Comparative investigation of transport and deposition of nebulized particles in nasal airways following various middle turbinectomy.

BACKGROUND: Topical intranasal medication is required following functional endoscopic sinus surgery (FESS). The optimal particle size of transnasal nebulization aimed at the sinonasal cavities is not conclusive. The current study aims to evaluate the effect of particle size and various surgery scope of middle turbinectomy (MT) on post-full FESS drug delivery to the sinonasal cavities. METHODS: Sinonasal reconstructions were performed from post-full FESS CT scans in 6 chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Four additional models representing alternative surgery scopes of MT were established from each post-FESS reconstruction for simulation data comparison. Airflow and particle deposition of nebulized delivery were simulated via computational fluid dynamics (CFD) and validated through in vitro experiments. The optimal particle sizes reaching a deposition of at least 75% of the maximum in the targeted regions were identified. RESULTS: The drug deposition rate onto the targeted regions increased following MT, with the greatest deposition following posterior MT (P-MT). Droplets in the range of 18-26 λm reached a deposition of larger than 75% of the maximum onto the targeted regions. Drug delivery rate in the sinonasal cavities varied significantly among individuals and across different types of MT with varying surgical scopes. CONCLUSIONS: This study is the first to investigate the effect of various surgery scope on drug delivery by transnasal nebulization to the sinonasal cavities. The findings strongly affirm the vast potential of transnasal nebulization as an effective post-FESS treatment option. Moreover, it emphasizes that the drug delivery process via atomizers to the nasal cavity and paranasal sinuses is highly sensitive to the particle size.

Phenotype and genetic characteristics in 20 Chinese patients with 46,XY disorders of sex development.

PURPOSE: 46,XY disorders of sex development (DSD) is the most complicated and common type of DSD. To date, more than 30 genes have been identified associated with 46,XY DSD. However, the mutation spectrum of 46,XY DSD is incomplete owing to the high genetic and clinical heterogeneity. This study aims to provide clinical and mutational characteristics of 18 Chinese patients with 46,XY DSD. METHODS: A total of 20 unrelated individuals with 46,XY DSD were recruited. Whole-exome sequencing (WES) or custom-panel sequencing combined Sanger sequencing were performed to detect the pathogenic mutations. The pathogenicity of the variant was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidance and technical standards recommended by the ACMG and the Clinical Genome Resource (ClinGen). RESULTS: Six patients harbored NR5A1 mutations; two patients harbored NR0B1 mutations; six patients harbored SRD5A2 mutations; six patients harbored AR mutations. Six novel genetic variants were identified involved in three genes (NR5A1, NR0B1, and AR). CONCLUSION: We determined the genetic etiology for all enrolled patients. Our study expanded the mutation spectrum of 46,XY DSD and provided diagnostic evidence for patients with the same mutation in the future.

The association between dietary selenium intake and Hashimoto's thyroiditis among US adults: National Health and Nutrition Examination Survey (NHANES), 2007-2012.

BACKGROUND: Selenium has been shown to influence the pathological processes and physiological functions of thyroid. Although growing evidence has shown that selenium can improve the treatment of Hashimoto's thyroiditis (HT), there is a need to evaluate the association between dietary selenium intake and HT in a large cross-sectional study. This study explored the association between dietary selenium intake and HT based on the National Health reand Nutrition Examination Survey (NHANES) database (2007-2012). METHODS: A total of 8756 of 30,442 participants were included in the study. Dietary selenium intake was the independent variable, while HT was the dependent variable. In addition, the relative importance of the selected variables was determined using the XGBoost model. A smooth curve was constructed based on the fully adjusted model to investigate the potential linear relationship between dietary selenium intake and HT. Smooth curves were also constructed to explore the linear/non-linear relationship between dietary selenium intake and thyroid peroxidase antibody (TPOAb)/ thyroglobulin antibody (TgAb). RESULTS: The mean age of the enrolled participants was 44.35 years (± 20.92). The risk of HT was significantly reduced by a 35% per-unit increase in dietary selenium intake after fully adjusting for covariates according to the model (log2-transformed data; OR 0.65; 95% CI 0.51, 0.83). The XGBoost model revealed that dietary selenium intake was the most important variable associated with Hashimoto's thyroiditis. Dietary selenium intake (Log2-transformed) was negatively correlated with TPOAb levels [- 16.42 (- 22.18, - 10.65), P < 0.0001], while a non-linear relationship was observed between dietary selenium intake and TgAb with an inflection point of 6.58 (95.67 µg, Log2-transformed). CONCLUSION: Dietary selenium intake is independently and inversely associated with HT risk. Moreover, dietary selenium intake is negatively correlated with TPOAb levels and non-linearly correlated with TGAb levels. Therefore, dietary selenium intake may be a safe and low-cost alternative for the prevention and treatment of HT.

Extracellular vesicles-Mediators of opioid use disorder?

Opioid use disorder (OUD) is a growing health emergency in the United States leading to an epidemic of overdose deaths. OUD is recognized as an addictive brain disorder resulting in psychological, cognitive and behavioural dysfunction. These observed clinical dysfunctions are a result of cellular changes that occur in the brain. Derangements in inflammation, neurogenesis and synaptic plasticity are observed in the brains of OUD patients. The mechanisms of these derangements are unclear; however, extracellular vesicles (EVs), membrane bound particles containing protein, nucleotides and lipids are currently being investigated as agents that invoke these cellular changes. The primary function of EVs is to facilitate intercellular communication by transfer of cargo (protein, nucleotides and lipids) between cells; however, changes in this cargo have been observed in models of OUD suggesting that EVs may be agents promoting the observed cellular derangements. This review summarizes evidence that altered cargo of EVs, specifically protein and miRNA, in models of OUD promote impairments in neurons, astrocytes and microglial cells. These findings support the premise that opioids alter EVs to detrimentally affect neuro-cellular function resulting in the observed addictive, psychological and neurocognitive deficits in OUD patients.

[Application effects of 3D visualization reconstruction technique in pheochromocytoma/ paraganglioma surgery].

To investigate the value of 3D visualization reconstruction technology in pheochromocytoma/paraganglioma surgery.The clinical data of 87 patients with pheochromocytoma/paraganglioma admitted to the Department of Urology of Peking Union Medical College Hospital between January 2019 and December 2022 were retrospectively analyzed, and 3D visualization model reconstruction was performed preoperatively in 47 patients [Group A:males was 24 cases,the age M(Q1, Q3)42.00(30.00, 54.00)]. while the remaining 40 patients [Group B: males was 23 cases,the age M(Q1, Q3) 44.00(30.25, 53.75)] was not. The maximum tumor diameter, operation time, intraoperative bleeding, drain retention time and postoperative hospital stay were compared between the two groups. Surgery was successfully completed in both groups. 37 (78.7%) patients in group A underwent laparoscopic surgery, 7 (14.9%) patients underwent open surgery, and 3 (6.4%) patients underwent laparoscopic-to-open surgery. Thirty-one (77.5%) patients in group B underwent laparoscopic surgery, 5 (12.5%) patients underwent open surgery, and 4 (10.0%) patients underwent laparoscopic to open surgery. There was a difference in the maximum diameter of the tumor between the two groups [(6.09±3.02) cm vs (5.32±1.76) cm, P<0.05], the retention time of the drainage tube was significantly shorter in group A compared with group B [(3.20±1.38) d vs (4.02±1.98) d, P<0.05], and the length of the hospital stay after surgery was significantly shorter [(5.75±2.12) d vs (6.49±3.37) d, P<0.05]. Comparison of operation time and intraoperative bleeding between the two groups showed no statistically significant difference (P>0.05).Two cases of postoperative anemia and one case of pulmonary atelectasis in group B patients improved before discharge. Conclusion when the tumor diameter is>6 cm or has a close relationship with the surrounding organs and blood vessels, the use of 3D visual reconstruction technology can formulate and implement a more accurate and safe surgical plan, shorten the retention time of the drainage tube and postoperative hospitalization time, which is conducive to the patient's postoperative recovery and reduce postoperative complications.

[Efficacy of Hintermann calcaneal lengthening osteotomy for flexible flatfoot].

Objective: To investigate the clinical efficacy of Hintermann osteotomy (H-LCL) for flexible flatfoot. Methods: A follow-up study. Clinical data of 30 patients with flexible flatfoot treated with H-LCL operation from January 2020 to December 2021 in Sports Medical Center of the First Affiliated Hospital of Army Medical University were retrospectively analyzed. There were 8 males and 22 females, with a mean age of (39.0±15.2) years. The mean time from symptom onset to the diagnosisï¼»M（Q1，Q3）］was 24.0 (5.5, 102.0) months. The functional and imaging scores of the patients before and after the last follow-up were compared to evaluate the clinical efficacy of the operation. The functional scores included American Orthopedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) of pain, pain interference (PI) and physical function (PF) index in Patient-Reported Outcomes Measurement Information System (PROMIS). And the imaging scores included Meary's angle, calcaneal pitch angle, calcaneal valgus angle and talonavicular coverage angle. Results: The mean operation time was (82.3±24.4) min, and the follow-up periods was (17.9±6.9) months. At the last follow-up, VAS of pain [M(Q1, Q3)] decreased from 5 (4, 6) to 2 (1, 2); PI decreased from 59.8±5.0 to 44.6±5.7; AOFAS increased from 65.2±10.0 to 85.8±3.3; PF increased from 50 (48.5,51.0) to 58.5 (54.0, 66.0); Meary's angle (antero-posterior image) decreased from 15.7° (10.1°, 29.2°) to 3.9° (2.6°, 5.3°); Meary's angle (lateral image) decreased from 13.5°±6.8° to 4.4°±2.6°; calcaneal pitch angle increased from 14.0°±3.3° to 18.6°±4.2°; calcaneal valgus angle decreased from 12.6°±7.3° to 4.3°±2.5°; and talonavicular coverage angle decreased from 20.9°±10.7° to 7.7°±5.2°. The up-mentioned parameters were all improved statistically significant at the last follow-up when compared with those before the operation (all P<0.05). Conclusion: H-LCL brings a significant improvement of clinical outcome scores and good radiological correction of flatfoot deformities in correcting flexible flatfoot, it conforms to the anatomical characteristics of the subtalar joint.

[Observation of visual quality after implantation of a rotational asymmetric refractive intraocular lens with a low addition region using the micromonovision design].

Objective: To investigate the effects of the application of a low addition refractive multifocal intraocular lens (IOL) using the micromonovision design in the non-dominant eye with different degrees of preset myopia on the visual acuity, visual function and visual quality after bilateral cataract surgery. Methods: In this randomized controlled trial, patients who were proposed to undergo bilateral phacoemulsification combined with rotational asymmetric refractive IOL (MF15 IOL) implantation at the First Affiliated Hospital of Zhengzhou University between September 2020 and August 2022 were included. All patients were divided into three groups using the random number method. The target refraction of the IOL in the dominant eye was 0.00 D. Non-dominant eyes were given different preoperative IOL reserve refractions, with the reserved near additional degree>0.20 D and≤0.40 D as the low addition,>0.40 D and≤0.60 D as the medium addition, and>0.60 D and≤0.80 D as the high addition. We compared uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA) and uncorrected near visual acuity (UNVA) of monocular and binocular eyes at 1 day, 1 month and 3 months postoperatively in the 3 groups of patients. Furthermore, the contrast sensitivity, stereopsis, defocus curves and visual quality questionnaire results of binocular eyes were compared at 3 months postoperatively. The statistical methods mainly used were chi-square test, two-factor repeated measures ANOVA, one-way ANOVA, LSD test, Kruskal-Wallis test, and paired t-test. Results: A total of 110 patients (220 eyes) were enrolled in the study, including 48 males and 62 females, with an average age of (59.74±9.38) years. There were 40 patients (80 eyes) in the low additional degree group, 37 patients (74 eyes) in the medium additional degree group, and 33 patients (66 eyes) in the high additional degree group. The differences in distance, intermediate and near visual acuity of the dominant eyes among the three groups were not statistically significant at different measurement timepoints postoperatively (P>0.05). The differences in intermediate and near visual acuity of the non-dominant eyes were also not statistically significant (P>0.05) among the three groups. In contrast, at 3 months, the UDVA of the non-dominant eyes in the low additional degree group (0.04±0.06) and medium additional degree group (0.04±0.07) was significantly higher than that in the high additional degree group (0.08±0.09) (F=4.776, P=0.011, bias η2=0.086). There was no statistically significant difference in binocular uncorrected distance, intermediate and near visual acuity among the three groups at different postoperative timepoints (P>0.05). The binocular UDVA, UIVA and UNVA (logMAR visual acuity) at 3 months postoperatively were -0.04±0.04, 0.03±0.08, 0.10±0.13 in the low addition group, -0.01±0.05, -0.02±0.06, 0.09±0.10 in the medium addition group, and 0.02±0.07, 0.01±0.09, 0.16±0.11 in the high addition group. At 3 months postoperatively, the binocular contrast sensitivity of the low additional degree group was significantly higher than that of the high additional degree group (P<0.05), except that there was no significant difference at the spatial frequency of 6 cycles per degree in the absence of glare (P>0.05). The binocular contrast sensitivity of the medium additional degree group was significantly higher than that of the high additional degree group at the spatial frequencies of 6 and 18 cycles per degree in the glare condition (P<0.05). The difference in the binocular contrast sensitivity between the low and medium additional degree groups did not reach statistical significance (P>0.05). The peak of the binocular defocus curve in the three groups was significantly wider than that in the monocular eyes, and the decline trend was more gentle, with no trough in the middle, and the visual acuity could be maintained above 0.2 (logMAR visual acuity) in the 0.00 D to -3.00 D defocus range. There was no significant difference in the postoperative near stereopsis results among the three groups (P>0.05), with the percentage of near stereopsis sharpness≤60″ reaching 90.00% (36/40), 89.19% (33/37) and 78.79% (26/33), respectively. The proportions of VF-14 scores≥90 in the postoperative questionnaire were 90% (36/40), 91.89% (34/37) and 81.82% (27/33) for the low, medium and high additional degree groups, respectively. The differences in the probability of photic phenomena and spectacles-independent rate were not statistically significant (P>0.05). Conclusion: The use of micromonovision design for bilateral implantation of a rotational asymmetric refractive MF15 IOL, with the non-dominant eye reserved for different near additional degrees, can enable cataract patients to have significantly improved binocular full-range vision, visual function and visual quality. When the degree of reserved near additions in the non-dominant eye preoperatively is>0.20 D and≤0.60 D, it can ensure sufficient binocular UDVA, UIVA and UNVA after surgery, and meanwhile help to obtain superior contrast sensitivity and stereopsis, as well as a satisfactory spectacles-independent rate and low incidence of photic phenomena.

[Clinical observation of spontaneous brain activity in children with congenital cortical cataract amblyopia].

Objective: To investigate the characteristics of spontaneous brain activity in children with congenital cortical cataract amblyopia. Methods: A cross-sectional study was conducted. Twenty cases of unilateral congenital cortical cataract amblyopia (unilateral amblyopia group) and 14 cases of bilateral congenital cortical cataract amblyopia (bilateral amblyopia group) were enrolled from January 2022 to December 2022 at the First Affiliated Hospital of Zhengzhou University. Seventeen age and gender matched children with normal visual acuity were recruited as the healthy control group. Resting-state functional MRI (fMRI) was performed on all participants, and the amplitude of low-frequency fluctuations (ALFF) technique was used to analyze their spontaneous brain activities. The original ALFF value of each voxel was divided by the average ALFF value of the whole brain to obtain the standardized ALFF value (referred to as ALFF value), which reflected the intensity of spontaneous brain activity in different brain regions. General demographic data were compared using one-way analysis of variance, Kruskal-Wallis test, and chi-square test. Comparison of ALFF values was conducted using one-way analysis of variance. Results: There were no significant differences in age, gender, distribution of amblyopic eye or non-dominant eye, and degree of refractive error among the three groups (all P>0.05). Compared to the healthy control group, the unilateral amblyopia group showed higher ALFF values in the right posterior lobe of the cerebellum (67 voxels, t=3.48) and left posterior lobe of the cerebellum (71 voxels, t=4.09), and lower ALFF values in the right postcentral gyrus (91 voxels, t=-3.91), right inferior parietal lobule (73 voxels, t=-4.88), right inferior frontal gyrus (78 voxels, t=-4.09), left inferior parietal lobule (556 voxels, t=-4.82), and left inferior frontal gyrus (122 voxels, t=-4.27) (all P<0.01). The bilateral amblyopia group showed higher ALFF values in the right insula (60 voxels, t=3.54), right Rolandic operculum (69 voxels, t=3.73), right posterior lobe of the cerebellum (54 voxels, t=3.43), and left posterior lobe of the cerebellum (143 voxels, t=3.69), and lower ALFF values in the left inferior frontal gyrus (99 voxels, t=-4.39), left postcentral gyrus (231 voxels, t=-4.28), and right inferior parietal lobule (54 voxels, t=-3.77) (all P<0.01). Compared to the unilateral amblyopia group, the bilateral amblyopia group showed higher ALFF values in the left middle frontal gyrus (52 voxels, t=3.15, P=0.029), left posterior lobe of the cerebellum (77 voxels, t=3.39, P=0.001), and right Rolandic operculum (53 voxels, t=3.59, P=0.007). Conclusion: Children with congenital cortical cataract amblyopia exhibit altered spontaneous brain activity in multiple brain regions, and there are differences in spontaneous brain activity changes between unilateral and bilateral amblyopia.

[Pathological classification of malignant peritoneal mesothelioma and comparative analysis with peritoneal carcinomatosis].

Objective: To analyze the pathological classification of malignant peritoneal mesothelioma (MPeM) and screen the immunohistochemical markers that can distinguish MPeM from peritoneal metastatic carcinoma (PC) . Methods: In June 2020, the pathological results of peritoneal biopsy of 158 MPeM and 138 PC patients from Cangzhou Central Hospital, Cangzhou People's Hospital, and Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2011 to July 2019 were retrospectively analyzed, and the pathological classifications of MPeM in Cangzhou were summarized. Immunohistochemical markers of MPeM and PC patients were analyzed, and receiver operating characteristic curve (ROC curve) was drawn for differential diagnosis of MPeM and PC. Results: There were 55 male and 103 female MPeM patients in Cangzhou, with an average age of 57.1 years old. The asbestos exposure rate was 91.14% (144/158). The most common pathological classifications were cutaneous type, accounting for 90.51% (143/158). There were significant differences in the expression of calreticulum protein, CK5/6, vimentin, D2-40, carcinoembryonic antigen (CEA) and tail type homologous nuclear gene transcription factor 2 (CDX-2) between MPeM and PC (P<0.05). Among the 6 positive markers, the sensitivity of calreticulum protein was the highest (0.905) and CEA was the lowest (0.428) . Conclusion: Calreticulum protein, CK5/6, vimentin, D2-40, CEA and CDX-2 may be used as specific markers to distinguish the diagnosis of MPeM from PC.

[Correlation analysis and benchmark dose study on bone metabolic biochemical index of low doses of exposed hydrogen fluoride workers].

Objective: To analyze correlation of occupational hydrogen fluoride exposure to low doses of bone metabolism index through occupational epidemiological investigation and benchmark dose calculation. Methods: In May 2021, using cluster sampling method, 237 workers exposed to hydrogen fluoride in a company were selected as the contact group, and 83 workers not exposed to hydrogen fluoride in an electronics production company were selected as the control group. The external exposure dose and urinary fluoride concentration, blood and urine biochemical indicators of the workers was measured.The relationship between external dose and internal dose of hydrogen fluoride was analyzed. The external dose, urinary fluoride was used as exposure biomarkers, while serum osteocalcin (BGP), serum alkaline phosphatase (AKP) and urinary hydroxyproline (HYP) were used as effect biomarkers for bone metabolism of hydrogen fluoride exposure. The benchmark dose calculation software (BMDS1.3.2) was used to calculate benchmark dose (BMD) . Results: Urine fluoride concentration in the contact group was correlated with creatinine-adjusted urine fluoride concentration (r=0.69, P=0.001). There was no significant correlation between the external dose of hydrogen fluoride and urine fluoride in the contact group (r=0.03, P=0.132). The concentrations of urine fluoride in the contact group and the control group were (0.81±0.61) and (0.45±0.14) mg/L, respectively, and the difference between the two groups was statistically significant (t=5.01, P=0.025). Using BGP, AKP and HYP as effect indexes, the urinary BMDL-05 values were 1.28, 1.47 and 1.08 mg/L, respectively. Conclusion: Urinary fluoride can sensitively reflect the changes in the effect indexes of biochemical indexes of bone metabolism. BGP and HYP can be used as early sensitive effect indexes of occupational hydrogen fluoride exposure.

[Analysis of the effectiveness of coracoid osteotomy and concentric coaxial reconstruction of the glenoid cavity in the treatment of recurrent anterior dislocation of the shoulder joint].

Objective: To investigate the clinical efficacy of the modified Latarjet procedure in the treatment of recurrent anterior subluxation of the shoulder by "coaxial co-arc" reconstruction of the glenoid cavity. Methods: The clinical data of 103 cases (106 shoulders) of recurrent anterior dislocation of the shoulder admitted to the First Affiliated Hospital of the Army Military Medical University from January 2005 to December 2020 were retrospectively studied. Out of these cases, 84 were males and 19 were females; 31 with left-sided injuries while 75 with right-sided injuries, with a mean age of (29.4±11.5) years (16-61 years). The preoperative anterior fear test was positive, and a modified Latarjet procedure was used to reconstruct the shoulder glenoid defect through a "coaxial co-arc". The Rowe score, simple shoulder test (SST) score, and Visual analogue scale (VAS) score of pain were used to assess the shoulder's function. Parameters such as the postoperative shoulder recurrent dislocation rate, shoulder body external rotation angle, and subscapularis muscle strength changes were recorded postoperatively. Moreover, radiographs and CT scans were used to check for the incidence of osteoarthritis (Samson-Prieto score). Results: After a mean follow-up of 9.0 years (1 to 16 years), bony healing occurred 3 to 6 months postoperatively. The Rowe score improved from 40.4±6.5 preoperatively to 93.2±2.5 (P<0.001), the SST score improved from 5.2±1.3 preoperatively to 10.1±1.5 (P<0.001), and the VAS pain score decreased from 3.5±1.9 preoperatively to 1.1±1.2 (P<0.001) at the final follow-up. The angle of lateral external rotation of the shoulder joint was 58.8°±15.6° preoperatively and 57.6°±14.5° postoperatively with no statistically significant difference (P>0.05). There was no statistically significant difference in the measurement of subscapularis muscle strength between the healthy side and the affected side (P>0.05). In 89.6% of patients after surgery, coaxial co-arc reconstruction of the shoulder glenoid was obtained, and the shoulder glenoid defect and postoperative inclusion angle were significantly improved compared with those before surgery (P<0.001). Postoperatively, new-onset osteoarthritis developed in 7 cases (7/98), arthritis progressed in 2 cases (2/8), incisional healing was poor in 2 cases (2/98), and revision surgery was performed in 2 cases (2/98) due to bone mass detachment. Conclusion: Coracoid osteotomy and concentric coaxial reconstruction of the glenoid cavity elicits adequate good clinical efficacy for cases of recurrent anterior shoulder dislocation, with low recurrence rates, low revision rates and low incidence of osteoarthritis.

[Arthroscopic treatment through Tang's approach in the treatment of posterior talus impingement syndrome].

Objective: To analyze the efficacy of arthroscopic posterior ankle debridement through Tang's approach for the treatment of impingement of posterior tubercle of the talus. Methods: A retrospective analysis was performed on 64 patients (35 males and 29 females) with posterior tubercle impingement of the talus who underwent surgical treatment from September 2011 to May 2019 in First Affiliated Hospital of Military Medical University of the Army. The disease occurred in left foot in 31 cases and in right foot in 33 cases, with an age ranged from 15 to 65 years ((36±7) years). All patients underwent arthroscopic debridement of the posterior tubercle of the talus through Tang's approach, in which the patients were placed in the lateral decubitus position, and the arthroscopic access was constructed via the lateral malleolus apex approach and the posterolateral Achilles tendon approach. All patients were assessed preoperatively and postoperatively with the American Association of Ankle Surgeries (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) for pain, as well as imaging, and the data were compared before and after the operation. Results: All patients were followed-up effectively for (15.6±4.2) months. The preoperative AOFAS ankle-hind foot function score was (84±11) points, and it was (92±9) points at the last follow-up (P<0.05); the VAS score for preoperative pain was (4.5±3.0) points and it was (1.0±0.3) points at the last follow-up (P<0.05). The distance from the preoperative posterior tubercle of the talus to the perpendicular to the tangent line in the imaging evaluation was (4.0±2.0) mm, the vertical distance between the posterior edge of calcaneal joint surface and tangent line was (-8.4±4.2) mm, and the average vertical distance between posterior tubercle of talus and tangent line was (-7.9±4.6) mm after operation, the exposed distance from the lower joint was (-2.1±3.0) mm after operation. Conclusions: Arthroscopic debridement of the posterior tubercle of talus through Tang's approach can effectively alleviate the symptoms caused by the posterior tubercle of talus. Tang's approach has the advantages of avoiding repeated position change and disinfection, and reducing the possibility of infection.

[Visual quality after implantation of a rotational asymmetric refractive intraocular lens in patients with high myopia and cataract].

Objective: To evaluate the visual quality after phacoemulsification and implantation of a rotational asymmetric refractive intraocular lens in patients with high myopia and cataract. Methods: A retrospective cohort study. Sixty-two patients (92 eyes) of the First Affiliated Hospital of Zhengzhou University from June 2017 to December 2019 were evaluated after phacoemulsification and implantation of a rotational asymmetric refractive intraocular lens (LS-313 MF30). According to the axial length, the participants were allocated to either a control group or a high myopia group. Among the 33 patients (46 eyes) in the control group, the axial length was shorter than 26 mm; among the 29 patients (46 eyes) in the high myopia group, the axial length was more than 26 mm. The high myopia group was further divided into two subgroups. The super high myopia subgroup included 12 patients (18 eyes), and the axial length was ≥30 mm; the high myopia subgroup consisted of 17 patients (28 eyes), and the axial length was<30 mm and ≥26 mm. Uncorrected distance visual acuity, uncorrected intermediate visual acuity and uncorrected near visual acuity were recorded after surgery. The follow-up time was more than 6 months. At the end of the follow-up, patients' contrast sensitivity (CS), reading acuity, reading speed and visual quality questionnaire results were assessed. The main statistical methods were two-way repeated measures analysis of variance, independent sample t-test, one-way analysis of variance and Kruskal-Wallis test. Results: There were no significant differences in gender distribution, age, or follow-up time between the control and high myopia groups, the control and high myopia subgroup, or the super high myopia subgroup (all P>0.05). At the end of the follow-up, the uncorrected distance, intermediate and near visual acuity of the super high myopia subgroup was 0.07±0.11, 0.34±0.08 and 0.20±0.09, respectively. The difference in postoperative visual acuity was not statistically significant (all P>0.05). The CS and CS with glare of the high myopia group (3 cpd: 1.48±0.18, 1.42±0.16; 6 cpd: 1.75±0.18, 1.76±0.15; 12 cpd: 1.44±0.24, 1.43±0.19; 18 cpd: 0.90±0.23, 0.85±0.20) were significantly different from the control group (3 cpd: 1.66±0.18, 1.62±0.16; 6 cpd: 1.88±0.14, 1.85±0.11; 12 cpd: 1.54±0.18, 1.53±0.14; 18 cpd: 1.06±0.18, 1.01±0.15) (P<0.05), except at 12 cpd (P=0.05). The CS and CS with glare of the super high myopia subgroup (3 cpd: 1.39±0.21, 1.31±0.13; 6 cpd: 1.66±0.16, 1.64±0.12; 12 cpd: 1.32±0.23, 1.31±0.18; 18 cpd: 0.75±0.16, 0.73±0.15) were worst (all P<0.05). A significant difference between the high myopia subgroup and the control group was only found at 3 cpd (1.53±0.13 vs. 1.66±0.18, 1.50±0.13 vs. 1.62±0.16; both P<0.05). The reading acuity and reading speed of the super high myopia subgroup were lower than the high myopia subgroup and the control group, while the differences were not statistically significant (all P>0.05). The questionnaire survey showed that there was no significant difference in the proportion of glare and halo between the two subgroups and the control group (both P>0.05). No patients reported dissatisfaction. The rate of glasses independents was 11/12 in the super high myopia subgroup, 15/17 in the high myopia subgroup and 31/33 in the control group, with no significant difference (P>0.05). Conclusions: The rotational asymmetric refractive intraocular lens is suitable for patients with high myopia and cataract, and has good far and near vision after operation. However, it could result in relatively low CS for super high myopia patients, so rigorous preoperative examination must be done. (Chin J Ophthalmol, 2021, 57: 358-365).

Influence of family history on risk of second primary cancers and survival in patients with squamous cell skin cancer.

BACKGROUND: Patients with squamous cell skin cancer (SCC) have an excellent prognosis but second primary cancers (SPCs) weaken survival prospects. Family history is a known risk factor for cancer but whether it is a risk factor for SPC in patients with SCC is not known. OBJECTIVES: To quantify the risk of family history on SPCs in patients with SCC and estimate survival probabilities of patients with SPCs depending on family history. METHODS: With 13 945 histologically verified SCCs, relative risks (RRs) were estimated for family history using a generalized regression model. For survival analysis, hazard ratios (HRs) were assessed using a multivariable Cox proportional-hazards model. RESULTS: Family history of invasive SCC increased risk of second invasive SCC [RR = 42·92, 95% confidence interval (CI) 33·69-50·32] compared with risk without family history (RR 19·12, 95% CI 17·88-21·08). Family history of any nonskin cancer in invasive SCC increased risk of the same cancers to be diagnosed as SPC (RRFH = 1·48, 95% CI 1·35-1·61 vs. RRno FH = 1·40, 95% CI 1·32-1·48); significant increases were observed for seven different nonskin cancers. Most results were replicated for in situ SCC. SPC was deleterious for survival irrespective of family history; HR for patients with SPC was 4·28 (95% CI 3·83-4·72) vs. those without SPC (1·04). CONCLUSIONS: Family history of nonskin cancer was associated with approximately a doubling of risk for SPCs in patients with SCC. SPC increases the death rate in patients with SCC 3-4 times, irrespective of family history. Taking family history into account at SCC diagnosis may help prevention or early detection of SPCs. What's already known about this topic? Second primary cancers (SPCs) are frequently diagnosed in patients with invasive and in situ squamous cell carcinoma (SCC); some epidemiological studies suggest a link to immune dysfunction. Family history of cancer is a risk factor for practically all first primary cancers but whether it also influences risk of SPCs in patients with SCC is not known. The possible influence of family history on survival in patients with SCC remains to be established. Linked Comment: Youlden and Baade. Br J Dermatol 2020; 183:414-415.

[Prognostic value of new TNM staging and serum CA125 in malignant peritoneal mesothelioma].

Objective: To explore the relationship between the new Tumor-Node-Metastasis (TNM) staging system and the serum CA125 level with the prognosis of malignant peritoneal mesothelioma (MPeM) . Methods: The clinical data of 74 patients with MPeM diagnosed by pathology and immunohistochemistry were collected from January 2005 to June 2016 in Cangzhou Central Hospital. According to the results of CT-peritoneal carcinoma index (PCI) , the tumor load was divided into T1 (PCI 1-10) , T2 (PCI 11-20) , T3 (PCI 21-30) and T4 (PCI 31-39) , combined with lymph node metastasis and extraperitoneal metastasis, a new TNM staging system was established. And serum CA125 level was measured in the same time. The median survival time of patients with MPeM, the effect of the new TNM staging system, and serum CA125 levels on their prognosis were retrospectively analyzed. Results: Among the 74 patients with MPeM, 25 (33.8%) cases were males and 49 (66.2%) cases were females. There were 8 cases with systemic chemotherapy, 8 cases with heated intraperitoneal chemotherapy, and 1 case with combination chemotherapy. 10 cases were T1, 22 cases were T2, 27 cases were T3, 15 cases were T4, 12 cases had lymph node metastasis and 10 cases had distant metastasis. The median survival time of T1, T2, T3 and T4 were 12, 10, 6 and 3 months respectively. There were 38 (77.6%) cases with high serum CA125 in all 49 cases who have been tested for CA125. The median survival time of positive group and negative group were 6 months and 11 months respectively. 68 (91.9%) patients had died by the end of collecting data. The median survival time was 8 months. Univariate analysis showed that there were significant differences in survival time between patients with different CT-PCI stages, serum CA125 levels, and with or without lymph node and extraperitoneal metastasis (P<0.05) . Multivariate analysis showed that CT-PCI was independent risk factors for the prognosis of MPeM (HR=2.203, 95%CI: 1.475-3.289) . Conclusion: The new TNM staging system and serum CA125 are important for the prognosis of patients with MPeM. Early detection, early diagnosis and comprehensive treatment can improve the survival time of patients with MPeM.

Proof of concept: hip joint damage occurs at the zone of femoroacetabular impingement (FAI) in an experimental FAI sheep model.

OBJECTIVE: In ovine hips chondrolabral damage as seen in cam-type femoroacetabular impingement (FAI) can be induced via an intertrochanteric varus osteotomy. However, it is yet to proven whether the observed cartilage damage is caused by a dynamic cam type impingement. Thus we asked, (1) whether actual cartilage damage observed after FAI induction in ovine hips occurs at the predicted, computed zone of FAI; (2) whether the extent of cartilage damage increases with ambulation time in this animal model? DESIGN: In this experimental, controlled, comparative study 20 sheep underwent unilateral FAI induction through an intertrochanteric varus osteotomy. Preoperatively sheep underwent computed tomography to generate three-dimensional models of the osseous pelvis and femur. The models were used to predict impingement zones before and after simulated varus osteotomy using range of motion (ROM) analysis. Sheep were sacrificed after 14-40 weeks of ambulation. At sacrifice cartilage was inspected and (1) location of actual damage and computed impingement zones were compared; (2) Cartilage damage was compared between short- and long ambulation groups. RESULTS: (1) The average location and the extent of peripheral and central cartilage lesions did not differ with the computed impingement zones (all P > 0.05). (2) Grades of central, posterior cartilage damage were more severe in the long-compared to the short ambulation group (2.2 ± 1.8 vs 0.4 ± 0.5; P = 0.030). CONCLUSIONS: In this experimental ovine FAI model the surgical induction of an osseous impingement conflict between the femur and acetabulum causes cartilage damage at the zone of simulated FAI.

Liver kinase B1 suppresses the metastasis and angiogenesis of lung cancer: involvement of the Shh signaling pathway.

Liver kinase B1 (LKB1) is revealed to have a close relationship with cancers. However, the underlying mechanism remains unclear. This study aimed to reveal the mechanism through which LKB1 performed its role in lung cancer. LKB1 shRNA and overexpression plasmid were employed to investigate the role of LKB1 in lung cancer in vitro and in vivo. The involvement of Shh signaling pathway was assessed by western blot. Silence of LKB1 promoted, while overexpression of LKB1 inhibited the migration, invasion and angiogenesis of lung cancer cells. Further study showed that Shh signaling pathway was suppressed by LKB1. Cyclopamine, a Shh signaling pathway inhibitor, reduced the effects of LKB1 silence, indicating that LKB1 inhibits the migration, invasion and angiogenesis through suppressing the Shh signaling pathway. In vivo study also showed that Shh signaling pathway was involved in the modulation of LKB1 on the metastasis and angiogenesis of lung cancer. Our study demonstrates that LKB1 inhibits the metastasis and angiogenesis of lung cancer through suppressing the Shh signaling pathway.

Advancing porphyrin's biomedical utility via supramolecular chemistry.

Porphyrins are organic heterocyclic macrocycles with photophysical properties well-suited for clinical phototherapy and cancer imaging. However, their wider application in the clinical management of disease is barred by poor aqueous solubility, bioavailability, tumour accumulation and skin phototoxicity. These limitations instigated the development of supramolecular platforms that improved porphyrin pharmacokinetics and tumour-homing. The supramolecular formulation of porphyrins also facilitates single agent-mediated deeper tissue photoactivation, extended imaging and theranostic multimodality, and synergistic application of multiple therapies. Supramolecular porphyrin structures can overcome additional limitations of porphyrin-mediated photodynamic therapy (PDT), including low depths of tissue penetration that restrict PDT to superficial lesions, inability to treat hypoxic tumours, and incomplete tumour damage. In this review, we discuss the photophysical properties of porphyrins, and overview the clinically-relevant advantages and challenges arising from their incorporation within supramolecular platforms. Specifically, fundamentals underlying the ability of these platforms to ameliorate passive and active porphyrin delivery to tumours, achieve deeper tissue PDT via red-shifted porphyrin Q-bands, energy transfer and sonodynamic effects, and enable new porphyrin-mediated theranostics and synergistic therapeutic capabilities will be explained and exemplified with seminal and cutting-edge in vivo studies.

Pharmacokinetics of enrofloxacin after oral, intramuscular and bath administration in crucian carp (Carassius auratus gibelio).

The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (Cmax ) of 2.29, 3.24 and 0.36 µg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half-life (T1/2ß ) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration-time curve (AUC) values were 223.46, 162.72 and 14.91 µg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration.

Pharmacokinetics of cefquinome in crucian carp (Carassius auratus gibelio) after oral, intramuscular, intraperitoneal, and bath administration.

The pharmacokinetics (PK) of cefquinome (CEQ) was studied in crucian carp (Carassius auratus gibelio) after single oral, intramuscular (i.m.), and intraperitoneal (i.p.) administration at a dose of 10 mg/kg body weight and following incubation in a 5 mg/L bath for 5 hr at 25°C. The plasma concentration of CEQ was determined using high-performance liquid chromatography (HPLC). PK parameters were calculated based on mean CEQ concentration using WinNonlin 6.1 software. The disposition of CEQ following oral, i.m., or i.p. administration was best described by a two-compartment open model with first-order absorption. After oral, i.m., and i.p. administration, the maximum plasma concentration (Cmax ) values were 1.52, 40.53, and 67.87 µg/ml obtained at 0.25, 0.23, and 0.35 hr, respectively, while the elimination half-life (T1/2ß ) values were 4.68, 7.39, and 6.88 hr, respectively; the area under the concentration-time curve (AUC) values were 8.61, 339.11, and 495.06 µg hr/ml, respectively. No CEQ was detected in the plasma after bath incubation. Therapeutic blood concentrations of CEQ can be achieved in the crucian carp following i.m. and i.p. administration at a dosage of 10 mg/kg once every 2 days.