Objective:To evaluate the radiological and functional outcomes of moderate to severe hallux valgus patients with enlarged distal metatarsal articular angle (DMAA) underwent modified Chevron osteotomy.Methods:The clinical data of patients with moderate and severe hallux valgus with increased distal metatarsal joint angle who accepted surgery operation in the Department of Foot and Ankle Surgery of Yantaishan Hospital from October 2020 to December 2022 were retrospectively analyzed. All patients underwent modified Chevron osteotomy. Taking the proximal end of the metatarsal head centre as the osteotomy apex, the vertical arm osteotomy line in the sagittal plane made an angle of ≤80° with the metatarsal stem, the horizontal plane was inclined to the lateral distal end of the metatarsal head by about 10°, and the sagittal plane metatarsal arm osteotomy line made an angle of ≥90° with the vertical arm osteotomy line; at the proximal osteotomy surface, another cuneiform bone with its base on the medial and its apex on the lateral was resected. The deformity correction was insufficient and Akin osteotomy was performed in combination. Weil osteotomy was performed in combination with metatarsalgia. Radiological assessment including the hallux valgus angle (HVA), intermetatarsal angle (IMA), DMAA, the joint congruity angle (JCA), forefoot bone width and soft tissue width was performed preoperatively and at last follow-up postoperatively. American Orthopedic Foot and Ankle Society/hallux metatarsophalangeal-interphalangeal scale (AOFAS/HMIS) was used for clinical and functional evaluation, total score from 0 to 100, with higher scores indicating better function.Visual analogue scale (VAS) was used for pain valuation, total score from 0 to 10, with higher scores indicating more pain. A questionnaire survey on patient satisfaction was conducted at the last follow-up. Shapiro-Wilk test was used for normal distribution test, and measurement data following normal distribution were represented as Mean±SD. Paired t-test was used for comparison before and after operation. Other indicators conformed to non-normal distribution were denoted by M( Q1, Q3) and were tested by Wilcoxon signed-rank test. P<0.05 was considered statistically significant. Results:Fifty-two feet of 48 patients (5 males, 43 females; mean age (52.4±14.9) years; range, 24 to 78 years) were enrolled. Before the operation, 8 feet combined with metatarsalgia, among them, 7 feet underwent modified Chevron+ Akin+ Weil osteotomy, and 1 foot underwent modified Chevron+ Weil osteotomy. Among the 44 feet without metatarsalgia, 11 feet underwent modified Chevron osteotomy and 33 feet underwent modified Chevron+ Akin osteotomy. The mean follow-up time was 17.8 months (12-24 months). The HVA angle decreased from 38.30°±7.59° before surgery to 10.00°±5.73° at the last follow-up; the IMA angle decreased from 16.08°(12.89°, 18.24°) to 4.81°(3.62°, 7.57°); the DMAA angle decreased from 18.35°(13.03°, 27.47°) to 4.52°(2.68°, 7.09°); JCA decreased significantly from 15.93°(10.25°, 23.06°) to 3.56°(1.71°, 6.98°); forefoot bone width decreased from (90.05±6.12) mm to (82.75±5.01) mm; forefoot soft tissue width decrease from 102.25(96.77, 107.15) mm to 98.08(91.01, 100.60) mm; the VAS decreased from 6(5.5, 7) points to 0(0, 0) points; the score according to the AOFAS/HMIS forefoot was increased from 49(42, 52.5) points to 90(83.5, 95) points; which were statistically significant compared with that before the operation (all P<0.01). There was no statistically significant difference in the first metatarsal length before the operation and at the last follow-up [54.60(52.86, 56.42) mm vs. 54.29(51.85, 56.35) mm, P>0.05]. In the post-operative period, there were 8 feet had limited metatarsophalangeal joint movement, 3 feet had limited interphalangeal joint movement, 5 feet had limited movement in both joints, which did not affect walking and function; 3 feet of partial recurrence of hallux valgus, 2 feet of screw irritation pain, 1 foot of cystic degeneration of the first metatarsal head, and no complications such as metastatic metatarsalgia. The satisfaction survey showed that the satisfaction rate of patients with the orthopedic effect was 90.4% (47/52). Conclusion:The modified Chevron osteotomy is effective in the treatment of moderate to severe hallux valgus with enlarged DMAA. Careful intraoperative operation and standardized postoperative rehabilitation training can reduce complications.

Objective:To investigate role of miR-4738-3p in targeting tryptophan 2,3-dioxygenase 2(TDO2)to regulate energy metabolism and inhibit immune escape in thyroid cancer cells.Methods:A total of 68 cases of thyroid cancer tissues and their corresponding adjacent non-cancerous tissues were collected,expressions of miR-4738-3p and TDO2 in tissues and cell lines were de-tected by qRT-PCR,relationship between miR-4738-3p expression and clinicopathological characteristics was analyzed.Effects of miR-4738-3p and TDO2 on proliferation,migration,invasion,energy metabolism and immune escape of TPC-1 and BCPAP cells were examined through CCK-8,clone formation,wound healing,Transwell experiments,biochemical analyses,ELISA and NK cell co-culture experiments,targeting relationship between miR-4738-3p and TDO2 was validated by dual luciferase reporter gene assay.In vivo xenograft experiments and immunohistochemical detections were conducted to observe effects of miR-4738-3p on tumorigenesis and expression of immune escape-related proteins in TPC-1 and BCPAP cells.Results:miR-4738-3p was lowly expressed(P<0.05),while TDO2 was highly expressed in thyroid cancer(P<0.05).Tumor size,lymph node metastasis and TNM staging were correlated with expression of miR-4738-3p(P<0.05).Compared with miR-NC group,miR-4738-3p mimics group exhibited decreased prolifera-tion,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions,tumor volume,mass,Ki-67,TDO2 and PD-L1 expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).miR-4738-3p inhibitor group showed increased proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Binding sites were identified between miR-4738-3p and TDO2,and their expression were negatively correlated(r=-0.485 3,P<0.001).Compared with sh-NC group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were decreased in sh-TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).Compared with Scrambled group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were increased in TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Conclusion:miR-4738-3p targets TDO2 to regulate energy metabolism,inhibiting thyroid cancer cell proliferation,metastasis and immune escape.

Objective:To investigate role of miR-4738-3p in targeting tryptophan 2,3-dioxygenase 2(TDO2)to regulate energy metabolism and inhibit immune escape in thyroid cancer cells.Methods:A total of 68 cases of thyroid cancer tissues and their corresponding adjacent non-cancerous tissues were collected,expressions of miR-4738-3p and TDO2 in tissues and cell lines were de-tected by qRT-PCR,relationship between miR-4738-3p expression and clinicopathological characteristics was analyzed.Effects of miR-4738-3p and TDO2 on proliferation,migration,invasion,energy metabolism and immune escape of TPC-1 and BCPAP cells were examined through CCK-8,clone formation,wound healing,Transwell experiments,biochemical analyses,ELISA and NK cell co-culture experiments,targeting relationship between miR-4738-3p and TDO2 was validated by dual luciferase reporter gene assay.In vivo xenograft experiments and immunohistochemical detections were conducted to observe effects of miR-4738-3p on tumorigenesis and expression of immune escape-related proteins in TPC-1 and BCPAP cells.Results:miR-4738-3p was lowly expressed(P<0.05),while TDO2 was highly expressed in thyroid cancer(P<0.05).Tumor size,lymph node metastasis and TNM staging were correlated with expression of miR-4738-3p(P<0.05).Compared with miR-NC group,miR-4738-3p mimics group exhibited decreased prolifera-tion,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions,tumor volume,mass,Ki-67,TDO2 and PD-L1 expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).miR-4738-3p inhibitor group showed increased proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Binding sites were identified between miR-4738-3p and TDO2,and their expression were negatively correlated(r=-0.485 3,P<0.001).Compared with sh-NC group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were decreased in sh-TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).Compared with Scrambled group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were increased in TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Conclusion:miR-4738-3p targets TDO2 to regulate energy metabolism,inhibiting thyroid cancer cell proliferation,metastasis and immune escape.

Objective:To evaluate the radiological and functional outcomes of moderate to severe hallux valgus patients with enlarged distal metatarsal articular angle (DMAA) underwent modified Chevron osteotomy.Methods:The clinical data of patients with moderate and severe hallux valgus with increased distal metatarsal joint angle who accepted surgery operation in the Department of Foot and Ankle Surgery of Yantaishan Hospital from October 2020 to December 2022 were retrospectively analyzed. All patients underwent modified Chevron osteotomy. Taking the proximal end of the metatarsal head centre as the osteotomy apex, the vertical arm osteotomy line in the sagittal plane made an angle of ≤80° with the metatarsal stem, the horizontal plane was inclined to the lateral distal end of the metatarsal head by about 10°, and the sagittal plane metatarsal arm osteotomy line made an angle of ≥90° with the vertical arm osteotomy line; at the proximal osteotomy surface, another cuneiform bone with its base on the medial and its apex on the lateral was resected. The deformity correction was insufficient and Akin osteotomy was performed in combination. Weil osteotomy was performed in combination with metatarsalgia. Radiological assessment including the hallux valgus angle (HVA), intermetatarsal angle (IMA), DMAA, the joint congruity angle (JCA), forefoot bone width and soft tissue width was performed preoperatively and at last follow-up postoperatively. American Orthopedic Foot and Ankle Society/hallux metatarsophalangeal-interphalangeal scale (AOFAS/HMIS) was used for clinical and functional evaluation, total score from 0 to 100, with higher scores indicating better function.Visual analogue scale (VAS) was used for pain valuation, total score from 0 to 10, with higher scores indicating more pain. A questionnaire survey on patient satisfaction was conducted at the last follow-up. Shapiro-Wilk test was used for normal distribution test, and measurement data following normal distribution were represented as Mean±SD. Paired t-test was used for comparison before and after operation. Other indicators conformed to non-normal distribution were denoted by M( Q1, Q3) and were tested by Wilcoxon signed-rank test. P<0.05 was considered statistically significant. Results:Fifty-two feet of 48 patients (5 males, 43 females; mean age (52.4±14.9) years; range, 24 to 78 years) were enrolled. Before the operation, 8 feet combined with metatarsalgia, among them, 7 feet underwent modified Chevron+ Akin+ Weil osteotomy, and 1 foot underwent modified Chevron+ Weil osteotomy. Among the 44 feet without metatarsalgia, 11 feet underwent modified Chevron osteotomy and 33 feet underwent modified Chevron+ Akin osteotomy. The mean follow-up time was 17.8 months (12-24 months). The HVA angle decreased from 38.30°±7.59° before surgery to 10.00°±5.73° at the last follow-up; the IMA angle decreased from 16.08°(12.89°, 18.24°) to 4.81°(3.62°, 7.57°); the DMAA angle decreased from 18.35°(13.03°, 27.47°) to 4.52°(2.68°, 7.09°); JCA decreased significantly from 15.93°(10.25°, 23.06°) to 3.56°(1.71°, 6.98°); forefoot bone width decreased from (90.05±6.12) mm to (82.75±5.01) mm; forefoot soft tissue width decrease from 102.25(96.77, 107.15) mm to 98.08(91.01, 100.60) mm; the VAS decreased from 6(5.5, 7) points to 0(0, 0) points; the score according to the AOFAS/HMIS forefoot was increased from 49(42, 52.5) points to 90(83.5, 95) points; which were statistically significant compared with that before the operation (all P<0.01). There was no statistically significant difference in the first metatarsal length before the operation and at the last follow-up [54.60(52.86, 56.42) mm vs. 54.29(51.85, 56.35) mm, P>0.05]. In the post-operative period, there were 8 feet had limited metatarsophalangeal joint movement, 3 feet had limited interphalangeal joint movement, 5 feet had limited movement in both joints, which did not affect walking and function; 3 feet of partial recurrence of hallux valgus, 2 feet of screw irritation pain, 1 foot of cystic degeneration of the first metatarsal head, and no complications such as metastatic metatarsalgia. The satisfaction survey showed that the satisfaction rate of patients with the orthopedic effect was 90.4% (47/52). Conclusion:The modified Chevron osteotomy is effective in the treatment of moderate to severe hallux valgus with enlarged DMAA. Careful intraoperative operation and standardized postoperative rehabilitation training can reduce complications.

Exosomes are nano-sized phospholipid bilayer vesicles containing abundant and complex biomolecules, such as DNA, mRNAs, microRNAs (miRNAs), lipids, and proteins. Exosomes can be secreted and ingested by most types of cells to transfer information through intercellular transport. After uptake by recipient cells, exosomes release bioactive substances to regulate the biological processes of recipient cells, such as promoting tumor growth and metastasis. Changes of exosomes and their contents are associated with a variety of diseases. In recent years, the role of exosomal miRNAs in the development and progression of hepatocellular carcinoma (HCC) caused by viral hepatitis has attracted wide attention, and exosomal miRNAs from different sources play different roles in this process. This article briefly reviews the research on the role of exosomal miRNAs in the development and progression of viral hepatitis-related HCC and proposes that exosomal miRNAs may be the targets for immunotherapy for HCC microenvironment.

Objective:This study was conducted to investigate the levels of IL-23 and IL-17 in sera and tumor tissues and to ana-lyze their association with clinico-pathological parameters in patients with colorectal cancer (CRC). Methods:A total of 24 healthy sub-jects and 56 patients with CRC were recruited in this study. Enzyme-linked immunosorbent assay was performed to measure the concen-trations of IL-23 and IL-17 in the sera of CRC patients and healthy controls and in cultured normal tissues and tumor tissues from CRC patients. Results:The levels of serum IL-23 and IL-17 were significantly higher in CRC patients than in healthy controls (P<0.01). The supernatant levels of IL-23 and IL-17 in tumor tissues were significantly higher than in normal tissues (P<0.05). Serum IL-17 level was correlated with tumor location, lymph node metastasis, and TNM stage (P<0.05), whereas serum IL-23 level showed no correlation with all clinico-pathological parameters (P>0.05). Tumor supernatant IL-17 level was correlated with tumor differentiation, lymph node metastasis, and TNM stage (P<0.05), whereas tumor supernatant IL-23 level was correlated only with TNM stage (P<0.05). Conclu-sion:IL-23 and IL-17 may be involved in the immuno-pathogenesis of CRC progression.

Objective:To explore the changes and possible mechanisms of circulating Tc 17 cells in patients with colorectal cancer ( CRC) following disease progression .Methods:The peripheral blood were collected from 54 patients with colorectal cancer . the proportions of Tc17 cells in peripheral blood mononuclear cells (PBMCs) and cultured PBMCs treated by IL-1β, IL-6 and TGF-βin different concentrations were determined by flow cytometry;the levels of IL-1β, IL-17A, IL-23 and IL-6 in sera were measured by ELISA.Results:The proportions of Tc17 cells and the levels of IL-1β, IL-17A, IL-23 and IL-6 were significantly higher than those in healthy controls (P<0.05).Compared with early CRC, the proportions of Tc17 cells and the levels of IL-1β, IL-17A in advanced CRC were significantly decreased, but the level of IL-6 was significantly increased (P<0.05).The difference of IL-23 level between early and late groups was not significant (P>0.05).In vitro experiments confirmed that IL-1βor high concentrations of IL-6 and TGF-βcould significantly increase the number of Tc 17 cells in PBMCs.Conclusion: The changes of circulating Tc 17 cells in the progression of colorectal cancer are possibly modulated by IL-1β, IL-23, IL-6 and TGF-β.

Objective To compare ratio of circulating Th17 over Tc17 cells in patients with colorectal polyp (CRP), colorectal adenoma (CRA) and colorectal cancer (CRC),and analyse their relationship. Methods The ratio of circulating Th17 over Tc17 cells in 93 patients(17 CRP, 34 CRA and 42 CRC)and 17 healthy donors were examined by flow cytometry;Serum levels of IL-17A and IL-23 were tested by ELISA. Results The ratio of circulating Th17 over Tc17 cells and the se-rum levels of IL-17A and IL-23 were the lowest in healthy control groups, medium in CRP and CRA groups and the highest in CRC groups (P＜0.05). The proportions of Tc17 cells in CRA groups were significantly higher compared to those in CRP groups,but no statistical significance of proportion of circulating Th17 cells as well as serum levels of IL-17A and IL-23 be-tween CRA and CRP groups was observed (P>0.05). Further analysis showed that there was a positive correlation between proportions of circulating Th17 and Tc17 cells (rs=0.594, P＜0.001). Conclusion The proportions of circulating Th17 and Tc17 cells were positively related and the ratio of Th17 over Tc17 was markedly increased from CRP group or CRA group to CRC group.