[Analysis of the effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture].

Objective: To examine the feasibility and clinical effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture. Methods: This is a retrospective case series study. From February 2021 to February 2023, the clinical data of 24 patients (30 feet) with Achilles tendon contracture treated with all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening were analyzed retrospectively. There were 10 males and 14 females, aged (32.8±16.1) years (range: 9 to 62 years). There were 8 cases of left side only, 10 cases of right side only and 6 cases of bilateral. There were 14 cases (16 feet) of foot varus, 4 cases (6 feet) of foot valgus, and 6 cases (8 feet) without deformity. All patients underwent all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening. The surgical effects were evaluated using the maximum dorsal extension angle of ankle joint in knee extension position, the visual analogue scale (VAS) of pain, the American Orthopedic Foot and Ankle Society ankle-hindfoot score(AOFAS-AH). Paired sample t test was used to compare the scores before and after operation. Results: All patients successfully completed the operation, and the operation time of Achilles tendon lengthening was (22.0±5.7)minutes (range: 15 to 35 minutes) and the intraoperative blood loss was (6.5±2.7)ml (range: 2 to 15 ml). All patients primarily healing without any complications such as sural nerve injury, Achilles tendon rupture, important blood vessel injury, and obvious decrease of lift heel strength of achilles tendon. All 24 patients were followed up for (17.2±4.5) months (range: 12 to 28 months). One patient suffered from lift heel's weakness in one foot after operation, and recovered after repeated lift heel functional exercises. The ankle dorsiflexion function of two patients with calf triceps spasm were not improved after operation, and it was obviously improved after botulinum toxin injection. At the last follow-up, the maximum dorsal extension angle of ankle joint in knee extension position increased from -9.2°±7.6°(range:-25° to 5°) preoperatively to 14.5°±7.0°(range:0° to 28°)(t=24.83, P<0.01); the VAS score was reduced from (4.5±1.7) points (range:1 to 8 points) preoperatively to (1.5±0.9) points (range:0 to 3 points) (t=9.53, P<0.01), the AOFAS-AH was increased from (60.5±11.4)points (range:38 to 85 points) to (90.8±5.4) points (range:80-100 points)(t=14.21, P<0.01). Conclusions: All-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture not only provides Achilles tendon lengthening, but also avoids complications such as Achilles tendon rupture and sural nerve injury. It is an effective method for the treatment of Achilles tendon contracture.

[Posterior arthroscopic subtalar arthrodesis for symptomatic adult talocalcaneal coalition].

Objective: To investigate the functional outcomes of posterior arthroscopic subtalar arthrodesis (PASTA) for adult patients presenting with symptomatic talocalcaneal coalition. Methods: The study was a retrospective case-series research.The data of 17 adult patients (17 feet) with symptomatic talocalcaneal coalitions,treated with PASTA from March 2018 to February 2022 in Xuzhou Central Hospital were collected.This procedure involved 10 males and 7 females,aged (42.4±7.5) years(range:31 to 58 years).There were 9 cases on the right side and 7 cases on the left side.According to the Rozansky classification,there were 4 cases of type Ⅰ,7 cases of type Ⅱ, 3 cases of type Ⅲ,3 cases of type Ⅳ.The following items such as wound healing and bony union of the subtalar joint were observed.Clinical assessment was performed using pain visual analogue scale (VAS),American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores and 36-item short form health survey (SF-36) scores.The paired t test was used for data comparison. Results: The follow-up time was (24.8±6.9) months(range:12 to 40 months).There were no complications such as wound infection,deep vein thrombosis,nonunion,or screw breakage.One patient with preoperative spasm,relieved after the second surgical procedure (peroneal brevis tendon lengthening).The union time of the subtalar joint was (8.8±2.2) weeks(range:6 to 12 weeks).At the final follow-up,the VAS decreased from (6.4±1.3) to (1.3±0.9)(t=14.114,P<0.01), the AOFAS ankle-hindfoot score increased from (49.0±8.1) to (90.0±5.1)(t=38.782,P<0.01),and the SF-36 score increased from (50.8±9.5) to (91.0±4.9)(t=20.468,P<0.01). Conclusion: PASTA for adult patients presenting with symptomatic talocalcaneal coalition offers advantages of minimal trauma,fast recovery,and few complications,which is an effective method.

[Arthroscopic treatment of acute closed noninsertional rupture of Achilles tendon].

Objective: To investigate the clinical efficacy of arthroscopic treatment of acute closed noninsertional rupture of Achilles tendon. Methods: The clinical and imaging data of 30 patients (30 feet) with acute closed noninsertional rupture of Achilles tendon who were treated with all-inside arthroscopic technique at the Department of Hand and Foot Microsurgery,Xuzhou Central Hospital from June 2018 to June 2020 were analyzed retrospectively. There were 26 males and 4 females,aged (38.3±8.5)years old(range:19 to 66 years). There were 22 cases on the right side and 8 cases on the left side. The duration from injury to surgery was (2.1±1.4) days (range:1 to 7 days).All patients were treated with all-inside arthroscopic technique.The function of the ankle and the foot was assessed using visual analogue scale (VAS),the American Orthopaedic Foot & Ankle Society (AOFAS) ankle hindfoot scale and the Achilles tendon total rupture score (ATRS). The Arner-Lindholm score system was used to evaluate the excellent and good rate of clinical effect. Paired sample t test or rank-sum test was used for data comparison. Results: The patients were followed up for (18.6±2.2)months(range:12 to 28 months).All the wounds healed at the first stage.No complication such as infection,sural nerve injury or re-rupture happened.Two patinets felt mild pain after a long time exercise, and were alleviated by microwave therapy and stretching the Achilles tendon consistently.Another patient was unable to do a sustained single stance heel raise,which was recovered after repeated function practice.At the last follow-up,the VAS (M(IQR)) decreased from 6(5) preoperatively to 0(1)(Z=6.512,P<0.01),the AOFAS ankle hindfoot scale improved from 60.6±8.3 preoperatively to 96.3±4.8(t=-29.774,P<0.01),and the ATRS improved from 61.7±7.8 preoperatively to 97.1±2.3 (t=-53.661,P<0.01).According to the Arner-Lindholm score system,27 cases were excellent,3 cases were good,and the excellent and good rate was 100%. Conclusions: The all-inside arthroscopic technique not only ensures the quality of tendon ananstomosis,but also avoids injury to the sural nerve.It has the advantages of small trauma,faster recovery and fewer complications.

Rapid personalized chemotherapy recommendation for cancer patients: An interview with Shaohua Ma and two members of his group.

Shaohua Ma, an early-career group leader, and his team talk about their passion for data science and their project published in Patterns, where multiplex gene quantification-based "digital markers" are used for extremely rapid evaluation of chemo-drug sensitivity. This method allows quick and personalized chemo-drug recommendations for cancer patients, helping to improve their clinical care and health outcomes.

[The reconstruction of Myerson type â ¢ chronic Achilles tendon rupture by using the total arthroscopic technique combined with free semitendinosus tendon and gracilis tendon autograft].

Objective: To evaluate the clinical outcome of the reconstruction of Myerson type Ⅲ chronic Achilles tendon rupture by using the total arthroscopic technique combined with free semitendinosus tendon and gracilis tendon autograft. Methods: Clinical data of 32 patients(32 ankles) with Myerson type Ⅲ chronic Achilles tendon rupture who were treated by using the total arthroscopic technique combined with free semitendinosus tendon and gracilis tendon autograft at Department of Hand and Foot Microsurgery, Xuzhou Central Hospital from September 2013 to September 2018 were analyzed retrospectively.There were 28 males and 4 females, aged 45.5 years old(range: 22 to 69 years old), 12 cases in the right side and 20 in the left.All patients were treated by using the total arthroscopic technique combined with free semitendinosus tendon and gracilis tendon autograft for Myerson type Ⅲ chronic Achilles tendon rupture reconstruction.The functional recovery of the ankle was evaluated according to ankle-hindfood score of American Orthopaedic Foot and Ankle Society (AOFAS) Ankle Hindfoot Scale, Achilles tendon total rupture score (ATRS), visual analogue scale (VAS).Arner-Lindholm score was used to evaluate the excellent and good rate.The quantitative data were compared using t-test or Wilcoxon test. Results: The 32 patients were followed up for 33 months (range: 15 to 72 months).No serious postoperative complications such as infection, sural nerve injury or tend re-rupture outcomes were reported.Three patients complained of mild pain when after a minimum sitting, walking or jogging, which were completely relieved by simple physical therapy or continuous stretching of Achilles tendon.At the last follow-up, the VAS decreased from 3 (5) (M (Q(R)) ) preoperative to 0 (3) (Z=1.357, P<0.01) and AOFAS ankle hindfoot scale improved from 58.6±13.5 preoperative to 95.5±4.0 (t=16.9, P=0.00), ATRS improved from 47.5±9.3 preoperative to 96.6±3.3 (t=25.661, P<0.01).According to the score of Arner-Lindholm, 20 cases were excellent, 12 cases were good, and the excellent and good rate was 100%. Conclusion: The reconstruction of Myerson type Ⅲ chronic Achilles tendon rupture by using the total arthroscopic technique combined with free semitendinosus tendon and gracilis tendon autograft has the advantages of safety, reliability, effectiveness and minor injury.

[Arthroscopy-assisted percutaneous reduction and screw fixation for displaced intra-articular calcaneal fractures].

Objective: To investigate the surgical technology and clinical efficacy of using the all-inside arthroscopic treatment of intra-articular displaced calcaneal fracture. Methods: A retrospective analysis was made of 46 patients (46 feet) with intra-articular displaced calcaneal fractures treated by modified all-inside arthroscopic from December 2015 to December 2017 in Xuzhou Central Hospital. Twenty-eight cases (28 feet) were male and 18 cases (18 feet) were female, aged from 19 to 60 years (mean (39±13) years). The time from injury to operation was 1 to 10 days (mean (4.5±2.2) days). The pre-operative visual analogue scale (VAS) of pain ranged from 4 to 8 points, mean (6.3±1.8) points. No other combined injuries were found in the affected feet in all patients. All patients were treated with anterolateral, lateral and posterolateral approaches of arthroscopically assisted reduction for calcaneal fractures, and fixed with hollow screw. Main outcome measures included the pain, foot appearance, and the scores of the American Orthopedic Foot & Ankle Society (AOFAS) Scale and the Maryland Scale. Paired t test was used when the data before and after the operation were compared. Results: All incisions healed in one stage without postoperative complications such as nerve, vessel and tendon injury. The mean follow-up period ranged from 12 to 36 months, mean (21±9) months. Postoperatively X-ray showed complete fracture healing time was 8 to 12 weeks, mean (10.4±2.3) weeks. At the last follow-up, the ankle and talocalcaneal joints movement and appearance were ideal, and no traumatic arthritis was found. The VAS score of talocalcaneal joint was 0. AOFAS score increased from 58±13 to 96±9 and Maryland score increased from 72±11 to 98±8 after the operation, the differences were all significant (t=15.958, 12.496, both P<0.05). Conclusion: The all-inside arthroscopic treatment of the intra-articular displaced calcaneal fracture is an effective and precise method, with accurately outcomes, precise reduction and minimally postoperative complications.

[Analysis of the effect of two medial portals for the all-inside endoscopic treatment of recalcitrant plantar fasciitis].

Objective: To examine the clinical effect of all-inside endoscopic treatment of recalcitrant plantar fasciitis through two medial portals. Methods: The recalcitrant plantar fasciitis data of 67 cases (79 feet) that underwent two medial portals all-inside endoscopic treatment at Department of Hand and Foot Microsurgery, Xuzhou Central Hospital from October 2016 to June 2018 were retrospectively analyzed.There were 24 males (30 feet) and 43 females (49 feet) aged 44.3 years old(range:24-76 years).The mean disease duration from the specialist doctor intervention to operation was (23.7±11.0) months (range: 12-60 months). All the patients were treated with the two medial portals all-inside endoscopic procedure when the 6 months conservative treatment had failed.The endoscopic procedure including debridement and partial plantar fasciotomy.The clinical results,including pain,activity,gait and foot health quality,were scored using visual analogue pain scale (VAS),American Orthopaedic Foot & Ankle Society Ankle Hindfoot Scale (AOFAS) and SF-36. Results: All the patients were followed up for (15.2±6.7) months (range: 12-24 months). All cases achieved primarily healing of the wound without postoperative complications of nerve,vessel and tendon.At the last follow-up,the VAS decreased from (5.3±2.0) preoperative to 0 prooperative (t=21.60, P=0.000), AOFAS increased from (72.6±9.4) to (97.3±4.6)(t=19.43,P=0.000),SF-36 increased from (93.6±8.4) to (119.1±7.3) (t=18.78, P=0.000), non-recurrent calcaneal spur, normal foot and ankle activity was recorded. Conclusion: The two medial portals all-inside endoscopic procedure is effective for the treatment of recalcitrant plantar fasciitis.

Clinical effect of E-series of prostaglandin receptor 2 and epidermal growth factor receptor signal pathways in the development of esophageal squamous cell carcinoma.

Signal pathways mediated by epidermal growth factor receptor (EGFR) and E-series of prostaglandin receptors (EPs) are closely correlated to the pathogenesis of tumor. This experiment was designed to investigate the expression and clinical significance of EP2 and EGFR in esophageal squamous cell carcinoma (ESCC). Tissue samples were collected reterospectively from 87 patients with ESCC (first diagnosed). The patients were followed up for 5 years after radical surgery. The expression of EP-2 and EGFR were examined by tissue chip technology and immunohistochemistry methods. Clinicopathological and prognostic impact were evaluated. Overexpression of EGFR and EP-2 was more observed in ESCC than the control group (58.6% vs. 13.9%; 52.9% vs. 4.88%, P < 0.001, respectively); which correlated with tumor infiltration depth, lymph node metastasis, and tumor-lymph node-metastasis staging. Both the EP-2 and EGFR overexpression were detected in 39 specimens and exhibited the positive correlation (P < 0.001, r = 0.404). Overexpression of EP2 and EGFR exhibited significant correlation with worse 5-year overall survival than those with negative result (17.6% vs. 27.8%, P = 0.011; 10.9% vs. 34.1%, P < 0.001, respectively). Cox proportional hazard model showed that the T-staging, lymph node metastasis, and EGFR overexpression were the independent risk factors of the prognosis. The present study exhibited that the overexpression of EP2 and EGFR in ESCC tissues might play an important role in carcinogenesis and the progression of ESCC.

Pharmacological chaperone therapy by active-site-specific chaperones in Fabry disease: in vitro and preclinical studies.

Many genetic disorders are due to protein misfolding and excessive premature degradation in the endoplasmic reticulum (ER). When a gene mutation does not affect the functionality of the protein, it may still promote the premature clearance of the protein by ER-associated degradation (ERAD), resulting in a loss of function. Competitive inhibitors are often effective active-site-specific chaperones when used at sub-inhibitory concentrations. Active-site-specific chaperones assist in the folding of mutant lysosomal enzymes in the ER, thereby promoting their escape from ERAD, enhancing trafficking to the lysosome and increasing the level of residual enzyme activity. In Fabry disease, degradation of various mutant forms of a-galactosidase A (alpha-gal A) has been shown to take place in the ER as a result of protein misfolding. One of the most potent inhibitors of alpha-gal A, 1-deoxygalactonojirimycin, has also been shown to be effective in enhancing residual alpha-gal A activity in cultured fibroblasts and lymphoblasts established from patients with Fabry disease caused by a variety of missense mutations. Oral administration of 1-deoxygalactonojirimycin to transgenic mice expressing a mutant form of human alpha-gal A (R301Q) yielded higher alpha-gal A activity in major tissues, compared with untreated transgenic mice.

Suppression of PPN/MG61 attenuates Wnt/beta-catenin signaling pathway and induces apoptosis in human lung cancer.

Wingless and int homologue (Wnt) family proteins have been shown to have important roles in the decision of cell fate and behavior at multiple stages during the development and tumorigenesis. One of the Drosophila segment polarity genes, porcupine (porc) gene, encodes an evolutionarily conserved endoplasmic reticulum membrane protein involving in the post-translational processing of the Wnt family proteins. Here, we report that human homologue of Drosophila porc gene, PPN/MG61, was abundantly expressed in human cancer cell lines, but not in normal cells. We also found that PPN/MG61 was overexpressed in primary lung cancer tissue samples, compared to their matched normal tissue samples. Furthermore, when we used small interfering RNA to knock down PPN/MG61 mRNA in lung cancer cells expressing the gene, we observed apoptosis induction, along with decreased activity of Wnt pathway in those lung cancer cells. These data suggest that PPN/MG61 may be a novel marker for human lung cancer and that post-translational modification of the Wnt signal molecules by PPN/MG61 may be important for the function of Wnt pathway in lung cancer.

In vitro inhibition and intracellular enhancement of lysosomal alpha-galactosidase A activity in Fabry lymphoblasts by 1-deoxygalactonojirimycin and its derivatives.

Fabry disease is a lysosomal storage disorder caused by deficient lysosomal alpha-galactosidase A (alpha-Gal A) activity. Deficiency of the enzyme activity results in progressive deposition of neutral glycosphingolipids with terminal alpha-galactosyl residue in vascular endothelial cells. We recently proposed a chemical chaperone therapy for this disease by administration of 1-deoxygalactonojirimycin, a potent inhibitor of the enzyme, at subinhibitory intracellular concentrations [Fan, J.-Q., Ishii, S., Asano, N. and Suzuki, Y. (1999) Nat. Med. 5, 112-115]. 1-Deoxygalactonojirimycin served as a specific chaperone for those mutant enzymes that failed to maintain their proper conformation to avoid excessive degradation. In order to establish a correlation between in vitro inhibitory activity and intracellular enhancement activity of the specific chemical chaperone, a series of 1-deoxygalactonojirimycin derivatives were tested for activity with both alpha-Gal A and Fabry lymphoblasts. 1-Deoxygalactonojirimycin was the most potent inhibitor of alpha-Gal A with an IC50 value of 0.04 microM. alpha-Galacto-homonojirimycin, alpha-allo-homonojirimycin and beta-1-C-butyl-deoxygalactonojirimycin were effective inhibitors with IC50 values of 0.21, 4.3 and 16 microM, respectively. N-Alkylation, deoxygenation at C-2 and epimerization at C-3 of 1-deoxygalactonojirimycin markedly lowered or abolished its inhibition toward alpha-Gal A. Inclusion of 1-deoxygalactonojirimycin, alpha-galacto-homonojirimycin, alpha-allo-homonojirimycin and beta-1-C-butyl-deoxygalactonojirimycin at 100 microM in culture medium of Fabry lymphoblasts increased the intracellular alpha-Gal A activity by 14-fold, 5.2-fold, 2.4-fold and 2.3-fold, respectively. Weaker inhibitors showed only a minimum enhancement effect. These results suggest that more potent inhibitors act as more effective specific chemical chaperones for the mutant enzyme, and the potent competitive inhibitors of alpha-Gal A are effective specific chemical chaperones for Fabry disease.

Role of Ser-65 in the activity of alpha-galactosidase A: characterization of a point mutation (S65T) detected in a patient with Fabry disease.

Fabry disease is a genetic disorder caused by deficient activity of alpha-galactosidase A (alpha-Gal A). Recent gene analysis of a Fabry patient revealed a point mutation (S65T) resulting in a significant decrease of enzyme activity (Chen, C.-H., et al. (1998) Hum. Mutat. 11, 328-330). In order to evaluate the role of Ser-65 in the alpha-Gal A activity and the molecular mechanism of its deficient enzyme activity in mammalian cells, we prepared gene products of S65T, S65A, and E66D mutations of alpha-Gal A by using an expression system with baculovirus/insect cells and characterized the kinetic and physical properties of those purified enzymes. The Km values of mutant enzymes were 3.5 (S65T), 3.4 (S65A), and 2.3 mM (E66D), using 4-methylumbelliferyl alpha-D-galactoside as a substrate, and the Vmax values were 2.7 x 10(6) (S65T), 3.4 x 10(6) (S65A), and 2.5 x 10(6) units/mg (E66D), respectively, which were similar to those of the normal enzyme (Km, 2.3 mM; Vmax, 2.3 x 10(6) units/mg). The in vitro stability of mutant enzymes at neutral pH was significantly reduced (S65T, 4% of normal; S65A, 29%; E66D, 54%). The intracellular alpha-Gal A activities of S65T, S65A, and E66D in COS1 cells transfected with corresponding plasmid DNAs were markedly lower than the normal enzyme activity (9, 26, and 68% of normal, respectively). However, intracellular enzyme activities were enhanced to 34% (S65T), 44% (S65A), and 80% (E66D) of normal, respectively, by cultivation of the cells with 20 microM 1-deoxygalactonojirimycin (a potent inhibitor of alpha-Gal A) for 24 h. These results suggest that Ser-65 is responsible for the stability of alpha-Gal A but not for the enzyme function.

Accelerated transport and maturation of lysosomal alpha-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor.

Fabry disease is a disorder of glycosphingolipid metabolism caused by deficiency of lysosomal alpha-galactosidase A (alpha-Gal A), resulting in renal failure along with premature myocardial infarction and strokes. No effective treatment of this disorder is available at present. Studies of residual activities of mutant enzymes in many Fabry patients showed that some of them had kinetic properties similar to those for normal alpha-Gal A, but were significantly less stable, especially in conditions of neutral pH (refs. 3-5). The biosynthetic processing was delayed in cultured fibroblasts of a Fabry patient, and the mutant protein formed an aggregate in endoplasmic reticulum, indicating that the enzyme deficiency in some mutants was mainly caused by abortive exit from the endoplasmic reticulum, leading to excessive degradation of the enzyme. We report here that 1-deoxy-galactonojirimycin (DGJ), a potent competitive inhibitor of alpha-Gal A, effectively enhanced alpha-Gal A activity in Fabry lymphoblasts, when administrated at concentrations lower than that usually required for intracellular inhibition of the enzyme. DGJ seemed to accelerate transport and maturation of the mutant enzyme. Oral administration of DGJ to transgenic mice overexpressing a mutant alpha-Gal A substantially elevated the enzyme activity in some organs. We propose a new molecular therapeutic strategy for genetic metabolic diseases of administering competitive inhibitors as 'chemical chaperons' at sub-inhibitory intracellular concentrations.

Release of T-antigen, a carcinoma marker from native human cells, by endo-alpha-N-acetylgalactosaminidase of Alcaligenes sp.

The endo-alpha-N-acetylgalactosaminidase from Alcaligenes sp. could release T-antigen (Ga1 beta 1----3GalNAc), a carcinoma-associated marker from asialo glycophorin and human cells. The released T-antigen from human asialo erythrocytes was determined by thin layer chromatography and gas liquid chromatography. The released T-antigen from human gastric carcinoma cell Kato III was identified by high performance liquid chromatographies with a reverse-phase column and a size fractionation column. Released T-antigen could be analyzed quantitatively by a sensitive method including pyridylamino derivatization and following high performance liquid chromatography. This suggests that the enzyme is useful for detection and determination of T-antigen from cells.