Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes.

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

TEMPO/O2 Synergistically Mediated BiBrO-Photocatalyzed Decarboxylative Phosphorylation of N-Arylglycines.

With both TEMPO and O2 (in air) as the homogeneous redox mediators, BiBrO as the heterogeneous semiconductor photocatalyst, the first example of semi-heterogeneous photocatalytic decarboxylative phosphorylation of N-arylglycines with diarylphosphine oxides was established. A series of α-amino phosphinoxides were efficiently synthesized.

Phototriggered Self-Catalyzed Phosphorylation of 3,4-Dihydroquinoxalin-2(1H)-ones with Diarylphosphine Oxides in EtOH.

A highly effective external photocatalyst- and additive-free method for the phosphorylation of 3,4-dihydroquinoxalin-2(1H)-ones to produce phosphorylated dihydroquinoxalin-2(1H)-ones has been reported. A wide variety of phosphorylated products were formed in good to excellent yields. Preliminary mechanistic studies reveal that the phosphorylation process involves an EnT process, a SET process, a HAT process, and a deprotonation process.

Balance training benefits chronic ankle instability with generalized joint hypermobility: a prospective cohort study.

BACKGROUND: Balance training is the first choice of treatment for chronic ankle instability (CAI). However, there is a lack of research on the effects of balance training in CAI with generalized joint hypermobility (GJH). This study is to compare the outcomes of balance training in CAI patients with and without GJH. METHODS: Forty CAI patients were assigned into the GJH group (Beighton ≥ 4, 20) and non-GJH group (Beighton < 4, 20) and they received same 3-month supervised balance training. Repeated measure ANOVA and independent t test were used to analyze self-reported questionnaires (Foot and ankle ability measure, FAAM), the number of patients experiencing ankle sprain, isokinetic muscle strength and postural control tests (Star excursion balance test, SEBT and Balance errors system, BES) before training, post-training immediately, and post-training 3 months, respectively. RESULTS: At baseline, no differences were found between groups with except for GJH group having poorer SEBT in the posteromedial direction (83.6 ± 10.1 vs 92.8 ± 12.3, %) and in the posterolateral direction (84.7 ± 11.7 vs 95.7 ± 8.7, %). Following the balance training, GJH group demonstrated lower re-sprain ratio (immediately after training, 11.1% vs 23.5%, 3 month after training, 16.7% vs 29.4%) than non-GJH group, as well as greater FAAM-S score, plantarflexion strength and dorsiflexion strength at post-training immediately and 3 months, and both groups improved similarly in the FAAM-A score, muscle strength and balance control (SEBT in the posterior-lateral and posterior-medial directions, and BES scores) compared with baseline. CONCLUSIONS: CAI patients with GJH gained equally even better postural stability and muscle strength after the balance training than the non-GJH patients. Balance training could still be an effective treatment for CAI patients with GJH before considering surgery. TRIAL REGISTRATION: ChiCTR1900023999, June 21st, 2019.

Both Open and Arthroscopic All-Inside Anatomic Reconstruction With Autologous Gracilis Tendon Restore Ankle Stability in Patients With Chronic Lateral Ankle Instability.

PURPOSE: To compare the return to sports and short-term clinical outcomes between the arthroscopic all-inside and the open anatomic reconstruction with gracilis tendon autograft for chronic lateral ankle instability (CLAI) patients. METHODS: From March 2018 to January 2020, 57 CLAI patients were prospectively included with arthroscopic all-inside anatomic reconstruction (n = 31) or open anatomic reconstruction (n = 26) with gracilis tendon autograft. The patients were evaluated before operation and at 3 months, 6 months, 12 months, and 24 months after surgery. The American Orthopaedic Foot and Ankle Society score (AOFAS), visual analog scale (VAS), and Karlsson-Peterson score were evaluated at each time point, and stress radiography with a Telos device was performed before surgery and at final follow-up. The time to return to full weightbearing walking, jogging, sports, and work, Tegner activity score, and complications were recorded and compared. RESULTS: All the subjective scores significantly improved after surgery from the preoperative level. Compared with the open group, the arthroscopic group demonstrated significantly earlier return to full weightbearing walking (8.9 vs 11.7 weeks, P < .001), jogging (17.9 vs 20.9 weeks, P = .012), and recreational sports (22.4 vs 26.5 weeks, P = .001) with significantly better AOFAS score and Karlsson score at 3 to 6 months, and better VAS score at 6 months after surgery. The 2 groups demonstrated no significant difference in the surgical duration or surgical complications. No significant difference was found in the clinical scores or stress radiographic measurements at 24 months after surgery (P > .05). CONCLUSION: Compared with the open procedure, the arthroscopic all-inside anatomic lateral ankle ligament reconstruction with autologous gracilis tendon could achieve earlier return to full weightbearing, jogging, and recreational sports with less pain and better ankle functional scores at 3 to 6 months after surgery. Similar favorable short-term clinical outcomes were achieved for both techniques at 2 years after surgery. STUDY DESIGN: Level I, randomized controlled trial.

Arthroscopic modified Broström procedure achieved similar favorable short term outcomes to open procedure for chronic lateral ankle instability cases with generalized joint laxity.

PURPOSE: To compare the short-term clinical outcomes of the open versus arthroscopic modified Broström procedure in generalized joint laxity (GJL) patients. METHODS: From January 2018 to January 2020, 64 consecutive patients with chronic lateral ankle instability (CLAI) and GJL (Beighton score ≥ 4) were prospectively enrolled into two groups: those who underwent the open modified Broström procedure (open group, n = 32) and those who underwent the arthroscopic modified Broström procedure (arthroscopic group, n = 32). Patients underwent an open or arthroscopic modified Broström procedure based on the time when they attended the clinic for consultation. All patients were followed-up at 3, 6, 12, and 24 months postoperatively. The clinical outcomes were evaluated using the visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, and Karlsson score, and the radiographic outcomes were assessed using stress radiography at 24 months postoperatively. The time to return to work and the failure rate were also evaluated and compared. RESULTS: Follow-up was completed for 31 patients in the open group and 30 patients in the arthroscopic group. No significant differences were found between the two groups in terms of demographic characteristics, Beighton score (6.2 ± 1.9 vs. 5.5 ± 1.4, n.s.), or duration of symptoms. There were no significant differences in the functional scores before surgery and at 6, 12 and 24 months postoperatively or in the mean anterior translation of the talus and talar tilt angle on stress radiography at 24 months postoperatively between the open and arthroscopic groups. Compared to the open group, the arthroscopic group showed a significantly earlier return to work (6.8 ± 2.1 vs. 8.1 ± 2.4 weeks, p = 0.006). There was no significant difference in terms of the failure rate between the open and arthroscopic groups (16.1% vs. 23.3%, n.s.). CONCLUSION: Arthroscopic modified Broström procedure achieved similar short-term outcomes to the open procedure for GJL patients. Arthroscopic modified Broström procedure showed an earlier return to work than the open modified Broström procedure and was an alternative to open surgery for CLAI patients with GJL. LEVEL OF EVIDENCE: III. CLINICAL TRIAL REGISTRATION: This study is a prospective study NCT05284188.

Anatomic reconstruction using the autologous gracilis tendon achieved less sprain recurrence than the Broström-Gould procedure but delayed recovery in chronic lateral ankle instability.

PURPOSE: To compare the return-to-activity and long-term clinical outcomes between anatomic lateral ligament reconstruction using the autologous gracilis tendon and modified Broström-Gould (MBG) procedure in chronic lateral ankle instability (CLAI). It was hypothesised that there was no difference between the two techniques. METHODS: From 2013 to 2018, 30 CLAI patients with grade III joint instability confirmed by anterior drawer test underwent anatomic reconstruction of lateral ankle ligament with the autologous gracilis tendon (reconstruction group) in our institute. Another 30 patients undergoing MBG procedure (MBG group) were matched in a 1:1 ratio based on demographic parameters. The post-operative American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) pain score, Tegner activity score, Karlsson-Peterson score, surgical complications, return-to-activities and work were retrospectively evaluated and compared between the two groups. RESULTS: All subjective scores significantly improved after the operation (all with p < 0.001) without difference between the two groups (all n.s.). The MBG group showed a significantly higher proportion of postoperative sprain recurrence than the reconstruction group (26.7% vs. 0, p = 0.002). The reconstruction group showed a significantly longer period to start walking with full weight-bearing (10.5 ± 6.9 vs. 7.0 ± 3.1 weeks, p = 0.015), jogging (17.1 ± 8.9 vs. 12.7 ± 6.9 weeks, p = 0.043) and return-to-work (13.5 ± 12.6 vs. 8.0 ± 4.7 weeks, p = 0.039) than the MBG group. CONCLUSIONS: Both anatomic reconstruction using the autologous gracilis tendon and MBG procedure could equally achieved reliable long-term clinical outcomes and the tendon reconstruction showed a relatively lower incidence of postoperative sprain recurrence but delayed recovery to walking, jogging and return-to-work. The MBG procedure was still the first choice with rapid recovery but the tendon reconstruction was recommended for patients with higher strength demand. LEVEL OF EVIDENCE: III.

The L-shaped tunnel technique showed favourable outcomes similar to those of the Y-graft technique in anatomic lateral ankle ligament reconstruction.

PURPOSE: To compare the mid- to long-term clinical and radiological outcomes of the confluent L-shaped tunnel technique with the Y-graft technique for anatomic lateral ankle ligament reconstruction. METHODS: This retrospective study involved 41 patients who underwent lateral ankle ligament reconstruction between 2013 and 2018. Based on the tunnel direction and tendon fixation method at the fibula side, patients were divided into two groups, with 17 patients in the L-shaped tunnel group and 24 patients in the Y-graft group. The American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) pain score, Tegner score, and Karlsson score were evaluated and compared preoperatively and at follow-up. Anterior talar translation and talar tilt at stress radiographs, postoperative sprain recurrence, range of motion (ROM) restriction, sensory disturbance, etc., were also collected and compared. RESULTS: The mean follow-up times were 72 and 42 months for the L-shaped group and Y-graft group, respectively. The median VAS pain score, Tegner score, AOFAS score, Karlsson score significantly improved from a preoperative level in both groups (all with p < 0.01). No significant difference was found between the two groups regarding the changes from preoperatively to postoperatively except for the VAS pain score reduction (1.58 ± 1.58 in the L-shaped group vs. 2.53 ± 1.29 in the Y-graft group, p = 0.035). The incidence of flexion-extension ROM restriction (≥ 5°) was significantly higher in the Y-graft group (41.2%) than in the L-shaped group (12.5%) (p = 0.035). CONCLUSIONS: Both the confluent L-shaped tunnel technique and the Y-graft technique significantly improved symptoms, ankle function, and radiographic outcomes in patients with chronic lateral ankle instability (CLAI) at mid- to long-term follow-up. The confluent L-shaped tunnel technique resulted in lower rates of flexion-extension ROM restriction, while the Y-graft technique showed better VAS pain reduction. This result could provide further evidence for the surgical treatment of CLAI. LEVEL OF EVIDENCE: III.

A High Frequency of Peripheral Blood IL-22(+) CD4(+) T Cells in Patients With New Onset Type 2 Diabetes Mellitus.

BACKGROUND: This study is aimed at investigating the frequency of different functional IL-22(+) CD4(+) T cells in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: The frequency of circulating IFN-γ+IL-17-IL-22-CD4(+) (Th1), IFN-γ-IL-17A+IL-22-CD4(+) (Th17), and IFN-γ-IL-17A-IL-22(+) CD4(+) (Th22), and other subsets of IL-22(+) CD4(+) T cells in 31 patients with new onset T2DM and 16 healthy controls was characterized by flow cytometry. The levels of serum IL-22, IL-17, IFN-γ, insulin C-peptide, hemoglobin A1c (HbA1c), fasting plasma glucose, and insulin were examined. RESULTS: The frequency of Th1, Th17, Th22, IFN-γ(+) IL-17(-) IL-22(+) , and IFN-γ(-) IL-17(+) IL-22(+) CD4(+) T cells and the concentrations of IL-22, but not IL-17 and IFNγ, in the patients were significantly higher than controls. The percentages of Th22 cells were correlated positively with the frequency of IFN-γ(-) IL-17(+) IL-22(+) CD4(+) T cells, the values of body mass index (BMI) and homeostatic model assessment insulin resistance (HOMA-IR), and the levels of serum IL-22 in those patients. CONCLUSION: Our data suggest that IL-22(+) CD4(+) T cells may contribute to the early process of T2DM.

CD4(+)CD25(-)Foxp3(+) T cells play a role in tuberculous hydrothorax rather than malignant hydrothorax.

BACKGROUND: Foxp3(+) T cells regulate inflammation and tumorigenesis. However, little is known about the role of different subsets of Foxp3(+) T cells in malignant or tuberculous hydrothorax. METHODS: The numbers of CD4(+)CD25(+)Foxp3(+), CD4(+)CD25(-)Foxp3(+) T cells and the levels of some inflammatory cytokines in patients with tuberculous hydrothorax, malignant hydrothorax, and healthy controls (HCs) were examined by flow cytometry and ELISA. The potential association between the numbers of different subsets of Foxp3 + T cells and the values of clinical measures were analyzed. RESULTS: The numbers of peripheral blood CD4(+)CD25(+)Foxp3(+) T cells were greater in malignant hydrothorax patients than in HCs, but fewer than those of hydrothorax in patients. The percentages of circulating IL-10(+) or LAP(+) CD4(+)CD25(+)Foxp3(+) T cells were higher than in the hydrothorax in patients with malignant hydrothorax. The numbers of circulating CD4(+)CD25(-)Foxp3(+) T cells were significantly fewer in patients with tuberculous hydrothorax than in HCs, and both the numbers of circulating CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)Foxp3(+) T cells were significantly fewer than in the hydrothorax in patients. Significantly higher percentages of circulating IL-10(+) or LAP(+) CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)Foxp3(+) T cells were detected in tuberculous hydrothorax patients. The numbers of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)Foxp3(+) T cells were associated with hydrothorax adenosine deaminase (ADA) levels in tuberculous hydrothorax patients, while CD4(+)CD25(+)Foxp3(+) T cells were associated with carcino-embryonic antigen (CEA) in malignant hydrothorax patients. The concentrations of serum IL-6 and TGF-ß in the patients were significantly higher than that in the HCs, but lower than that in the corresponding hydrothorax. A similar pattern of IL-10 was observed in different groups, except that there was no significant difference in the levels of serum IL-10 between the tuberculous hydrothorax patients and HCs. CONCLUSIONS: CD4(+)CD25(-)Foxp3(+) T cells, which have lower inhibitory function than CD4(+)CD25(+)Foxp3(+) T cells, may play a role in tuberculous hydrothorax.

The expression of TLR-9, CD86, and CD95 phenotypes in circulating B cells of patients with chronic viral hepatitis B or C before and after antiviral therapy.

AIMS: This study aimed to assess the differential expression of specific B cell subtypes in patients with chronic viral hepatitis. METHODS: The frequencies of differential expression of specific B cell subtypes in patients with chronic viral hepatitis and healthy controls were assessed by flow cytometry using monoclonal antibodies specific for CD38, CD27, CD86, CD95, TLR-9, and IgD. The effect of adefovir treatment on B cell subsets in HBV patients was determined. The values of clinical parameters in the patients were also measured. RESULTS: The frequency of CD86+ B cells was not significantly different in chronic HBV patients but was higher in HCV patients compared with that in healthy controls. CD95 and IgD levels were lower in HBV and HCV patients than in healthy controls. A significant negative correlation occurred between the proportion of CD95+ B cells and HBV DNA viral load. The frequency of TLR-9 on the B cells in HBV and HCV patients was higher compared with that of healthy controls. After treatment with adefovir, the frequency of CD95 and IgD expressed on B cells was increased in HBV patients. CONCLUSIONS: Activated B cells and exhausted B cells homeostasis were commonly disturbed in HBV and HCV patients.

[Effect of anterior cruciate ligament rupture on hamstring: quadriceps ratio during isokinetic knee extension and flexion at 30 degrees of flexion].

OBJECTIVE: To evaluate the change in hamstring (H):quadriceps (Q) ratio following anterior cruciate ligament (ACL) rupture during isokinetic knee extension and flexion at 30 degrees of flexion which is important for knee dynamic function. METHODS: A study was performed in 25 male complete unilateral ACL ruptures. Isokinetic concentric and eccentric quadriceps and hamstring muscle tests in both the deficient knees and intact knees were performed at 60°/s, respectively. At 30 degrees of flexion, the average torque of quadriceps and hamstring, Qe:Qc ratios (ratios of eccentric quadriceps to concentric quadriceps muscle torque), He:Hc ratios (eccentric hamstring to concentric hamstring), Hc:Qc ratios (concentric hamstring to concentric quadriceps), He:Qc ratios (eccentric hamstring to concentric quadriceps), and Hc:Qe ratios (concentric hamstring to eccentric quadriceps) were calculated. Wilcoxon matched-pairs signed-ranks test was used. RESULTS: At 30 degrees of knee flexion, a significant reduction (P<0.05) in the average torque of quadriceps was observed at concentric and eccentric 60°/s produced by the deficient-side compared with the intact side. In addition, Hc:Qc, He:Qc, and Qe:Qc significantly increased on the ACL-deficient side. CONCLUSION: The change in H :Q ratio in the mode of isokinetic 60°/s at 30 degrees of knee flexion might therefore be a new tool to objectively document muscle function in ACL-deficient knee.

Treatment with telbivudine positively regulates antiviral immune profiles in Chinese patients with chronic hepatitis B.

Chronic infection with hepatitis B virus (HBV) is associated with impairment of T and NK cell immunity. This study was aimed at investigating the impact of treatment with telbivudine (LDT) on T and NK cell immunity in patients with chronic hepatitis B (CHB). A total of 54 CHB patients and 30 healthy controls (HC) were recruited. Individual patients were treated orally with 600 mg LDT daily for 13 months. The serum HBV DNA loads, the levels of the HBV-related biomarkers alanine aminotransferase (ALT) and aspartate transaminase (AST), and the numbers of different subsets of peripheral T and NK cells in subjects were measured before and longitudinally after LDT treatment. Following treatment with LDT, the serum HBV DNA loads and the percentages of HBsAg- or HBeAg-seropositive cases were gradually reduced, accompanied by decreased levels of serum ALT and AST. In comparison with the HC, fewer CD3(-) CD56(+) and CD244(+) NK cells and CD3(+) CD8(+) T cells, lower frequencies of cytokine(+) CD4(+) T cells, and more CD3(+) CD4(+), CD4(+) CD25(+) Foxp3(+), CD4(+) CD25(+) CD127(low), and CD8(+) PD-1(+) T cells were detected in CHB patients. Treatment with LDT increased the numbers of NK and CD8(+) cells and the frequencies of cytokine(+) CD4(+) T cells but reduced the numbers of CD4(+) CD25(+) Foxp3(+), CD4(+) CD25(+) CD127(low), and CD8(+) PD-1(+) T cells in CHB patients. The frequencies of cytokine(+) CD4(+) T cells were negatively associated with the levels of serum HBV DNA, ALT, and AST. Thus, treatment with LDT inhibits HBV replication, modulates T and NK cell immunity, and improves liver function in Chinese patients with CHB.

Downregulation and altered function of natural killer cells in hepatitis B virus patients treated with entecavir.

The aim of the present study was to investigate the natural killer (NK) cell phenotype and function in chronic hepatitis B virus (HBV) patients and to study the effects of entecavir therapy (10 mg/day, p.o.) on these responses. Peripheral blood NK cells were collected from 18 chronic HBV patients and 14 healthy controls. The effect of entecavir therapy on the phenotype and function of NK cells in chronic HBV patients was characterized by flow cytometry analysis. Concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), HBV viral loads in both groups and potential associations between the frequency of peripheral NK cell subsets and clinical measures were determined. There was a significant reduction in the number of CD3(-)CD56(+) NK cells in chronic HBV patients compared with healthy controls. Furthermore, there were significant increases in the percentage of CD3(-)CD56(+)NKG2D(+) and CD3(-)CD56(+)NKP30(+) NK activating receptors in chronic HBV patients compared with healthy individuals, who exhibited downregulated expression following entecavir treatment. Spearman's correlation analysis revealed that there was a significant positive correlation between the percentage of NKG2D(+) and NKP30(+) NK cells and serum ALT levels. Characterization of NK cell degranulation indicated that the frequency of CD107a(+) NK cells in HBV patients (in response to K562 stimulation) was significantly greater than in healthy controls but decreased following entecavir treatment. Entecavir treatment of hepatitis B e antigen-positive chronic HBV-infected patients not only led to a reduction in HBV DNA loads and normalization of ALT and AST levels, but also resulted in the recovery of NK cell-mediated immunity.

High frequencies of CD158b+ NK cells are associated with persistent hepatitis C virus infections.

BACKGROUND: During the early phases of a hepatitis C virus (HCV) infection, NK cell activation appears to be critical to the induction of adaptive immune responses that have the potential of clearing the infection. This study aimed to investigate the phenotype and function of NK cells in chronic HCV (CHC) patients, particularly patients who cleared HCV infections spontaneously (SR-HCV). MATERIAL AND METHODS: Peripheral blood NK cells were compared between 36 CHC patients, 12 SR-HCV patients, and 14 healthy controls (HC). The phenotype and function of NK cells were characterized by flow cytometry. In addition, the potential associations between the frequency of NK cell subsets and ALT, AST and HCV viral loads were also analyzed. RESULTS: Our data revealed that the population of CD3-CD56+ NK cells was significantly decreased in CHC and SR-HCV patients compared to levels in HC (P = 0.031, P = 0.014). Interestingly, we found that the levels of the CD158b inhibitory receptor were higher in CHC patients compared to levels observed in HCand SR-HCV subjects (P = 0.018, P = 0.036). In addition, the percentages of the activation receptors NKp30 and NKp46 were significantly decreased in CHC and SR-HCV patients compared to their expression levels in HC (P < 0.05). Moreover, the frequencies of inducible CD107a (but not IFN-γ-secreting) NK cellsfrom both CHC and SR-HCV patients were significantly lower than frequencies observed in controls (P = 0.018, P = 0.027). CONCLUSION: Our data indicated that the higher frequency of inhibitory NK cells combined with fewer activated NK cells may be associated with HCV-related chronic inflammation involved in CHC pathogenesis.

Effect of Arthroscopically Confirmed Syndesmotic Widening on Outcome Following Isolated Broström Operation for Chronic Lateral Ankle Instability.

BACKGROUND: Tibiofibular syndesmosis (TFS) widening sometimes is not evident on radiography but can be found under arthroscopy in chronic lateral ankle instability (CLAI). This study aimed to evaluate the effect of TFS widening severity on clinical outcomes and return to activities after isolated Broström operation in CLAI patients and to propose an indication for its surgical intervention. METHODS: A total of 118 CLAI patients undergoing diagnostic ankle arthroscopy and open Broström-Gould operation were included. Based on the middle width of TFS measured under arthroscopy, patients were divided into the TFS-2 group (≤2 mm, n = 44), the TFS-3 group (2-4 mm, n = 42), and the TFS-4 group (≥4 mm, n = 32). The time to return to recreational sport and work, Tegner activity score, and proportion of returning to preinjury sports at the final follow-up were evaluated and compared. Other subjective evaluations included the American Orthopaedic Foot & Ankle Society score, visual analog scale, and Karlsson-Peterson score. RESULTS: Among the 3 groups, the TFS-4 group demonstrated the longest mean time to return to work and recreational sports, with the lowest proportion returning to preinjury sports. The TFS-4 group showed a significantly higher rate of sprain recurrence (12.5%) than the other 2 groups (P =.021). All the other subjective scores significantly improved after the operation without differences among the 3 groups. CONCLUSION: Concomitant severe syndesmotic widening adversely affects the return to activities after Broström operation in CLAI cases. The CLAI patients with a middle TFS width ≥4 mm were associated with delayed return to work and sports, a lower proportion of returning to preinjury sports, and more sprain recurrence, which might require further surgical intervention for syndesmosis in addition to Broström surgery. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Simultaneous Treatment of Osteochondral Lesion Does Not Affect the Mid- to Long-Term Outcomes of Ligament Repair for Acute Ankle Sprain: A Retrospective Comparative Study with a 3-11-Year Follow-up.

Purpose: This study aims to evaluate the mid- to long-term outcome of concurrent arthroscopic treatment of osteochondral lesion (OCL) and open anatomical repair of lateral ankle ligaments for severe acute ankle sprain patients and compare them to the outcome of those without OCL. Methods: A total of 166 patients with grade III acute lateral ankle ligament injuries underwent concurrent ankle arthroscopy and open anatomic ligament repair. Forty-three patients (group A) with OCL underwent arthroscopic treatment followed by open ligament repair. A total of 105 patients (group B) without OCL were followed up as the control. The evaluation parameters included sports recovery, postoperative visual analog scale (VAS) pain score, American Orthopaedic Foot and Ankle Society (AOFAS) score, Tegner score, sprain recurrence, satisfaction, and range of motion. Patients in group A were then subgroup-analyzed according to age, sex, body mass index, injury side, OCL location, and stage (Ferkel and Cheng's staging system). Results: The postoperative exercise level of the two groups recovered to more than 90% of the normal level (91.2% ± 11.2% in group A and 90.9% ± 13.3% in group B, n.s.). The average time of group A and group B to return to preinjury sports activity was respectively 4.4 ± 1.0 months and 4.4 ± 1.2 months with no significant difference (p = 0.716). No significant differences were found in the preoperation VAS pain score, AOFAS score, and Tegner score between the two groups. The postoperative VAS pain score in group A was significantly higher than that in group B (0.8 ± 1.7 vs. 0.3 ± 0.8, p = 0.027), but the difference was not clinically important. The postoperative VAS pain score of patients with stage D-F lesions was significantly higher than that of patients with stage B-C lesions (1.3 ± 2.1 vs. 0.3 ± 0.9, p = 0.038). Conclusions: For the severe acute ankle sprain combined with OCL, the simultaneous arthroscopic treatment and open lateral ankle ligament repair achieved good mid- to long-term outcomes. Except that the pain was more pronounced than in the control group, there were no differences in other outcomes. Postoperative pain was positively correlated with the grade of OCL.

The effectiveness and sustainability of supervised balance training in chronic ankle instability with grade III ligament injury: a one-year prospective study.

BACKGROUND: To determine the effectiveness and sustainability of supervised balance training in people with chronic ankle instability (CAI) with grade III ligament injury. METHODS: Twenty young adults (12 males and 8 females) diagnosed with CAI with grade III ligament injury underwent 3 months of supervised balance training. The self-reported functional questionnaire, plantar pressure (walking and single leg standing), and isokinetic ankle strength were consecutively evaluated at pre-training, 3 months, 6 months and one year. Paired T tests were used to explore changes in muscle strength and plantar pressures following the supervised balance training. According to whether the patient had sprain recurrence, the patients were divided into sprain recurrence group and control group. The risk factors of sprain recurrence were explored with univariate analysis and multivariable logistic regression. RESULTS: The self-reported functional scores, the plantar pressure distribution and the muscle strength showed significant immediate improvements after 3 months of supervised balance training. At 6 months post-training, peak force under 2nd metatarsal, time to peak force under the medial hindfoot, time to boundary measurements and dorsiflexion, and eversion strength were partly declined to the pre-training level. 16 patients (80%) resumed the daily life and sports without sprain recurrence during the follow-up. Four patients (20%) reported ankle sprain during the follow-up, and the sprain recurrence group showed significantly higher Beighton scores (p = 0.012) and weaker initial inversion strength (p = 0.022) than the control group. CONCLUSIONS: Three months' of supervised balance training could effectively improve postural control and muscle strength of CAI cases with grade III ligament injury, although these improvements would partially deceased over time. Additional strength exercises for dorsiflexion and eversion should be supplemented from 6 months. Higher Beighton score and initial inversion muscle strength weakness might increase the risk of sprain recurrence. TRIAL REGISTRATION: ChiCTR, ChiCTR1900023999, Registered 21 June 2019, https://www.chictr.org.cn/edit.aspx?pid=39984&htm=4.

Non­small cell lung cancer carrying PBRM1 mutation suggests an immunologically cold phenotype leading to immunotherapy failure even with high TMB.

High tumor mutation load (TMB-H, or TMB ≥ 10) has been approved by the U.S. FDA as a biomarker for pembrolizumab treatment of solid tumors, including non­small cell lung cancer (NSCLC). Patients with cancer who have immunotherapy-resistant gene mutations cannot achieve clinical benefits even in TMB-H. In this study, we aimed to identify gene mutations associated with immunotherapy resistance and further informed mechanisms in NSCLC. A combined cohort of 350 immune checkpoint blockade-treated patients from Memorial Sloan Kettering Cancer Center (MSKCC) was used to identify genes whose mutations could negatively influence immunotherapy efficacy. An external NSCLC cohort for which profession-free survival (PFS) data were available was used for independent validation. CIBERSORT algorithms were used to characterize tumor immune infiltrating patterns. Immunogenomic features were analysed in the TCGA NSCLC cohort. We observed that PBRM1 mutations independently and negatively influence immunotherapy efficacy. Survival analysis showed that the overall survival (OS) and PFS of patients with PBRM1 mutations (MT) were significantly shorter than the wild type (WT). Moreover, compared with PBRM1-WT/TMB-H group, OS was worse in the PBRM1-MT/TMB-H group. Notably, in patients with TMB-H/PBRM1-MT, it was equal to that in the low-TMB group. The CIBERSORT algorithm further confirmed that the immune infiltration abundance of CD8+ T cells and activated CD4+ memory T was significantly lower in the MT group. Immunogenomic differences were observed in terms of immune signatures, T-cell receptor repertoire, and immune-related genes between WT and MT groups. Nevertheless, we noticed an inverse relationship, given that MT tumors had a higher TMB than the WT group in MSKCC and TCGA cohort. In conclusion, our study revealed that NSCLC with PBRM1 mutation might be an immunologically cold phenotype and exhibited immunotherapy resistance. NSCLC with PBRM1 mutation might be misclassified as immunoresponsive based on TMB.

Prevalence and etiology of abnormal liver tests in an adult population in Jilin, China.

BACKGROUND: Serum biochemical liver tests (LTs) (alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase) and platelet counts are often used to screen for chronic liver disease. We determined the prevalence and etiologies of abnormal LTs in an adult population in Jilin, China. METHODS: A total of 3791 individuals between the ages of 18 and 79 years were interviewed and then underwent ultrasonography and blood tests. RESULTS: The prevalence of abnormal LTs was 14.77% (560 out of 3791 subjects). The risk factors for abnormal LTs were non-alcoholic fatty liver disease (NAFLD) alone, which accounted for 11.61%, metabolic syndrome alone for 25%, or both for 22.14%. Abnormal LTs were more common in male than in female subjects. The development of abnormal LTs was correlated with older age males, increased daily alcohol intake, poor quality of sleep, smoking, fasting plasma glucose, body mass index, triglyceridemia, and low-density lipoprotein. Abnormal LTs in patients with metabolic syndrome and NAFLD were associated with high fasting plasma glucose, triglycerides, body mass index, low density lipoprotein, male, young age, poor sleep quality, smoking, and alcohol intake. However, abnormal LTs in patients with hepatitis B virus were associated with gender and increased age. CONCLUSIONS: The results from the current study demonstrated that the prevalence of abnormal LTs is high in the population (14.77%). Metabolic syndrome, NAFLD, and alcohol intake appear to be potentially important causes of the observed abnormal LTs.