Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

Objective:To investigate the foot development of children and adolescents in Guangzhou and provide reference for clinical diagnosis and treatment of pediatric flat feet.Methods:Cross-sectional study.The foot health screening data of students from 3 kindergartens, 1 primary school, and 1 middle school in Guangzhou between January 2023 and June 2023 were collected.Foot parameters including foot length, arch index (AI), arch volume (AV), hallux valgus angle, forefoot width, and heel width were measured.Additionally, general information such as gender, age, height, weight, and body mass index (BMI) was also recorded.The students were divided into groups by gender, left and right sides, and subgroups by age (in years).The changes of foot parameters with age were observed in each group, and percentile line charts were drawn.Furthermore, the correlation among BMI, AI, AV, hallux valgus angle and foot length were analyzed.Results:A total of 2 520 students aged 3-18 years were included according to the inclusion criteria.There were 1 382 males and 1 138 females, with a total of 5 040 feet on both sides.The AI of boys decreased at a constant rate before the ages of 14 years.However, the AI values between the ages of 14 and 18 years showed no statistical difference ( P=0.743), with the mean value of 0.27 (0.25, 0.30).The AI of girls decreased at a constant rate before the ages of 12 years.The AI values between the ages of 12 and 18 years had no statistical difference ( P=0.155), with the mean value of 0.25 (0.23, 0.28).In every age group from 3 to 18 years old, the AI value of girls was smaller by 0.01-0.04 than that of boys (all P<0.05).At the ages of 3, 4, 5, 6, 11, and 17 years, the AI of the right foot was 0.01 smaller than that of the left foot (all P<0.05).There were statistically significant differences in arch type between boys and girls at ages other than 3 and 8 years old (all P<0.05).In some age groups, BMI is positively correlated with AI and AV, foot length is positively correlated with AI, and hallux valgus angle is correlated with AI positively and AV negatively.There was a negative correlation between AI and AV across all age groups. Conclusions:Chinese children and adolescents, represented by Guangzhou, have slower development in foot and a larger AI.The arch is in the development stage before the age of 14 years in boys and 12 years in girls.A proper physical therapy is recommended if the AI value deviates from the normal range during development.

Objective:To investigate the foot development of children and adolescents in Guangzhou and provide reference for clinical diagnosis and treatment of pediatric flat feet.Methods:Cross-sectional study.The foot health screening data of students from 3 kindergartens, 1 primary school, and 1 middle school in Guangzhou between January 2023 and June 2023 were collected.Foot parameters including foot length, arch index (AI), arch volume (AV), hallux valgus angle, forefoot width, and heel width were measured.Additionally, general information such as gender, age, height, weight, and body mass index (BMI) was also recorded.The students were divided into groups by gender, left and right sides, and subgroups by age (in years).The changes of foot parameters with age were observed in each group, and percentile line charts were drawn.Furthermore, the correlation among BMI, AI, AV, hallux valgus angle and foot length were analyzed.Results:A total of 2 520 students aged 3-18 years were included according to the inclusion criteria.There were 1 382 males and 1 138 females, with a total of 5 040 feet on both sides.The AI of boys decreased at a constant rate before the ages of 14 years.However, the AI values between the ages of 14 and 18 years showed no statistical difference ( P=0.743), with the mean value of 0.27 (0.25, 0.30).The AI of girls decreased at a constant rate before the ages of 12 years.The AI values between the ages of 12 and 18 years had no statistical difference ( P=0.155), with the mean value of 0.25 (0.23, 0.28).In every age group from 3 to 18 years old, the AI value of girls was smaller by 0.01-0.04 than that of boys (all P<0.05).At the ages of 3, 4, 5, 6, 11, and 17 years, the AI of the right foot was 0.01 smaller than that of the left foot (all P<0.05).There were statistically significant differences in arch type between boys and girls at ages other than 3 and 8 years old (all P<0.05).In some age groups, BMI is positively correlated with AI and AV, foot length is positively correlated with AI, and hallux valgus angle is correlated with AI positively and AV negatively.There was a negative correlation between AI and AV across all age groups. Conclusions:Chinese children and adolescents, represented by Guangzhou, have slower development in foot and a larger AI.The arch is in the development stage before the age of 14 years in boys and 12 years in girls.A proper physical therapy is recommended if the AI value deviates from the normal range during development.

Objective:To explore the effects of G protein-coupled receptor 55 (GPR55) antagonist CID16020046 on renal fibrosis in mice, and provide a new method and idea for the treatment of renal fibrosis.Methods:(1) GPR55 overexpression and GPR55 antagonist CID16020046 were used in renal fibroblasts (NRK-49F) of rats, respectively. Meanwhile,transforming growth factor-β1 (TGF-β1) was applied in the NRK-49F cells to observe the expression of fibrosis-related factors and inflammatory factors. (2) A mouse model of renal fibrosis with unilateral ureteral obstruction (UUO) was established in vivo. Eight-week-old male C57BL/6J mice (20-25 g) were randomly divided into three groups according to the random number table method: sham group ( n=6), model group (UUO group, n=7), model + CID16020046 drug (UUO+CID group, n=8). The drug CID16020046 (10 mg/kg) was intraperitoneally injected 1 day before modeling, on the day of modeling and every day after surgery in UUO+CID group, and the corresponding dose of 0.9% normal saline was injected intraperitoneally in sham and UUO groups.The mice were sacrificed for sampling 7 days after UUO surgery, and their renal function indicators, liver transaminase, and cardiac markers were examined. Western blotting and quantitative real-time PCR were used to detect the expression of renal fibrosis-related factors and inflammatory factors. Immunohistochemistry staining, Sirius red staining and Masson trichrome staining were used to detect the pathological changes of renal tissues. Results:(1) After NRK-49F cells were stimulated by TGF-β1, the mRNA and protein expression levels of GPR55 were significantly increased (both P<0.05). There was no statistically significant difference in the mRNA expression of fibrosis-related factors fibronectin and collagen Ⅰ, and inflammatory factors interleukin-1β and tumor necrosis factor-α between TGF-β1 group and TGF-β1 + GPR55 overexpression group (all P>0.05). Compared with the TGF-β1 group, the protein expression levels of fibrosis-related factors alpha-smooth muscle actin (α-SMA) and vimentin, and the mRNA expression levels of collagen Ⅰ and α-SMA were lower in the TGF-β1 + CID group (all P<0.05). (2) Compared with sham group, the mRNA and protein expression levels of GPR55 in UUO group were higher (both P<0.05). The serum creatinine in the UUO+CID group was lower compared to the UUO group ( P<0.05). There was no statistically significant difference in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine kinase isoenzyme between UUO group and UUO+CID group (all P>0.05). Compared with the UUO group, the protein expression levels of renal fibrosis-related factors fibronectin, collagen Ⅰ and vimentin, and the mRNA expression levels of fibronectin, collagen Ⅰ, collagen Ⅲ and α-SMA were lower in the UUO+CID group (all P<0.05). The degree of renal tubular dilation and interstitial collagen fiber deposition in the UUO+CID group was significantly reduced compared to the UUO group (all P<0.05). Conclusions:CID16020046 can reduce serum creatinine in UUO mice, protect renal function, and simultaneously decrease the expression of fibrosis-related factors in renal fibroblasts and mouse kidney tissues, thereby alleviating renal fibrosis.

Objective To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. Methods In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX;10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. Results In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). Conclusion A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Objective To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. Methods In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX;10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. Results In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). Conclusion A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Objective: To investigate the awareness and identify the influencing factors of sexual knowledge among primary and middle school students in Butuo County, Sichuan Province, so as to provide insights into sex education. Methods: Six primary and middle schools were randomly sampled from 40 primary and middle schools in Butuo County using the cluster sampling method on March and April, 2021, and a class was randomly sampled from each of grades 4 to 6 of primary schools and grades 1 to 3 of junior high schools, with all students from the class as study subjects. Students' demographic features and awareness of sexual knowledge were investigated using self-designed questionnaires, and the factors affecting the awareness of sexual knowledge were identified among primary and middle school students using multivariable linear regression analysis. Results: A total of 980 questionnaires were allocated, and 957 valid questionnaires were recovered, with an effective recovery rate of 97.65%. The respondents included 458 boys ( 47.86% ) and 499 girls ( 52.14% ), and included 908 students with Yi Ethnicity. The respondents included 802 primary school students ( 83.80% ) and 155 junior high school students ( 16.20% ). The awareness of sexual knowledge was 21.94% among the primary and middle school students, and their sexual knowledge was predominantly derived from parents ( 338 students, 35.32% ) and teachers ( 335 students, 35.01% ). The awareness of sexual knowledge was significantly lower in boys than in girls ( 17.69% vs. 25.86%; χ2=8.344, P=0.004 ), and the awareness of sexual knowledge appeared a tendency towards a rise with age ( χ2trend = 63.908, P<0.001 ). Low awareness of sexual knowledge was seen in students with fathers going out for labor ( 19.54% ), mothers going out for labor (11.24%) and living in the countryside ( 14.32% ) ( χ2=7.790, 9.224 and 34.144, all P<0.01 ). Multivariable linear regression analysis showed that students living in the countryside, students’ mothers going out for labor, ages of 12 to 14 years and ages of over 14 years were factors affecting the score of sexual knowledge ( β'=-0.072, 0.341, 0.645 and 0.843, all P<0.05 ). Conclusions The awareness of sexual knowledge is low among primary and middle school students in Butuo County. Health education of sexual knowledge should be emphasized on male students, those living in the countryside and students with mothers going out for labor.

A 66-year-old male urothelial carcinoma patient with liver and lymph node metastasis received an IV infusion of paclitaxel for injection (albumin bound) 400 mg on day 1 and tegafur, gimeracil and oteracil potassium capsules 50 mg orally twice daily on day 1 to day 14, the interval was 1 week, and each cycle was 21 days. A total of 9 cycles of chemotherapy were performed. The patient complained of priapism occurring about 15 hours (about 1: 00 of the next morning) after intravenous infusion of paclitaxel (albumin bound) in the cycles 1-5 and 7-9, which could disappear about 2 hours later. No special treatment was given. After that, paclitaxel for injection (albumin bound) was not used, and the patient did not have the above symptoms again after changing to immunotherapy as disease progresses. It was considered that the patient′s priapism might be related to paclitaxel for injection (albumin bound).

A 66-year-old male urothelial carcinoma patient with liver and lymph node metastasis received an IV infusion of paclitaxel for injection (albumin bound) 400 mg on day 1 and tegafur, gimeracil and oteracil potassium capsules 50 mg orally twice daily on day 1 to day 14, the interval was 1 week, and each cycle was 21 days. A total of 9 cycles of chemotherapy were performed. The patient complained of priapism occurring about 15 hours (about 1: 00 of the next morning) after intravenous infusion of paclitaxel (albumin bound) in the cycles 1-5 and 7-9, which could disappear about 2 hours later. No special treatment was given. After that, paclitaxel for injection (albumin bound) was not used, and the patient did not have the above symptoms again after changing to immunotherapy as disease progresses. It was considered that the patient′s priapism might be related to paclitaxel for injection (albumin bound).

Objective To evaluate the left atrial(LA) function in patients with severe preeclampsia ( SPE) by full-volume imaging technology. Methods Forty-two patients of SPE were randomly chosen as SPE group,34 healthy pregnant women were selected as the control group. LA related function parameters including LA maximum volume( LAVmax),LA minimum volume( LAVmin),LA pre-atrium contraction volume(LAVpre),LA reservoir volume(LARV),LA passive emptying volume(LAPEV),LA contraction volume(LACV),LA expansion index(LAEI),LA passive emptying fraction(LAPEF),LA passive emptying fraction( LAAEF ) were separately required by biplane area-length method and full-volume imaging technology in antepartum and postpartum. Results Compared with control group before delivery,the parameters of SPE group before delivery such as LAVmax,LAVmin,LAVpre were higher,LAEI,LAPEF, LAAEF indexed to body surface area(BSA) were lower(all P ＜0.01).Compared with control group before delivery,the parameters of control group after delivery such as LAVmax,LAVmin,LAVpre were lower( all P ＜0.05),LAEI, LAAEF calculated as ratio to BSA were somewhat reduced,LAPEF calculated as ratio to BSA was relatively higher(all P ＞0.05).Compared with SPE group before delivery,the parameters of SPE group after delivery such as LAVmax,LAVmin,LAVpre were lower,LAEI,LAPEF,LAAEF indexed to BSA were higher( all P ＜0.01). Compared with control group after delivery,the parameters of SPE group after delivery such as LAVmax,LAVmin,LAVpre were still incresed ( all P ＜ 0.05 ), LAEI,LAPEF, LAAEF indexed to BSA were relatively lower( all P ＞0.05). Conclusions Full-volume imaging technology can quantitatively evaluate the LA function. LA reservoir function,conduit function and booster pump function are reduced in SPE before delivery,LA rereservoir function,conduit function and booster pump function are basically recovery in SPE after delivery.