Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy.

Esophageal cancer (ESC) is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract. Although the exact pathogenesis of ESC has not been fully elucidated, excessive oxidative stress is an important characteristic that leads to the development of many cancers. Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs, which alters the growth and proliferation of ESCs and promotes their metastasis. Natural compounds, including alkaloids, terpenes, polyphenols, and xanthine compounds, can inhibit reactive oxygen species production in ESCs. These compounds reduce oxidative stress levels and subsequently inhibit the occurrence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10, superoxide dismutase, the NF-+ACY-kappa+ADs-B/MAPK pathway, and the mammalian Nrf2/ARE target pathway. Thus, targeting tumor oxidative stress has become a key focus in anti-ESC therapy. This review discusses the potential of Natural products (NPs) for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment. The findings of this review provide a reference for drug development targeting ESCs. Nonetheless, further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

Berberine: An inspiring resource for the treatment of colorectal diseases.

Colorectal cancer is a prevalent malignant tumor with a complex and diverse pathogenesis. In recent years, natural products have shown promising application prospects as sources of anticancer drugs. BBR, a class of benzoquinoline alkaloids extracted from various plants, is widely used in disease treatments owing to its pharmacological activities, including antibacterial, anti-inflammatory, antioxidant, anticancer, and anti-angiogenesis properties. Research has demonstrated that BBR exerts an anti-Salmonella and -Escherichia coli infection effect, attenuating inflammatory reactions by inhibiting harmful bacteria. During the stage of colorectal precancerous lesions, BBR inhibits the activity of cell cyclin by regulating the PI3K/AKT, MAPK, and Wnt signaling pathways, thereby decelerating the cell cycle progression of polyp or adenoma cells. Moreover, the inhibitory effect of BBR on colorectal cancer primarily occurs through the regulation of the cancer cell cycle, anti-angiogenesis, gut microbiota, and antioxidant pathways. The specific involved pathways include the MPK/ERK, NF-kB, and EGFR signaling pathways, encompassing the regulation of Bcl-2 family proteins, vascular endothelial growth factor, and superoxide dismutase. This study reviews and summarizes, for the first time, the specific mechanisms of action of BBR in the carcinogenesis process of colorectal cancer, providing novel insights for its clinical application in intestinal diseases.

Doxycycline vs Placebo at 12 Weeks in Patients With Mild Thyroid-Associated Ophthalmopathy: A Randomized Clinical Trial.

Importance: Mild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO. Objective: To evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO. Design, Setting, and Participants: In this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks. Interventions: Participants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks. Main Outcomes and Measures: The primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded. Results: A total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group. Conclusions and Relevance: The results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort. Trial Registration: ClinicalTrials.gov Identifier: NCT02203682.

Reconstruction of complex orbital fracture with titanium implants.

AIM: To evaluate the effectiveness and safety of complex orbital fracture reconstruction with titanium implants. METHODS: A retrospective review of 46 patients treated with complex orbital fractures reconstruction using titanium implants from January 2005 to December 2008 was conducted. The following data were recorded: age, gender, mechanism of injury, preoperative and postoperative orbital CT, visual acuity, diplopia, ocular motility and Hertel exophthalmometer. RESULTS: The most common cause was motor vehicle accident (47.8%), followed by industrial injury (30.4%). All patients had improved appearance after operation and CT scan at one week after operation showed the fracture defects of orbit and neighboring areas had been reconstructed. Forty-six cases had various degrees of enophthalmos before operation. Among them, 32 cases were completely corrected, 11 cases improved obviously and 3 cases had no improvement after operation. Thirty-six patients with visual acuity ≥20/60 revealed diplopia of various degrees, including 26 patients had diplopia in right ahead and/or reading positions. At the sixth month after operation, diplopia disappeared in five patients, 7 patients still had diplopia in right ahead and/or reading positions, 14 patients had diplopia in positions rather than right ahead and reading positions (<20°) and ten patients had diplopia only at peripheral gazing (>20°). All patients had various degrees of ocular motility disorders before operation. At the sixth month after operation, eyeball movement disorder disappeared in 9 patients, 31 patients showed improvement and 6 patients had no improvement. Complications of implant infection, rejection and displacement were not reported after operation. CONCLUSION: The application of titanium implants in the repair of complex orbital fractures greatly improves the appearance and functional results, which is a favorable material for plastic surgery of complex orbital fracture.

Transcranial surgery through pterional approach for removal of cranio-orbital tumors by an interdisciplinary team of nurosurgeons and ophthalmologists.

AIM: To investigate the specialty of transcranial surgery through pterional approach for removal of cranio-orbital tumors, introduce the ophthalmological experiences of entering the orbit to reduce the incidence rate of associated complications of this operation. METHODS: We performed a retrospective analysis of a series of 37 cases involving patients who underwent transcranial surgery through pterional approach for treatment of cranio-orbital tumors in our department in the past 8 years. Pterion approach craniotomy was performed to all patients. After removing tumors in the skull by the neurosurgeon, ophthalmologist removed tumors in orbit. We took measures below to decrease complications, including grounding optic canal through an abrasive drilling when necessary, hanging various extraocular muscles to be exposed for protection, refrigerating by refrigeration heads to remove tumors, at last sewing up orbit septum after surgery. RESULTS: Tumors were removed completely in 32 cases, and incomplete in 5 cases due to extensive invasion into the cavernous sinus or sphenoid sinus. Of all the cases, benign tumors were demonstrated in 28 cases (75.6%, 28/37) and malignant in 9(24.3%, 9/37). The most common lesion type was meningioma in 11 cases (29.7%, 11/37). Extraocular muscles (EOM) impairment, occurring in 21 cases (56.7%, 21/37), was the most frequent postoperative complication. The most serious consequence was vision loss occurred in 4 cases (10.8%, 4/37). Other complications, such as 11 cases of transient blepharoptosis 29.7% (11/37), 5 cases of mydriasis in 13.5% (5/7); 2 cases of cerebrospinal rhinorrhea in 5.4% (2/37). CONCLUSION: Cranio-orbital tumors can be removed completely using transcranial approach, and the pterional approach offers excellent exposure. Cooperation of interdisciplinary team of neurosurgeons and ophthalmologists conduces to full use of respective professional advantages. The experience of ophthalmic operation technology can decrease occurrence of ocular complications after surgery.

[Effects of LPS-induced inflammation on differentiation of orbital pre-adipocytes in thyroid-associated ophthalmopathy].

OBJECTIVE: To investigate the effects of lipopolysaccharide (LPS)-induced inflammation on the differentiation of orbital pre-adipocytes in thyroid-associated ophthalmopathy (TAO) and to explore the mechanism of orbital adipose proliferation in TAO. METHODS: Orbital adipose tissues were obtained from patients with TAO undergoing orbital decompression surgery. The orbital fibroblasts cultured from orbital adipose tissues were divided into group A and group B. In group A, orbital pre-adipocytes were incubated in culture medium containing 1 mg/L LPS for 8 hours before stimulated to differentiate into mature adipocytes with Differentiation Medium I and II. No LPS or other intervention was used in group B before induced to differentiate into mature adipocyte with Differentiation Medium I and II. Intracellular fat accumulation in differentiated adipocytes was determined by oil red O staining and the expression of cyclooxygenase2 (COX2) and peroxisome proliferators activated receptor γ (PPARγ) mRNA of both groups were detected by RT-PCR. Protein expression of COX2 and PPARγ in both groups was detected by Western-blot and the secretion of PGE(2) in the supernatant was detected by ELISA. RESULTS: COX2 expression and secretion of PGE(2) in differentiated cells of both groups were significantly decreased compared with pre-differentiation (P < 0.05), while PPARγ mRNA and protein expression enhanced significantly (P < 0.05). COX2 mRNA and protein expression and secretion of PGE(2) of pre-differentiation cells in group A was significantly increased compared with group B (P < 0.05), while PPARγ mRNA and protein expression in group A was also stronger than those in the group B (P < 0.05). COX2 and PPARγ mRNA and protein expression and secretion of PGE(2) of differentiated cells in group A were greater than those in group B (P < 0.05). CONCLUSION: LPS can induce inflammatory response of orbital preadipocytes in TAO and enhance the expression of COX2, PPARγ and PGE(2). The expression of PPARγ is enhanced significantly while the expression of COX2 and PGE(2) is attenuated markedly when the orbital pre-adipocytes differentiated into adipocytes.

Role of unc5b in retinal neovascularization in mice with oxygen-induced retinopathy.

AIM: To explore the role of unc5b in retinal neovascularization in murine oxygen-induced retinopathy (OIR). METHODS: On postnatal 7(P7), C57BL/6J mice were exposed to 75%±2% oxygen for 5 days. On postnatal 12(P12), the mice were brought back to the room air (21% oxygen) to induce retinal neovascularization. Western blot analysis was performed to examine the temporal expression of unc5b in murine retinas. Double staining for unc5b and isolectin B4 were employed to determine the location of unc5b in murine retinas. The effect of unc5b on retinal neovascularization was evaluated by intravitreal injection of unc5b-FC in mice with OIR. Retinal neovascularization was measured by counting neovascular cell nuclei above the internal limiting membrane and by angiography of flat-mounted retinas perfused with fluorescein dextran. RESULTS: Compared to age-matched normal mice, the expression of unc5b was significantly increased in retinas of OIR mice on P17 and P21. Unc5b was apparently expressed in retinal vessels of OIR while being negative in normal retinal vessels. Retinal neovascularization in eyes injected with unc5b-FC was significantly reduced. CONCLUSION: Unc5b-FC can effectively inhibit retinal neovascularization induced by OIR. It may serve as a powerful and novel therapy for ischemia-induced retinal disease.

[Suture-fixation of foldable Akreos intraocular lens by two-point on sclera and four-haptic of the lens].

OBJECTIVE: To evaluate the therapeutic efficacy of suture-fixation of foldable intraocular lens for non-posterior-capsular aphakia. METHODS: Akreos intraocular lens (from Bausch-Lamb Company) were selected for operation in aphakia with non-posterior-capsule or less capsule supporting intraocular lens. Complications and visual acuity were observed. RESULTS: There was no significant complication in the operation. Choroidal detachment occurred in 2 eyes postoperatively. Visual acuity of 0.3 accounted for 56.67%, 76.67%, 86.67%, and 90% respectively on the first day, at 1 week, 1 month and 3 months after the operation. CONCLUSION: Suture-fixation of Akreos intraocular lens is a good choice for non-posterior-capsular aphakia.

[Characteristics of ocular adnexal non-Hodgkin lymphoma].

OBJECTIVE: To investigate the clinical manifestation and pathological features of primary ocular adnexal non-Hodgkin lymphoma. METHODS: Data of 18 patients with biopsy-proven ocular adnexal non-Hodgkin lymphoma at Xiangya hospital were reviewed.The disease site, clinical manifestation,imaging and pathological features of the tumor were summarized. RESULTS: All patients had typical presentation of an adnexal mass.Twelve(66.7%) patients had orbital involvement, 3(16.7%) had conjunctival, and 3(16.7%) had lymphoma involving the eyelids.Eight patients were misdiagnosed as "inflammatory pseudotumour" before the operation according to their clinical and imaging examination,another 8 patients were diagnosed as "ocular adnexal tumour with unknown nature" before the operation. According to the pathologic diagnosis, 16 patients (88.9%)had marginal zone lymphomas of mucosa-associated lymphoid tissue(MZL-MALT) and 2 (11.1%) had NK/T-cell lymphoma. CONCLUSION: The typical presentation of ocular adnexal lymphoma is a painless mass.Orbital connective tissue is the most involved anatomical site. The diagnosis of ocular adnexal non-Hodgkin lymphoma is difficult which could easily be misdiagnosed as "inflammatory pseudotumour". MZL-MALT is the most common pathologic type.

[Histopathologic and ultrastructural study of extraocular muscles in thyroid associated ophthalmopathy].

OBJECTIVE: To investigate histopathologic and ultrastructural changes of extraocular muscles (EOM) in thyroid associated ophthalmopathy (TAO). METHODS: Twelve EOM specimens from 11 patients with TAO were observed. Each of the specimen was stained with HE and observed by light microscope,and then was sectioned with ultrathin method and observed by transmission electronic microscope. RESULTS: Under the light microscope, sarcoplasm coagulation,granular degeneration, vacuolization and necrosis were found in the extraocular muscular cells.Under the electronic microscope, there were disturbance and disappearance of the Z line in part of muscular fibers and various degrees of sarcoplasmic reticulum dilatation, myofilament lysis and destruction with formation of vacuoles.In severe cases,the muscular cells could be completely destroyed and phagocytosed by macrophages,fibrosis occurred and myofibroblasts were found in some cases. CONCLUSION: The extraocular muscles in TAO are destroyed at various degrees,and the muscular cells may be the target cells in TAO.

[Transconjunctival surgical cryoextraction of introconal orbital cavernous hemangiomas].

OBJECTIVE: To evaluate the Methods , complication and operative skill in transconjunctival surgical cryoextraction of intraconal orbital cavernous hemangioma. METHODS: Among the 41 patients diagnosed as orbital cavernous hemangioma preoperatively, 36 suitable for the condition were treated with the operation. The operation time was recorded, and the complications were observed during and after the operation. RESULTS: The tumours of the 36 patients were all excised successfully, of which 35 were diagnosed as orbital cavernous hemangioma, and the other 1 as neurilemoma post-operatively. The operation time of each was 20 to approximately 25 min and there was no perpetual complications. CONCLUSION: Transconjunctival surgical cryoextraction of intraconal orbital cavernous hemangioma is simple, swift, safe and effective with tiny injury.

[Cell surface antigen expression of orbital preadipocytes between patients with thyroid-associated ophthalmopathy and healthy adults].

OBJECTIVE: To study the cell surface antigen expression of orbital preadipocytes between patients with thyroid-associated ophthalmopathy (TAO) and healthy adults. METHODS: Tissue culture Methods were used in the cell culture of orbital preadipocytes in patients with TAO and healthy adults. Flow cytometry was used to analyze the expression of CD29, CD44, CD49d, and HLA-DR in these 2 cells. RESULTS: Positive expressions were examined in orbital preadipocytes of patients with TAO and healthy adults. The orbital preadipocytes of patients with TAO had a higher expression of HLA-DR than that of healthy adults. CONCLUSION: The orbital preadipocytes of patients with TAO and healthy adults cultured by tissue cultured Methods both belong to mesenchymal stem cells, and the former may participate in the orbital inflammation.

[Transcranial operation for cranio-orbital communicating tumors and its complications].

OBJECTIVE: To investigate the procedure of transcranial operation via pterional approach for cranio-orbital communicating tumors, to improve surgery skills, to summarize the incidence of main complications and to discuss tips for avoiding damage of the normal orbital tissues. METHODS: Pterional approach was adopted for the operation. After the medial orbital wall or lateral orbital wall was bitten with rongeur and the orbital roof was removed, the extraocular muscles at orbital apex were separated and protected. The head of condenser was used to freeze the tumor, and the tissue around the tumor was separated until the tumor was extirpated. In cases where the tumor penetrated the dura mater and invaded the brain, surgery was performed by neurosurgeons. RESULTS: In 37 cases, 32 cases undertook total resection of tumors and palliative resection was performed in 5 cases due to severe tumor invasion of the cavernous sinus or sphenoid sinus. Of the 37 cases, 28 cases were benign tumors and accounted for 75.67% of total cases (28/37); 9 were malignant tumors and accounted for 24.32% (9/37). Pathological examination showed that 11 cases were meningioma which was the most common type of tumor and accounted for 29.73% of total cases(11/37). The most common complication was injury to extraocular muscles, which occurred in 21 cases and accounted for 56.76% of all cases (21/37). The most serious complication was vision loss, which occurred in 4 cases and accounted for 10.81% of all cases (4/37). CONCLUSIONS: Resection of cranio-orbital communicating tumors via pterional approach provides a wide observation field and facilities exposing tumors. Protecting important tissues in posterior orbital region will result in less postoperative complications.

[Clinical effects of the mixture of 5-fluorouracil and triamcinolone acetonide on capillary hemangioma of eyelid].

OBJECTIVE: To evaluate the clinical effects of the mixture of 5-fluorouracil (5-FU) and triamcinolone acetonide on capillary hemangioma of eyelid. METHODS: One hundred and one patients with capillary hemangioma of eyelid were divided into Group A and Group B: Group A was injected with triamcinolone acetonide, and Group B was injected the mixture of 5-FU and triamcinolone acetonide. RESULTS: The cure rate was 68.3%, the total effective rate was 76.0%, and the average course of treatment was (8.1+/-3.4) months for Group A; the cure rate was 90.0%, the total effective rate was 96.6%, and the average course of treatment was (5.1+/-2.3) months for Group B. The therapeutic effect in Group B was better than that in Group A (P<0.05). The treatment period in Group B was shorter than that in Group A (P<0.05). CONCLUSION: 5-FU combining with triamcinolone acetonide has not only a better therapeutic effect, but also a shorter period of treatment.

[Cataract extraction through no-sitch small incision combined with intraocular lens implantation].

OBJECTIVE: To investigate the method and clinical effect of cataract extraction through no-sitch small incision combined with intraocular lens (IOL) implantation. METHODS: Ninety-three cases of cataract were divided into two groups at random. Cataract extraction combined with IOL implantation through no-sitch small incision was performed on one group, and cataract extraction combined with IOL implantation through conventional large incision was performed on the other group as controls. Follow-up was carried out regularly. RESULTS: The average uncorrected visual acuity of the small incision group at 1 week, 1 month, 3 months, 6 months and 1 year after the operation were significantly higher than those of the conventional large incision group. CONCLUSION: The small incision of cataract surgery results in a rapid and better rehabilitation of visual acuity. It needs no expensive instruments, costs less, and is suitable to be popularized.