SARS-CoV-2 Mpro inhibitors with antiviral activity in a transgenic mouse model.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.

[Transplantation of autologous labial salivary glands for severe dry eye].

OBJECTIVE: Autologous labial salivary gland transplantation has been a promising alternative for the treatment of severe dry eye. In this article, we describe the results of the ocular surface changes after labial salivary gland transplantation and investigate the feasibility of this treatment. METHODS: The results of this technique in 8 patients (eyes) who suffered from severe dry eye were prospectively analyzed after surgery (follow-up of 6 months). The best-corrected visual acuity, Schirmer I test, degree of discomfort, usage of pharmaceutical tear substitutes, tear interferometry and slit lamp examination were investigated at different time before and after surgery. RESULTS: All grafts remained viable and the survival rate is 100%. All patients showed significant increase in the Schirmer's test and they expressed great improvement in their ocular discomfort. The use of artificial tear substitutes was reduced because of the increased ocular surface lubrication. CONCLUSION: Although the authors' long-term experience still is limited, we believe that the procedure is a promising alternative approach for severe dry eye.

Microanatomic study of the vascular and duct system of the submandibular gland.

PURPOSE: Autologous microvascular submandibular gland (SMG) transfer is an effective treatment for severe keratoconjunctivitis sicca (KCS). However, epiphora (excessive tear secretion) may occur after the successful transfer of whole submandibular gland because tear secretion level is closely related to the size of the transferred gland. The aim of this study was to investigate the microanatomy of SMG to explore the possibility of partial SMG transfer to prevent postoperative epiphora. MATERIALS AND METHODS: Sixty intact and histologically normal human SMGs from patients with benign tumor of the mandible who underwent vascularized mandibular reconstruction and removal of the SMG for anastomosis of the blood vessels were included in the study. SMGs were perfused with methacrylate to form resin casts of blood vessels and ducts. The length and diameter of the blood vessels and ducts in the casts were measured using a sliding caliper. The numbers of lobules, distribution of arteries, veins, and ducts, as well as the relationship among them, were analyzed. RESULTS: The resin cast of the gland showed a treelike structure, with the vessels gradually dividing into multiple branches. The arteries, veins, and ducts run in parallel and were roughly divided into 3 levels: from the stem extending into the main branches (level I), into the narrower secondary branches (level II), and then the secondary branches subsequently divided into terminal branches (level III). The structures of the blood vessels and ducts were similar at each level in the lobules. In the vein casts, communicating vessels were found between the anterior facial vein and the concomitant vein of the facial artery. CONCLUSION: The characteristic treelike structure of the SMG vascular and ductal system may provide useful information for partial gland transfers.

[Evaluation of shear bond strengths of self-etching and total-etching dental adhesives to enamel and dentin].

OBJECTIVE: To evaluate the shear bond strengths of four dental adhesives in vitro. METHODS: The facial surfaces of 20 human maxillary incisors were prepared to expose fresh enamel and randomly divided into four groups, in each group 5 teeth were bonded with one adhesives: group A (Clearfil Protect Bond, self-etching two steps), group B (Adper( Prompt, self-etching one step), group C (SwissTEC SL Bond, total-etching two steps), group D (Single Bond, total-etching two steps). Shear bond strengths were determined using an universal testing machine after being stored in distilled water for 24 h at 37 degrees C. RESULTS: The bond strengths to enamel and dentin were (25.33 +/- 2.84) and (26.07 +/- 5.56) MPa in group A, (17.08 +/- 5.13) and (17.93 +/- 4.70) MPa in group B, (33.14 +/- 6.05) and (41.92 +/- 6.25) MPa in group C, (22.51 +/- 6.25) and (21.45 +/- 7.34) MPa in group D. Group C showed the highest and group B the lowest shear bond strength to enamel and dentin among the four groups. CONCLUSIONS: The two-step self-etching adhesive showed comparable shear bond strength to some of the total-etching adhesives and higher shear bond strength than one-step self-etching adhesive.

Anatomy of arteries and veins of submandibular glands.

BACKGROUND: Transplanting a vascularized autologous submandibular gland (SMG) is considered an effective method to treat severe keratoconjunctivitis sicca. But the operation may fail due to the anatomic variances in the blood vessels of SMG. The present study aimed to investigate the submandibular glands at the microanatomy level. METHODS: The microanatomy of blood vessels including arteries and veins of submandibular gland was investigated using 30 adult corpses and 60 submandibular glands were anatomized under a surgical microscope. The lengths and diameters of the arterial and venous glandular branches were measured using sliding caliper. RESULTS: The submandibular gland was mainly supplied by the facial artery and submental artery, partly by the lingual artery and external jugular artery. The venous drainage of the submandibualr gland occurred through the anterior facial vein, the venae comitantes of facial artery, the vein close to the Whaston's duct (the hilum vein), and seldom drained to external jugular vein and other veins. CONCLUSIONS: The anatomy of SMG is a complicated structure. Determining the main blood vessels of the submandibular gland is very important to achieve a successful vascularized autologous SMG transplant.

[Combination of transpalatal advancement pharyngoplasty and uvulopalatopharyngoplasty for obstructive sleep apnea].

OBJECTIVE: Investigate the response of the patients with obstructive sleep apnea hypopnea syndrome (OSAHS) patients to combination of transpalatal advancement pharyngoplasty and uvulopalatopharyngoplasty. METHODS: Thirty two patients with OSAHS, age ranged from 27 to 54, mean value (x +/- s) 39.1 +/- 7.8, male, body mass index (BMI) ranged from 22.9 to 36. 7 kg/m2, mean value (29.0 +/- 3.6) kg/m2, preoperative apnea and hypopnea index (AHI) was 11.7/h to 113.7/h, mean value (61.8 +/- 21.9)/h, the lowest blood oxygen saturation was 0.10 to 0.85, mean value 0.64 +/- 0. 13. With preoperative endoscopic technique, bony nasopharynx cavity narrowing were present, 14 patients had concomitant tonge-base obstruction. Cephalometric result, SNA ranged from 72.9 degrees to 87.0 degrees, mean value (80.7 +/- 4.1) degrees; SNB 69.50 to 85.0 degrees, mean value (76.8 +/- 4.5) degrees; PAS 0.5 cm to 2.1 cm, mean value (1.2 +/- 0.5) cm; MP-H: ranged from 1.2 cm to 3.5 cm, mean value (2.2 +/- 0.7) cm; PNS ranged from 2.4 cm to 3.5 cm, mean value (2.8 +/- 0.4) cm. All the patients had H-UPPP and concomitant transpalatal advancement pharyngoplasty. Fourteen patients with tonge-base obstruction had chin advancement. Results Six months after the operations, the patients were evaluated the response to the operations using Epworth sleep scale, OSAHS filtration questionnaire scale and polysomnography (PSG). There were 27 patients with the decrease percent of AHI reaching or more than 25% and 22 patients with the decrease percent of AHI reaching or more than 50% including 8 patients with AHI less than 5. The other 5 patients were ineffective. After operation, the Epworth sleep scale decreased from (9.2 +/- 4.5) to (4.7 +/- 2. 8) and OSAHS filtration questionnaire scale decreased form (56.0 +/- 15.3) to (17.5 +/- 11.5). Both of the differences were obvious (P < 0.01). CONCLUSIONS: Combination of transpalatal advancement pharyngoplasty and H-UPPP can improve the efficacity and in some patients with pure retropalatal airway narrowing, the cure rate can be improved.

[Protection of amrinone against lung injury induced by ischemia/reperfusion in rats].

OBJECTIVE: To investigate the protective effect of amrinone against experimental lung ischemia /reperfusion (I/R) injury. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 3 groups (n=8 each): sham- operated group, I/R group, and amrinone-treated I/R group (AMR group). The left lung of rats was subjected to ischemia for 90 minutes, followed by reperfusion for 2 hrs, to induce an I/R lung injury model. The rats of the AMR group received amrinone (10 mg/kg) intravenously 30 minutes before ischemia and 5 minutes before reperfusion. After 2 hrs of reperfusion, carotid artery blood was collected for blood-gas analysis and detection of serum levels of IL-1beta, IL-8 and TNF-alpha. The left lung was removed for detection of the lung wet/dry ratio, the erythrocuprein (SOD) activity and the malonaldehyde (MDA) content as well as the pathological changes. RESULTS: After 2 hrs of reperfusion, there were no significant differences in artery partial pressure of oxygen (PO2) and partial pressure of carbon dioxide (PCO2) among the three groups. The lung wet/dry ratio (5.3 +/- 0.5 vs 4.8 +/- 0.1) and the MDA content (0.66 +/- 0.16 nmol/mg prot vs 0.47 +/- 0.06 nmol/mg prot) in the I/R group were significantly higher than those of the sham-operated group (P <0.05). The administration of amrinone markedly reduced the lung wet/dry ratio (4.8 +/- 0.2) and the MDA content (0.51 +/- 0.09 nmol/mg prot) and increased the SOD activity (54.7 +/- 6.8 vs 39.3 +/- 3.0 U/mg prot) when comparing the I/R group (P < 0.05). The serum levels of IL-1beta, IL-8 and TNF-alpha in the I/R group were 22.08 +/- 3.85, 21.92 +/- 5.56 and 30.50 +/- 3.77 pg/mL respectively, which were significantly higher than those of the sham-operated group. The AMR group showed lower serum levels of IL-1beta, IL-8 and TNF-alpha (16.66 +/- 3.02,14.73 +/- 2.75 and 22.48 +/- 3.82 pg/mL, respectively) compared with the I/R group (P < 0.01). The pathologic examination displayed that the lung tissue structure was normal and there was no hyperemia in the sham-operated and the AMR groups. The lung tissue structure of the I/R group was nearly normal but there were hyperemia and more inflammatory cells than the sham-operated and the AMR groups. CONCLUSIONS: Amrinone has protections against lung I/R injury, possibly through its anti-oxidation effects and an inhibition of inflammation factors releasing.

[Eye socket reconstruction with free flap].

OBJECTIVE: To discuss the effect of eye reconstruction with free flap. METHODS: Free flap was used in 21 patients of contracted eye socket and anophthalmos. The forearm free flap was utilized in 19 patients,the scapular flap in 2. Free flap with microvascular anastomoses was transferred into contracted eye socket. And hydroxyapatite implant was selectively inserted for intraorbital implantation according to the extent of contracted eye socket postoperation. Eye socket was reconstructed in one stage operation. RESULTS: The flaps were transferred successfully in all patients. All patients were followed up between 4 to 42 months, better cosmetic results were achieved and well-fitted eye prosthesis was weaned. CONCLUSION: Free flap is a useful alternative in treatment of severe contracted eye socket.

[Eye socket reconstruction with free radial forearm flap in anophthalmic orbital syndrome and contracted eye socket].

OBJECTIVE: To assess the effect of eye socket reconstruction with free radial forearm flap. METHODS: Reconstructive procedures were performed in 7 patients underwent orbital exenteration for malignant tumors and in 9 patients underwent enucleation and postoperative irradiation of the orbit for the treatment of retinoblastoma. These patients were suffered from anophthalmic orbital syndrome and contractive eye socket. A microvascular surgical technique with a free radial forearm flap was adopted. Hydroxyapatite implant was inserted as an intraorbital implantation. RESULTS: All patients were followed up for 6 months to 5 years and good cosmetic results were obtained. A large eye socket was achieved permanently. Artificial eye could be fitted with satisfactory results. CONCLUSION: Free radial forearm flap transplantation offers a useful option for the treatment of anophthalmic orbital syndrome.