AIM: To evaluate the safety and efficacy of accelerated corneal cross-linking(A-CXL)with application of isotonic riboflavin under pedicled corneal epithelial flap in the treatment of thin keratoconus(corneal thickness less than 400 μm after epithelial removal).METHODS: Retrospective study. A total of 46 patients(74 eyes)with keratoconus treated in the refractive surgery department of Ineye Hospital of Chengdu University of TCM from September 2017 to December 2020 were enrolled. According to the preoperative thinnest corneal thickness(TCT), the patients were divided into two groups: 16 patients(20 eyes)with TCT ranging from 400 to <450 μm underwent accelerated corneal cross-linking with application of isotonic riboflavin under pedicled corneal epithelial flap, and the surgical method involves creating a pedicled corneal epithelial flap and lifting it, applying isotonic riboflavin eye drops, repositioning the corneal epithelial flap, performing ultraviolet irradiation and then using corettage of corneal epithlial flap after irradiation. Another 30 patients(54 eyes)with TCT ≥450 μm underwent epithelial-off A-CXL surgery. After follow-up for 12 mo, the results of best corrected visual acuity(BCVA), Sirius three-dimensional corneal topography, and corneal endothelial cell density were collected before and after surgery.RESULTS: At 12 months post-surgery, patients in the pedicled corneal epithelial flap group showed no significant difference in Kmax compared with pre-surgery(P>0.005), while patients in the epithelial-off group showed a significant reduction in Kmax compared with pre-surgery(P<0.005). For both groups, there were no significant differences in BCVA(LogMAR), corneal anterior and posterior surface curvatures(K1, K2), and corneal endothelial cell density at 12 mo post-surgery compared with pre-surgery(all P>0.005). The comparisons of the changes in various parameters between 12 mo post-surgery and pre-surgery for both groups showed no significant differences(all P>0.05).CONCLUSION: Accelerated corneal cross-linking with application of isotonic riboflavin under pedicled corneal epithelial flap surgery is safe and feasible for patients with thin keratoconus, achieving similar control of keratoconus progression as epithelial-off A-CXL.

Objective:To observe the effects of electroacupuncture(EA)combined with Western medication on lower-limb motor function and blood circulation in patients with cerebral infarction-induced hemiplegia in the acute stage. Methods:One hundred eligible patients with acute ischemic stroke accompanied by lower-limb motor dysfunction were allocated to an observation group and a control group using the random number table method,with 50 cases in each group.The control group received routine Western medications for treatment,and the observation group received additional EA intervention.After 2-week and 4-week treatments,the improvement of lower-limb motor function was assessed using the Fugl-Meyer assessment scale for lower extremity(FMA-LE),and changes in the peak blood flow velocities of the posterior tibial(PT)and dorsalis pedis(DP)arteries on the affected side were detected using Doppler. Results:Three cases dropped out during the study,so there were 48 cases in the observation group and 49 in the control group collected for statistical analysis.The FMA-LE score and the peak blood flow velocities of PT and DP arteries increased after 2-week and 4-week treatments in both groups compared with the pre-treatment baseline(P<0.05).After 2-week treatments,the FMA-LE score and the peak blood flow velocities of PT and DP arteries showed no significant differences between the two groups(P>0.05).After 4-week treatments,compared with the control group,the FMA-LE score was higher(P<0.05),and the peak blood flow velocities of PT and DP arteries on the affected side were larger in the observation group(P<0.05). Conclusion:EA combined with Western medication can significantly improve the motor function and blood flow velocity of the affected lower limb in patients with acute cerebral infarction accompanied by hemiplegia.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Objective: To investigate clinical outcomes of modified reattachment of superior peroneal retinaculum (SPR) for patients with recurrent peroneal tendon dislocation. Methods: A total of 24 cases with recurrent peroneal tendon dislocation from December 2012 to June 2017 were treated with modified reattachment of SPR. There were 20 males and 4 females. The average age was 24.9±9.3 years (14-48 years). The average BMI was 23.18±3.50 kg/m² (15.8-32.2 kg/m²). A 4-5 cm incision was made along the lateral margin of the fibula and curved distally around the fibular tip in line with the peroneal excursion. The superior peroneal retinaculum, peroneus longus and peroneus brevis were exposed. The periosteum and SPR were stripped from the fibula. The false pouch was formed. Two suture anchors were inserted into the postero-lateral ridge of the lateral malleolus without damaging the cartilaginous ridge, after which the SPR was reattached to the lateral malleolus with the anchored suture. The inner layer of the false pouch was incised, while the outer layer (periosteum) was sutured with the SPR in a pants-over-vest style. The following items, including American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS), rate of return to previous sports level, time to return to sports activity, complication, and patients satisfaction were evaluated preoperatively and at the final follow-up. Results: The average operation duration was 36.1±8.8 min (20-51 min). The blood loss was 1-10 ml, average 4.1±2.7 ml. The follow-up was carried out in 22 cases for mean 33.9±15.7 months (13-61 months). AOFAS score was improved from 77.8±7.8 points to 95.5±4.3 points significantly (t=-11.89, P<0.001). VAS score was reduced from 4.2±2.4 to 0.3±0.8 significantly (t=7.69, P<0.001). Mean duration return to sports activity was 5.0±1.9 months (3-10 months). A total of 20 patients (91%) returned to their previous sports level. Only one patient (5%) was found with limitation of range of motion, while two patients (9%) reported pain at the scar site without recurrence. The satisfaction rate was 91%. Conclusion Clinical outcomes of modified reattachment of SPR for patients with recurrent peroneal tendon dislocation was safe and effective.

OBJECTIVE: To detect mutations of fibrillin-1 (FBN1) gene in two pedigrees affected with Marfan syndrome (MFS). WETHODS: Peripheral blood samples were collected from MFS patients and their healthy family members for extracting genomic DNA. All of the 65 exons of the FBN1 gene were analyzed by next-generation sequencing. PolyPhen-2 and SIFT was used to predict structural and functional changes in FBN1 protein. RESULTS: Patients from both pedigrees presented ocular and skeletal manifestations suggestive of MFS. Two novel heterozygous mutations of the FBN1 gene, including c.1879C>T (p.R627C) in exon 16 and c.2584T>C (p.C862R) in exon 22, were identified. The same mutations were not found among unaffected members. By bioinformatic analysis, the mutations may affect the structure and function of the FBN1 protein. CONCLUSION The c.1879C>T and c.2584T>C mutations of the FBN1 gene probably account for the disease in the two pedigrees, respectively. Identification of the c.2584T>C has enriched the spectrum of FBN1 gene mutations.
DNA Mutational Analysis ; Exons ; Fibrillin-1 ; genetics ; Fibrillins ; Humans ; Marfan Syndrome ; genetics ; Mutation ; Pedigree

Objective: To investigate the psychological distress, and examine the effects of acculturative stress, positive coping, and negative coping and their interaction on psychological distress among international students in China. Methods: Totally 373 international students were surveyed from central China [being in China of (2. 2 ± 1. 7) years, 248 males, and 125 females]. Psychological distress was measured with the short version of Brief Symptom Inventory (BSI-18), acculturative stress was measured with the Acculturative Stress Scale for International Students (ASSIS), and positive coping (PC) and negative coping (NC) were measured with the Cope Inventory (COPE). Results: The average score of BSI-18 was (0. 66 ± 0. 72). The BSI-18 scores were positively correlated with the scores of ASSIS and NC (r = 0. 49, 0. 31, Ps ＜ 0. 001). Multiple regression showed that the scores of ASSIS, NC, and interaction of ASSIS and NC were positively correlated with the BSI-18 scores (β = 0. 43, 0. 19, 0. 26). Conclusion: Acculturative stress and negative coping are important related factors for psychological distress, and for students suffering higher acculturative stress, the effect of negative coping on psychological distress is larger.

OBJECTIVETo detect potential mutations of fibrillin-1 (FBN1) gene in a child with Marfan syndrome (MFS) and explore its molecular pathogenesis.

METHODSThe 66 exons of the FBN1 gene were analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the structural and functional changes at the protein level.

RESULTSA novel heterozygous mutation c.3998 G>A (p.Cys1333Tyr) was found in exon 32 in the child. The same mutation was not found among his unaffected family members and 683 healthy controls. Multiple sequence alignment showed that this novel mutation was located in a highly conserved region of the FBN1 protein across various species and may induce structural change to a functional domain.

CONCLUSIONThe novel c.3998G>A (p.Cys1333Tyr) mutation of the FBN1 gene probably predisposed the MFS in the child. Above finding has enriched the spectrum of FBN1 mutations.

AIM To study the chemical constituents from Polygonum hydropiper L..METHODS The petroleum ether,ethyl acetate and n-butanol fractions of 95％ ethanol extract from P.hydropiper were isolated and purified by silica,Sephadex LH-20 and recrystallization,then the structures of obtained compounds were identified by spectral data.RESULTS Thirteen compounds were isolated and identified as β-sitosterol (1),aniba dimer A (2),succinic acid (3),quercetin (4),gallic acid (5),daucosterol (6),quercetin-3-O-β-D-glucoside (7),kaempferol-3-O-β-D-glucoside (8),quercetin-3-O-β-galactoside (9),kaempferol-3-O-β-galactoside (10),stigmast-4-ene-3β,6a-diol (11),fumaric acid (12),ellagic acid (13).CONCLUSION Compounds 11 and 12 are isolated from genus Polygonum for the first time,compounds 2,8,10 and 13 are first obtained from this plant.

Objective To explore the mediating effect of psychological flexibility in the relationship between the two dimensions of type-D personality(negative affect and social inhibition)and pathological in-ternet use.Methods 592 university students were sampled from central China district and were adminis-tered with Adolescent Pathological Internet Use Scale(APIUS),Type-D personality scale(DS14)and Ac-ceptance and Action Questionnaire-Second Edition(AAQ-Ⅱ).Results Pathological internet use(2.56 ± 0.61)positively correlated with negative affect(1.58±0.78)and social inhibition(1.96±0.61)(r=0.37, 0.25)respectively,and negatively correlated with psychological flexibility(4.69±1.15)(r=-0.40).Path a-nalysis with latent variables showed psychological flexibility partially but significantly mediated the predictive effect of negative affect and social inhibition on pathological internet use.The mediation rates were 56% for negative affect and 62% for social inhibition.Conclusion Psychological flexibility has significant incremen-tal validity beyond two dimensions of type-D personality,and partially mediated the effect of negative affect and social inhibition on pathological internet use.These results suggest the intervention focus of PIU can be psychological flexibility.