapy group, significantly higher than (-2.5±0.9)SD in the conventional treatment group ( P<0.05). In the Denosumab therapy group, the bone mineral density T-score of the lumbar spine at the last follow-up was significantly increased compared to that before surgery ( P<0.01), while there was no significant difference in the conventional treatment group ( P<0.05). Before surgery and at 3 days after surgery, the VAS scores and ODI values were (8.5±0.9)points, (2.8±0.8)points, 48.7±4.8 and 25.6±4.0 in the Denosumab therapy group, which was not statistically different from those in the conventional treatment group [(8.5±1.3)points and (2.8±0.9)points, 47.9±7.0 and 25.9±3.7] ( P>0.05). At 6 months after surgery and at the last follow-up, the VAS scores and ODI values were (2.2±0.8)points, (1.7±0.8)points, 24.2±3.6 and 23.2±4.1 in the Denosumab therapy group, significantly lower than those of the conventional treatment group [(2.8±0.9)points, (2.8±1.1)points, 26.4±3.2 and 27.3±4.0] ( P<0.01). The VAS scores at each time point after surgery in both groups decreased significantly compared with those before surgery ( P<0.05). The VAS scores continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while no significant difference was found among those at different time points in the conventional treatment group ( P>0.05). The ODI values at each time point after surgery in both groups significantly decreased compared to those before surgery ( P<0.05). The ODI values continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while in the conventional treatment group, no significant difference was found between those at 6 months after surgery and those at 3 days after surgery ( P>0.05) and they were improved at the last follow-up compared with those at 3 days after surgery ( P<0.05). The refracture rate after surgery was 6.7% (7/104) in the Denosumab therapy group, significantly lower than 16.8% (18/107) in the conventional treatment group ( P<0.05). No serious complications were observed during the antiosteoporosis period in either group. Conclusion:Compared with daily oral administration of Calcium and active Vitamin D after PKP, the conventional treatment combined with Denosumab after PKP can effectively increase the bone density, relieve pain continuously, improve functional restoration, and reduce the risk of refracture in OVCF patients.

Traditional Chinese medicines have demonstrated clinical efficacy in preventing and treating chemotherapy-induced peripheral neuropathic pain(CIPNP).However,their specific clinical application and mechanism of action require further in-depth study and exploration.There is thus a need to develop more accurate and clinically relevant animal models that reflect the occurrence and development of human diseases as a tool for research.This review provides an in-depth analysis and discussion of the recent establishment and detection criteria of existing rat and mouse animal models of paclitaxel-induced peripheral neuropathic pain.We also evaluate and explain the application of these models for the prevention and treatment of CIPNP in traditional Chinese medicine,thus providing a theoretical basis and reference for future experimental and mechanistic research on the subject.This research will benefit clinical practice and promotion,offering valuable insights into preventing and treating CIPNP using traditional Chinese medicines.

Objective:To compare the efficacy and safety of high- and standard-dose radiotherapy (HD-RT vs. SD-RT) during definitive concurrent chemoradiotherapy (dCCRT) for esophageal cancer (EC), aiming to assess the advantages and disadvantages of these two radiotherapy doses when using modern radiotherapy techniques. Methods:Literature review was conducted from PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang database, and abstracts of the American Society of Radiation Oncology (ASTRO) and the European Society of Radiotherapy and Oncology (ESTRO). Randomized controlled trials (RCT) comparing high-dose radiotherapy (HD-RT: ≥59.4 Gy,1.8 Gy per time) with standard-dose radiotherapy (SD-RT: 50 Gy, 2 Gy per time, or 50.4 Gy, 1.8 Gy per time) during dCCRT for EC were included. The retrieval time was from the establishment of the database to January 1, 2023. The meta-analysis was performed using Stata 16.0 software.Results:A total of 1 158 patients from 5 RCT that meet the inclusion criteria were finally included. In 4 RCT, subgroup analysis of 940 patients using modern radiotherapy techniques were performed. Patients in the HD-RT and SD-RT groups had similar 1-, 2-, and 3-year overall survival (OS)( RR=1.03, 95% CI=0.86-1.22, P=0.757; RR=1.05, 95% CI=0.94-1.17, P=0.433; RR=1.05, 95% CI=0.96-1.14, P=0.314; respectively) and 2- and 3-year locoregional progression-free survival (LRPFS) ( RR=0.94, 95% CI=0.82-1.08, P=0.390; RR=0.96, 95% CI=0.86-1.09, P=0.560; respectively). Patients in the HD-RT group had a higher incidence of grade ≥ 3 treatment-related adverse reactions rates ( OR=1.35, 95% CI=1.03-1.77, P=0.029) and treatment-related death rates ( OR=1.66, 95% CI=0.97-2.83, P=0.062) compared with their counterparts in the SD-RT group. In the subgroup analysis using modern radiotherapy techniques, HD-RT did not improve LRPFS compared to SD-RT, but increased the incidence of adverse reactions, and yielded no OS benefit. Conclusions:Whether modern precision radiation therapy is employed or not, SD-RT yields similar LRPFS and OS, and lower grade ≥ 3 treatment-related adverse reactions rates compared with HD-RT. Therefore, standard-dose (50 Gy, 2 Gy per time, or 50.4 Gy, 1.8 Gy per time) should be considered as the recommended dose in dCCRT for EC. Further RCT are needed to verify our conclusions.

Influenza is an acute respiratory infection caused by influenza viruses (IFV), According to the World Health Organization (WHO), seasonal IFV epidemics result in approximately 3-5 million cases of severe illness, leading to about half a million deaths worldwide, along with severe economic losses and social burdens. Unfortunately, frequent mutations in IFV lead to a certain lag in vaccine development as well as resistance to existing antiviral drugs. Therefore, it is of great importance to develop anti-IFV drugs with high efficiency against wild-type and resistant strains, needed in the fight against current and future outbreaks caused by different IFV strains. In this review, we summarize general strategies used for the discovery and development of antiviral agents targeting multiple IFV strains (including those resistant to available drugs). Structure-based drug design, mechanism-based drug design, multivalent interaction-based drug design and drug repurposing are amongst the most relevant strategies that provide a framework for the development of antiviral drugs targeting IFV.

Objective:To explore the association of miRNA-146a (miR-146a), miRNA-196a2 (miR-196a2), and miRNA-499 (miR-499) single nucleotide polymorphisms with genetic susceptibility in hepatocellular carcinoma.Methods:A case-control study was designed. A total of 175 patients (hepatocellular carcinoma group) in Affiliated Hospital of Yangzhou University from April 2015 to March 2019 and 302 healthy people undergoing physical examination during the same period (the control group) were selected. The genotype distribution of miR-146a, miR-196a2 and miR-499 in the peripheral blood of the two groups were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression model was used to analyze the association of 3 genotypes of miRNA, genotypes of hepatitis virus infectors with genetic susceptibility in hepatocellular carcinoma. The relationship between miR-146a gene polymorphism and demography factor as well as the clinical characteristics was also analyzed by using Spearman correlation analysis.Results:In hepatocellular carcinoma group, miR-146a single nucleotide polymorphism of CC, CG, GG site genotypes had 52 (29.7%) cases, 86 (49.1%) cases, 37 (21.1%) cases, respectively; in the control group, the corresponding genotypes had 137 (45.4%) cases, 135 (44.7%) cases and 30 (9.9%) cases, respectively, and the difference in genotype distribution of both groups was statistically significant ( χ2 = 17.23, P < 0.05). There were no statistical differences in genotype distribution of miR-196a2 and miR-499 ( χ2 = 0.51, P = 0.776; χ2 = 0.05, P = 0.976). Single factor logistic regression analysis showed that in the co-dominant model of miR-146a genotype, genotypes of CG ( OR = 1.96, 95% CI 1.13-3.41, P = 0.017) and GG ( OR = 3.30, 95% CI 1.85-5.89, P<0.01) had elevated risk of hepatocellular carcinoma compared with CC genotype. In the dominant model, the risk of hepatocellular carcinoma in CG+GG genotypes was increased compared with that in CC genotype ( OR=1.97, 95% CI 1.33-2.93, P = 0.001); in the recessive model, the risk of hepatocellular carcinoma in GG genotype was increased compared with that in CG+ GG genotype ( OR=2.43, 95% CI 1.44-4.11, P = 0.001). Single factor logistic regression analysis showed that there was no significant difference in the risk of hepatocellular carcinoma in the co-dominant, dominant and recessive models between miR-196a2 and miR-499 genotypes (all P > 0.05). For hepatocellular carcinoma patients with positive hepatitis B virus (HBV), CG genotype had a 2.02-fold (95% CI 1.06-5.07) risk of hepatocellular carcinoma compared with CC genotype, and GG genotype had a 3.12-fold (95% CI 1.66-10.07) risk of hepatocellular carcinoma compared with CC genotype; CG+GG genotype had a 1.91-fold (95% CI 1.85-3.38) compared with CC genotype, GG genotype had a 1.54-fold (95% CI 1.15-6.08) compared with CG+GG genotype. The increasing risk of hepatocellular carcinoma by miR-146a gene polymorphisms was not found in hepatocellular carcinoma patients with hepatitis C virus (HCV) infection or without HBV and HCV infection. Spearman correlation analysis showed that miR-146a gene polymorphisms was not related with age, gender, smoking, drinking, family history of cancer, alanine transaminase and aspartate aminotransferase (all P>0.05). Conclusions:GG and CG genotypes of miR-146a increase the risk of genetic susceptibility in hepatocellular carcinoma, especially for patients with HBV infection. miR-196a2 and miR-499 single nucleotide polymorphisms don't increase the risk of hepatocellular carcinoma.

The scalpel is the most practical tool for surgeons. The traditional scalpel is a blade with a split handle, but the length of the blade cannot be adjusted, and it is easy to scratch medical staff. In order to solve the above problems, a retractable scalpel handle was designed by the medical staffs of department of general surgery, Affiliated Hospital of Yangzhou University (Clinical Teaching Hospital of Dalian Medical University), and obtained the National Utility Model Patent of China (ZL 2019 2 0203154.9). The telescopic scalpel adopted the design of rotary telescopic sleeve and threaded column handle to achieve the purpose of built-in blade. By rotating the handle at one end of the handle, the length of the surgical blade extending out of the sleeve could be adjusted according to the actual needs. The structure of the device is simple and easy to operate. The adjustable blade length could also achieve the purpose of accurate operation while effectively avoiding the injury of medical personnel during the operation.

Objective To evaluate hepatectomy by anterior approach combined with liver hanging maneuver against conventional right hepatectomy in patients with large hepatocellular carcinoma (HCC).Methods Of the 62 cases,29 patients underwent anterior approach hepatectomy and 33 did conventional hepatectomy.Results The overall operative time (t =1.815,P =0.037) and parenchymal transsection time (t =4.591,P=0.000) were longer in the anterior approach group than in the conventional group.More cases got radical resection in the anterior group (x2 =7.280,P =0.007).Log-rank test showed that 1,3 and 5-year overall survival rate (OS) in the anterior approach group and the conventional group was 86.1％,50.1％,32.6％ vs 75.8％,30.3％,18.9％,respectively (x2 =5.24,P=0.022),1,3 and 5-year disease free survival rate (DFS) were 75.3％,42.1％,31.0％ vs 66.1％,24.4％,10.1％,respectively (x2 =4.38,P =0.037),and recurrence rate were 23.6％,49.5％,64.8％ vs 36.7％,63.7％,82.5％,respectively (x2 =5.61,P =0.018).Conclusion Long term survival of patients with large sized HCC undergoing hepatectomy through the anterior approach combined with liver hanging maneuver is better than that of conventional approach.

Objective: To evaluate hepatectomy by anterior approach combined with liver hanging maneuver against conventional right hepatectomy in patients with large hepatocellular carcinoma (HCC). Methods: Of the 62 cases, 29 patients underwent anterior approach hepatectomy and 33 did conventional hepatectomy. Results: The overall operative time (t=1.815, P=0.037) and parenchymal transsection time (t=4.591, P=0.000) were longer in the anterior approach group than in the conventional group. More cases got radical resection in the anterior group (χ²=7.280, P=0.007). Log-rank test showed that 1, 3 and 5-year overall survival rate (OS) in the anterior approach group and the conventional group was 86.1%, 50.1%, 32.6% vs 75.8%, 30.3%, 18.9%, respectively (χ²=5.24, P=0.022), 1, 3 and 5-year disease free survival rate (DFS) were 75.3%, 42.1%, 31.0% vs 66.1%, 24.4%, 10.1%, respectively (χ²=4.38, P=0.037), and recurrence rate were 23.6%, 49.5%, 64.8% vs 36.7%, 63.7%, 82.5%, respectively (χ²=5.61, P=0.018). Conclusion Long term survival of patients with large sized HCC undergoing hepatectomy through the anterior approach combined with liver hanging maneuver is better than that of conventional approach.

OBJECTIVETo observe the expression change of mitophagy-related proteins in skeletal muscle in rats with spleen deficiency syndrome and to explain the partial action mechanism of acupuncture at Zusanli (ST 36) for spleen deficiency syndrome.

METHODSForty male SD rats, after normal feeding, were randomly divided into a normal group, a spleen deficiency group, a Zusanli group and a non-acupoint group, ten rats in each group. Except the normal group, the three factors modeling method was used for 14 days to establish the model of spleen deficiency syndrome on the other 3 groups. The rats in the Zusanli group were treated with EA at bilateral "Zusanli" (ST 36), while the rats in the non-acupoint group were treated with EA at bilateral non acupoint (dense-sparse wave, frequency of 2 Hz/100 Hz, 20 min per treatment, once a day for 10 days). The rats in the normal group and spleen deficiency group were treated with immobilization for 20 min per day, and no EA was given. The HPLC method was applied to measure the content of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) in skeletal muscle. The Western blotting method was applied to measure the expression of adenosine monophosphate activated protein kinase (AMPK), p-AMPK, ULK1, p-ULK1，LC3-Ⅰand LC3-Ⅱ in skeletal muscle.

RESULTSThe ATP content in the spleen deficiency group was significantly lower than that in the normal group (<0.01); the ATP content in the Zusanli group was significantly higher than that in the spleen deficiency group (<0.05) but lower than that in the normal group (<0.05), there was no significant difference between the non-acupoint group and the spleen deficiency group (>0.05). Compared with the normal group, the AMP/ATP in the spleen deficiency group and the Zusanli group were significantly up-regulated (<0.01, <0.05). The differences of p-AMPK/AMPK between the spleen deficiency group and the normal group was not significant (>0.05). Compared with the normal group and spleen deficiency group, the p-AMPK/AMPK in the Zusanli group was significantly up-regulated (both <0.05). The p-ULK1/ULK1 and LC3-Ⅱ/LC3-Ⅰin the Zusanli group was higher than those in the normal group and spleen deficiency group (all <0.01).

CONCLUSIONEA at "Zusanli" (ST 36) might activate AMPK and produce stable ULK1/AMPK compound and increase the mitochondrial autophagy, which could regulate spleen-stomach and treat spleen deficiency.