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Abstract Background Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression. Methods Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as a potential oncogenic factor. We investigated the relationship between FGF7 expression and various clinical parameters. A series of in vitro experiments were undertaken to evaluate the effect of CAFs-derived FGF7 on OC cell activities, such as proliferation, migration, and invasion. Single-cell transcriptomic analysis was also conducted to elucidate the interaction between FGF7 and its receptor. Detailed mechanistic investigations sought to clarify the pathways through which FGF7 fosters OC progression. Results Our findings indicate that higher FGF7 levels correlate with advanced tumor stages, increased vascular invasion, and poorer prognosis. CAFs-derived FGF7 significantly enhanced OC cell proliferation, migration, and invasion. Single-cell analysis and in vitro studies revealed that CAFs-derived FGF7 inhibits the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF-1α) via FGFR2 interaction. Activation of the FGF7/HIF-1α pathway resulted in the upregulation of mesenchymal markers and downregulation of epithelial markers. Importantly, in vivo treatment with neutralizing antibodies targeting CAFs-derived FGF7 substantially reduced tumor growth. Conclusion Neutralizing FGF7 in the medium or inhibiting HIF-1α signaling reversed the effects of FGF7-mediated EMT, emphasizing the dependence of FGF7-mediated EMT on HIF-1α activation. These findings suggest that targeting the FGF7/HIF-1α/EMT axis may offer new therapeutic opportunities to intervene in OC progression.

AIM: To investigate the effect of orbital decompression on the central macular choroidal thickness(CMCT)in patients with thyroid-associated ophthalmopathy(TAO).METHOD: Prospective clinical studies. A total of 29 TAO patients(42 eyes)treated in our department from January 2021 to January 2022 were analyzed, and they were divided into 20 cases(30 eyes)in the moderate and severe group and 9 cases(12 eyes)in the extremely severe group. Both groups of patients received orbital decompression, and the changes of CMCT, visual acuity, intraocular pressure, exophthalmos, and clinical activity score(CAS)at 3 and 6mo before and after surgery were compared between the two groups.RESULTS: All patients completed follow-up. The CMCT, exophthalmos, intraocular pressure, and CAS of the extremely severe group at 3 and 6mo were 355.13±15.59 and 339.61±13.17μm, 19.33±2.23 and 17.83±1.70mm, 18.86±3.05 and 18.09±1.37mmHg, 3.75±0.87 and 2.42±1.00 points, respectively. The moderate and severe group was 325.00±10.48 and 321.04±11.34μm, 16.07±1.74 and 15.6±1.98mm, 16.65±2.04 and 16.03±2.3mmHg, 1.50±0.51 and 1.43±0.50 points, and there was differences with those before operation(extremely severe group: 396.46±17.61μm, 22.00±2.3mm, 21.85±2.82mmHg, 5.33±1.44 points; moderate and severe group: 335.77±11.60μm, 19.07±1.84mm, 18.89±3.06mmHg, 1.63±0.49 points; all P

Abstract Background There has been no ideal treatment for freezing-phase frozen shoulder to rapidly relieve pain and improve joint mobility. No any other team directly compared the effectiveness of combination of arthroscopic release and corticosteroid hydrodilatation with corticosteroid hydrodilatation only in treatment of freezing-phase frozen shoulder. Methods Seventy-two patients with freezing-phase frozen shoulder were randomly assigned to combined arthroscopic release with corticosteroid hydrodilatation (group A) or corticosteroid hydrodilatation only (group B). Clinical states were examined at baseline and periodically (Weeks 1, 4, 12, 24 and 1 year) after intervention by passive ROM; visual analog scale (VAS); UCLA and Disabilities of the Arm, Shoulder, and Hand (DASH) score. Results The passive ROM, VAS, UCLA and DASH scores always improved along the time points (all p 0.01), the differences between group A and group B were all lower than minimal clinically important difference (MCID). At Week 12, the UCLA sores and DASH scores were 26.8 ± 3.8, 14.2 ± 2.0 in group A versus 22.3 ± 3.4, 22.5 ± 3.1 in group B (all p

Abstract Photomediated immunotherapy explored to combine the anti‐cancer effect of phototherapy with the immune enhancement ability of immunotherapy, and shown great prospects for cancer treatment strategies. However, photomediated immunotherapy triggered antitumor immunity through the release of tumor antigens and damage‐associated molecular patterns from necrotic tumor cells was not enough mighty to improve the therapeutic benefits due to the immunosuppressive tumor microenvironments. Herein, a tumor‐targeted nano‐adjuvant Fucoidan@Al(OH)3‐Poly(I:C)/IR‐820 for tumor‐targeted therapy and metastasis inhibition was designed and prepared. The intrinsic immunomodulatory effects of tumor‐targeted nano‐adjuvant and their ability to simultaneously trigger tumor antigen release, thereby reversing immunosuppression and achieving potent antitumor immunity and augmented cancer therapy, were explored. The results proved that the multifunctional nano‐adjuvant combined with photothermal, photodynamic, and immunotherapy could effectively treat breast cancer and had metastasis inhibition effect by enhancing anti‐tumor immunity through immunomodulation, it should have great application potential in the treatment of breast cancer.

Abstract Background To investigate the effects of autologous meniscus fragment (AMF) implantation on injury in the meniscal avascular zone in mature rabbits. Methods Adult New Zealand white rabbits were randomly divided into two groups. Massive one-piece meniscus tissue was implanted in situ as control. In the experimental group, AMF was used to repair the meniscal injury in the avascular zone. Meniscal damage was assessed by gross observation of the degree of healing and histological semi-quantitative evaluation within 12 weeks postoperatively. The healing of meniscus interface was assessed by gross observation semiquantitative scoring and microscopic examination hematoxylin and eosin (H&E) staining at 2, 4, 8, and 12 weeks after surgery. The expressions of proliferating cell nuclear antigen (PCNA), collagen type I (COL1A1), and collagen type II (COL2) were detected by immunohistochemical staining. Results The degree of healing in the AMF group showed a significant increase over time (P

AIM: To explore the clinical effect and safety of deep lateral wall combined with medial wall orbital decompression in the treatment of thyroid associated ophthalmopathy(TAO).METHODS: Totally 17 patients with TAO in our department from January 2019 to May 2020 were included. All patients underwent deep lateral wall combined with medial wall orbital decompression under general anesthesia, the visual acuity, recovery of exposure keratitis, exophthalmos, intraocular pressure and complications were compared before and after operation.RESULTS: Eight patients(9 eyes)with TAO and dysthyroid optic neuropathy(DON)were included in the study. The best corrected visual acuity averaged 0.78±0.15 preoperatively and 0.36±0.12 1mo postoperatively, which was statistically significant(P

Cancer-associated fibroblasts (CAFs) are a major contributor to tumor stromal crosstalk in the tumor microenvironment (TME) and boost tumor progression by promoting angiogenesis and lymphangiogenesis. This study aimed to identify prognostic genes associated with CAFs that lead to high morbidity and mortality in ovarian cancer (OC) patients. We performed bioinformatics analysis in 16 multicenter studies (2,742 patients) and identified CAF-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify COL16A1, COL5A2, GREM1, LUM, SRPX, and TIMP3 and construct a prognostic signature. Subsequently, a series of bioinformatics algorithms indicated risk stratification based on the above signature, suggesting that high-risk patients have a worse prognosis, weaker immune response, and lower tumor mutational burden (TMB) status but may be more sensitive to routine chemotherapeutic agents. Finally, we characterized prognostic markers using cell lines, immunohistochemistry, and single-cell sequencing. In conclusion, these results suggest that the CAF-related signature may be a novel pretreatment guide for anti-CAFs, and prognostic markers in CAFs may be potential therapeutic targets to inhibit OC progression.

AIM:To investigate the clinical effect of rectus muscle release and recession combined with orbital fat resection on restrictive strabismus of thyroid associated ophthalmopathy.METHODS: From March 2018 to June 2019, 27 cases of restrictive strabismus with thyroid associated ophthalmopathy were retrospectively analyzed, 34 eyes in total. Under general anesthesia, all patients underwent rectus muscle release and orbital fat resection. The range of orbital fat resection was selected according to the degree of the ophthalmologic process in the subnasal, subtemporal, superior nasal, or superior temporal quadrants.Inferior rectus recession was performed in 25 eyes, medial rectus recession in 5 eyes and superior rectus recession in 4 eyes. According to the degree of exophthalmos, he internal and external fat of inferior nasal, infratemporal, Supranasal or supratemporal quadrant muscles were excised respectively during the operation. According to the preoperative strabismus degree and the degree of contraction of external rectus muscle, the recession amount of rectus operation was designed,and the strength of passive rotation test was estimated intraoperatively. The amount of fat removed during the operation was designed according to the degree of protrusion before operation, and it was designed to remove about 1mL fat and retract the eyeball by 1mm.The postoperative follow-up time was once a week, once a month after 1mo, and irregular follow-up after 3mo. All patients were followed up for more than 6mo.RESULTS: The amount of fat removed was 2.1-3.4mL, with an average of 2.6mL.The visual(LogMAR)acuity was 0-0.2 in the 1mo after operation, with an average of 0.11±0.16. The visual acuity was 0-0.3 in the 6mo after operation, with an average of 0.12±0.17.There was no significant difference in visual acuity before and after operation(P>0.05). The degree of eyeball protrusion was 13-16mm, with an average of 14.4±0.8mm, and the degree of corrected eyeball protrusion was 2-4mm, with an average of 2.4mm(q=10.737, Pq=0.624, P=0.173). 1mo after surgery, the strabismus was 2△-10△, with an average of 6.7△±2.3△, all of which were under correction(q=18.068, P△-7△, with an average of 3.4△±1.2△, and the difference was statistically significant compared with 1mo after surgery(q=5.385, P=0.015). The patient had no diplopia at the first and lower transitory position. The mean intraocular pressure after surgery(17.12±1.89mmHg)was lower than that before surgery, and the difference between preoperative and postoperative intraocular pressure was statistically significant(q=4.258, P=0.018).The mean intraocular pressure at 6mo after surgery was 17.53±1.67mmHg, with no significant difference from 1mo after surgery(q=0.729, P=0.154).CONCLUSION: Orbital fat resection can improve the protrusion of the eyeball, but has no significant influence on the surgical design and effect of restrictive strabismus. It is a kind of controllable operation scheme to treat the limited strabismus with exophthalmos of thyroid associated ophthalmopathy with rectus muscle release and recession combined with orbital fat resection.

The zebrafish as an alternative animal model for developmental toxicity testing has been extensively investigated, but its assay protocol was not harmonized yet. This study has validated and optimized the zebrafish developmental toxicity assay previously reported by multiple inter-laboratory studies in the United States and Europe. In this study, using this classical protocol, of 31 ICH-positive compounds, 23 compounds (74.2%) were teratogenic in zebrafish, five had false-negative results, and three were neither teratogenic nor non-teratogenic according to the protocol standard; of 14 ICH-negative compounds, 12 compounds (85.7%) were non-teratogenic in zebrafish and two had false-positive results. After we added an additional TI value in the zebrafish treated with testing compounds at 2 dpf along with the original 5 dpf, proposed a new category as the uncategorized compounds for those TI values smaller than the cutoff both at 2 dpf and 5 dpf but inducing toxic phenotypes, refined the testing concentration ranges, and optimized the TI cut-off value from ≥ 10 to ≥ 3 for compounds with refined testing concentrations, this optimized zebrafish developmental assay reached 90.3% sensitivity (28/31 positive compounds were teratogenic in zebrafish) and 88.9% (40/45) overall predictability. Our results from this study strongly support the use of zebrafish as an alternative in vivo method for screening and assessing the teratogenicity of candidate drugs for regulatory acceptance.

Background: The ketogenic diet (KD) has been reported to play an important role in the development of cancer by an abundance of pre-clinical experiments; however, their conclusions have been controversial. We therefore aimed to perform a systematic review and meta-analysis of animal studies evaluating the effects of KD on cancer.Methods: Relevant studies were collected by searching PubMed, Embase, and Web of Science. Outcome measures comprised tumor weight, tumor volume, and survival time. Meta-analysis was performed using the random-effect model according to heterogeneity.Results: The search resulted in 1,254 references, of which 38 were included in the review and 17 included in the meta-analysis. Pooled results indicated that KD supplementation significantly prolonged survival time [standardized mean difference (SMD) = 1.76, 95% CI (0.58, 2.94), p = 0.003], and reduced tumor weight [SMD = −2.459, 95% CI (−4.188, −0.730), p = 0.027] and tumor volume [SMD = −0.759, 95% CI (−1.349, −0.168), p = 0.012]. Meta-regression and subgroup analysis results suggested that KD supplementation at a ratio of 4:1 was associated with remarkable prolongation of survival time in animals with limited tumor types.Conclusion: In summary, the pre-clinical evidence pointed toward an overall anti-tumor effect of the KD in animals studies currently available with limited tumor types.

AIM: To observe the clinical effect of external rectus muscle amputation in the treatment of divergence insufficiency. METHODS: A retrospective analysis of 37 cases of insufficiency in our hospital from February 2011 to October 2017. The clinical manifestations were hyperopic esotropia with ipsilateral diplopia, myopia implicit esotropia without diplopia, and the monocular and binocular movements were normal. Preoperative refractive, strabismus, near stereopsis, negative fusion force examination, and then single or double external rectus muscle surgery.RESULTS: Double vision disappeared after all cases, and there was no recurrence in diplopia after one year of follow-up. The preoperative long-term internal strabismus was +15△-+28△, with an average of 18.4△±5.7△, the near-internal strabismus was +5△-+16△, the average was 10.3△±3.6△, The difference value of long distance and short distance strabismus was 8.1△±2.3△; one week after surgery, the distance strabismus was -5.4△±1.5△, the near-distance squint was -7.2△±1.6△, the difference value was 1.8△±0.6△; the one year postoperative strabismus was -1.9△±1.2△, the close squint was -3.4△±1.4△, the difference value was 1.5△±0.8△. The long-distance strabismus one week after operation and one year after operation was significantly lower than that before operation(PP△-9△, with an average of 5.1△±1.8△, and the near-negative fusion force was 15△-24△, with an average of 19.4△±3.2△. The long-near negative fusion force was 10.1△±3.3△, 19.7△±4.1△ at 1wk after operation, and the long-distance negative fusion force was 11.2△±3.6△, 20.2△±4.8△ for one year after operation. There was a statistically significant difference between the patients with preoperative and one week postoperative negative fusion(q=4.551, P=0.013). There was no significant difference between the one week and one year after surgery(q=0.713, P=0.115).There was no significant difference in the patients' brachytherapy before and after one week and one year after operation(P>0.05).CONCLUSION: Divergence insufficiency of external rectus muscle surgery can effectively reduce the difference of long-distance strabismus after surgery, eliminate the symptoms of diplopia in patients, and improve the near stereoscopic sharpness and long-distance negative fusion force.