[The efficacy and safety of immunotherapy combined with chemotherapy neoadjuvant in locally advanced resectable hypopharyngeal squamous cell carcinoma].

Objective: To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients. Methods: This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy. Results: By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence. Conclusions: The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

[Later approach sinus floor elevation using deproteinized bovine bone mineral with staged implant placement: follow-up for more than 3 years in a prospective clinical study].

Objective: To evaluate clinical effect of deproteinized bovine bone for delayed implantation after fenestration. Methods: This trial is a continuation of a prospective clinical trial. From May 2011 to February 2015 in Department of Implantology, School of Stomatology, The Fourth Military Medical University after planting division of 55 cases of maxillary teeth missing area of residual alveolar bone height ≤5 mm patients. There were 21 female and 34 male patients, their average age were (55.2±7.1) years. A total of 62 side fenestration of maxillary sinus floor lift, clinical and imaging examination, evaluation of implant retention rate, complications, peripheral soft tissue health and marginal bone resorption. Results: A total of 82 implants were followed up in 41 patients. The average follow-up time was (51.8±14.3) months (36-78 months). The follow-up rate of the maxillary sinus was 75.8% (47/62), the follow-up rate of the implant was 73.9% (82/111), and the implant survival rate was 98.8% (81/82). The bone resorption results at the implant margins were (0.64±0.63) mm (-0.28 mm, 1.47 mm) in the near and (0.49±0.73) mm (-0.51 mm, 1.21 mm) in the far, the improved hemorrhage index was 0.46±0.72, the improved plaque index was 0.60±0.87, and the keratinized mucosa width was (2.14±1.22) mm. The incidence rate of peri-implant mucositis was 28.4% (23/81) among 23 implants, and there was no complication of peri-implant inflammation. Conclusions: This study shows that under the condition of insufficient sinus ridge spacing in the maxillary posterior area, it is feasible to use bovine bone alone to remove protein for delayed implantation of maxillary sinus floor elevation by windowing, and the clinical effect is reliable.

[Evidence-based evaluation of recent clinical practice guidelines for the diagnosis and treatment of benign prostatic hyperplasia].

Objective: To systematically evaluate the quality of clinical practice guidelines for the diagnosis and treatment of benign prostatic hyperplasia (BPH), and to compare the context of recommendations in order to provide references for clinical application. Methods: We searched databases such as the National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and World Health Organization (WHO), PubMed, Embase, CNKI, VIP, WanFang Data, CBM, and Medlive from their establishment until August 13, 2016, to collect evidence-based guidelines and/or consensus on BPH. Method: Methodological quality of included guidelines was assessed according to the AGREE Ⅱ instrument, and differences and similarities among recommendations were compared. Results: A total of 15 guidelines were included. According to the AGREE Ⅱ instrument, the score of scope and purpose, stakeholder involvement, rigour of formulate, clarity of presentation, applicability, and editorial independence was 72%, 38%, 30%, 58%, 16%, and 40%, respectively. The recommendations of different guidelines were basically similar, only with conflicts in some areas. Conclusions: The quality of included guidelines remains to be unified, the context of them can provide valuable implications for development or improvement.

The M2 macrophages induce autophagic vascular disorder and promote mouse sensitivity to urethane-related lung carcinogenesis.

Tumor vessels are known to be abnormal, with typically aberrant, leaky and disordered vessels. Here, we investigated whether polarized macrophage phenotypes are involved in tumor abnormal angiogenesis and what is its mechanism. We found that there was no difference in chemotaxis of polarized M1 and M2 macrophages to lewis lung carcinoma (LLC) cells and that either M1 or M2 macrophage-conditioned media had no effect on LLC cell proliferation. Unexpectedly, the M2 but not M1 macrophage-conditioned media promoted the proliferation of human umbilical vein endothelial cells (HUVECs) and simultaneously increased endothelial cell permeability in vitro and angiogenic index in the chick embryo chorioallantoic membrane (CAM). The treatment with M2 but not M1 macrophage-conditioned media increased autophagosomes as well as microtubule-associated protein light chain 3B (LC3-B) expression (a robust marker of autophagosomes) but decreased p62 protein expression (a selective autophagy substrate) in HUVECs, the treatment with chloroquine that blocked autophagy abrogated the abnormal angiogenic efficacy of M2 macrophage-conditioned media. These results were confirmed in urethane-induced lung carcinogenic progression. Urethane-induced lung carcinogenesis led to more M2 macrophage phenotype and increased abnormal angiogenesis concomitant with the upregulation of LC3-B and the downregulation of p62. Clodronate liposome-induced macrophage depletion, chloroquine-induced autophagic prevention or salvianolic acid B-induced vascular protection decreased abnormal angiogenesis and lung carcinogenesis. In addition, we found that the tendency of age-related M2 macrophage polarization also promoted vascular permeability and carcinogenesis in urethane carcinogenic progression. These findings indicate that the M2 macrophages induce autophagic vascular disorder to promote lung cancer progression, and the autophagy improvement represents an efficacious strategy for abnormal angiogenesis and cancer prevention.

Microsurgery for the treatment of primary malignant intracranial melanoma: a surgical series and literature review.

BACKGROUND: Primary malignant intracranial melanomas are rare tumors of the central nervous system. These tumors are highly malignant and are associated with poor prognosis. The field of neurosurgery has struggled with the diagnosis and treatment of these tumors. METHODS: In this study, we present a surgical series of eight patients with primary malignant intracranial melanomas and retrospectively analyze the clinical features, imaging findings, pathological features and prognoses of these patients. RESULTS: All patients underwent microsurgery. Total and subtotal resection of the tumor was achieved in six and two patients, respectively. Of the eight patients, seven showed improvement while one remained the same at time of discharge. There was no neurosurgical deterioration. Radiotherapy was conducted in six patients after operation. The average follow-up duration was 13.8 months (range = 9-26 months). During the follow-up period, three patients died from this disease. One patient suffered from recurrence at the 16th month and underwent second surgery. The other patients were still alive with no evidence of tumor recurrence. CONCLUSION: Microsurgery and radiotherapy should be the first line managements for patients with primary malignant intracranial melanomas. Improvements in chemotherapy, immunotherapy and targeted therapies may provide more effective treatments for malignant intracranial melanomas.

Damage spreading in two-dimensional trivalent cellular structures with competing Glauber and Kawasaki dynamics.

The damage spreading of the Ising model on several two-dimensional trivalent structures, including soap froth, Voronoi, and hierarchical structures, are studied with competing Glauber and Kawasaki dynamics. The damage spreading transition temperature T(d) and the Curie temperature T(C) of these structures are compared. We find that T(d) of the hierarchical lattices decreases sharply as the probability of occurrence of Kawasaki dynamics increases, whereas for soap froth and Voronoi, T(d) for the Voronoi and soap froth remain nearly unchanged except when the dynamics is dominated by Kawasaki dynamics. T(d) and T(C) in our two-dimensional structures are nearly the same and they behave similarly as we change the relative probability of occurrence of the Glauber and Kawasaki dynamics. A heuristic argument is provided to explain the numerical results.

Damage spreading on two-dimensional trivalent structures with Glauber dynamics: hierarchical and random lattices.

The damage spreading of the Ising model on various two-dimensional trivalent structures with Glauber dynamics is investigated. It is shown that topology plays an important role in determining the damage spreading transition temperatures of the trivalent structures. When damage is considered in terms of only the topological properties of the cellular patterns, the transition temperature above which damage is saturated is found to be determined by the cells with the highest edge number. When the area of cells is also taken into account in the computation of damage, the damage spreading transition temperatures are all lowered. These results are verified by simulation on a set of hierarchical lattices constructed by recursive application of the star-triangle transformation on the vertices of the hexagonal structure, as well as soap froth and randomized lattice structures using Voronoi construction.

[Application of the polymerase chain reaction to the epidemiological study of amoebiasis].

The polymerase chain reaction (PCR) has been used in studying the pathogenicity of Entamoeba histolytica in a rural community in Shandong province. Formalin-fixed stool samples were used for extraction of DNA. The PCR amplifications were performed using two sets of primer that discriminate between pathogenic and nonpathogenic E. histolytica. All of the 32 cases of cyst carrier diagnosed microscopically were identified as positive. Three groups were defined through PCR analysis: 6 cases (18.8%) were positive for pathogenic but negative for nonpathogenic, 25 cases (78.1%) were negative for pathogenic but positive for nonpathogenic, and only one case (3.1%) was positive for both pathogenic and nonpathogenic. The cases found to be pathogenic by PCR were also closely correlated with their clinical manifestations (diarrhea) (OR = 31.5, P < 0.005). All of the control cases showed negative reaction to PCR. PCR has also been used to study the epidemiology of amoebiasis in a small population group with 40 persons in the same province. Both positive rates by PCR on pathogenic and nonpathogenic were 10%. The results showed that this new technique can be applied in the field for the epidemiological studies of pathogenic and nonpathogenic E. histolytica.

Lipid peroxides, glutathione peroxidase, prostacyclin and cell cycle stages in normal and atherosclerotic Japanese quail arteries.

We have previously shown a negative correlation between lipid peroxide levels and prostacyclin synthesis in plasma and artery of the atherosclerotic rabbit. Here we compare the arterial lipid peroxide content, glutathione peroxidase activity, and prostacyclin and thromboxane production in response to exogenous arachidonic acid stimulation, and the cell cycle stages in normal and atherogenic diet-fed quail. Lipid peroxides were higher in arteries of the atherosclerotic quail, while glutathione peroxidase activity and prostacyclin and thromboxane production were lower than that in the control quail. The smooth muscle cell cycle distribution which was determined by flow cytometry according to DNA content showed that more than 14% of atherosclerotic arteries were mitotically active (in S + G2 + M phase), while less than 10% of control cells were active. These results suggest that there is a close relationship between lipid peroxide content, prostacyclin production and cell proliferation of the arterial wall in experimental atherosclerotic quail.

Effect of hyperlipidemic serum on lipid peroxidation, synthesis of prostacyclin and thromboxane by cultured endothelial cells: protective effect of antioxidants.

An increased lipid peroxides and a decreased production of prostacyclin have been shown in advanced atherosclerotic lesions and plasma. Our purpose was to determine whether the similar findings could be observed in cultured endothelial cells, and whether antioxidants could protect the cell against peroxide injury. In these experiments we have used bovine aortic endothelial cells in culture to address the issue of hyperlipidemia-induced arterial damage. Results of the present study showed that different concentration of hyperlipidemic sera from atherogenic rabbits induced a time- and dose-dependent alteration in the production of prostacyclin and levels of lipid peroxides in endothelial cells. Endothelial cells incubated with hyperlipidemic serum increased prostacyclin generation significantly during the initial stages and then continuously decreased. When endothelial cells were incubated for 36 h, TXA2 generation was also impaired and at the same time the cellular lipid peroxides content increased. There was a positive correlation between the concentration of hyperlipidemic serum and lipid peroxides and an inverse correlation with prostacyclin synthesis. The medium supplemented with antioxidant selenium or vitamin E showed a significant decrease in lipid peroxides and an increase in prostacyclin synthesis. These results suggest that both hyperlipidemic serum and lipid peroxides injury endothelial cells and inactivate prostacyclin synthetase, resulting in a decrease of prostacyclin production, while antioxidants have a protective effect. We conclude that the increase in lipid peroxides in association with hyperlipidemia results in alteration of prostacyclin synthesis that may play an important role in the pathogenesis of atherosclerosis.

Effects of lipid peroxides on prostacyclin and thromboxane generation in hypercholesterolemic rabbits.

Rabbits fed an atherogenic diet for 60 days resulted in high levels of plasma lipid peroxides as well as extreme hypercholesterolemia. Both levels stayed high until 35 days after the atherogenic diet stopped. At the same time, plasma PGI2 level was remarkably decreased while TXA2 and platelet aggregability were increased. Atherosclerotic aortas contain high levels of lipid peroxides associated with decreased PGI2 and increased TXA2 generation. Atherosclerotic plaques had the highest level of lipid peroxides and TXA2 while PGI2 production was the least, as compared with nonplaque tissue of the same artery and the normal arteries. The condition of normal arteries was just the reverse. There was a negative correlation between lipid peroxides and prostacyclin production, and a positive correlation between lipid peroxides and TXA2, in both plasma and aorta of rabbits. These results suggest that there is a close correlation between atherosclerosis, elevated lipid peroxides, and disturbances in PGI2/TXA2 balances.