[Analysis of the efficacy of the Ponseti method for treatment of secondary clubfoot in young children with tethered cord syndrome].

Objective: To explore the feasibility of Ponseti method in treatment of secondary clubfoot in young children with Tethered Cord Syndrome(TCS). Methods: The clinical data of 53 young children with clubfeet treated with Ponseti method from March 2014 to March 2017 at Department of Pediatric Orthopedics, the Third Affiliated Hospital of Zhengzhou University were analyzed retrospectively. These patients were divided into TCS group and Idiopathic group according to the etiology. There were 19 patients (33 feet) in TCS group,with an mean age of 2.8 months(range:0.2 to 24.0 months), including 13 males and 6 females, 5 patients with unilateral clubfeet and 14 patients with bilateral clubfeet. There were 34 patients (45 feet) in idiopathic group, with an mean age of 3.1 months(range: 0.1 to 21.0 months), including 18 males and 16 females, 23 patients with unilateral clubfeet and 11 patients with bilateral clubfeet. All the children received casts correction according to Ponseti method, and were followed up at 3 weeks, 3 months, 6 months and every 6 months after the Achilles tendon tenotomy or the last cast correction. Complications were recorded and therapeutic effect was evaluated of these children by Dimeglio Scoring System and the International Clubfoot Study Group (ICFSG) at the last follow-up. Independent t test, Mann-Witney U test or χ(2) test were used to compare the indicators of the two groups. Results: The number of plaster fixation in TCS group was (6.1±2.0) times, and that of idiopathic group was (4.8±1.0) times(t=3.482, P<0.01).In TCS group, 22 feet treated with Achilles tendon transection and that of idiopathic group was 40 feet(χ(2)=0.279, P=0.598). There were 18 cases recurrence in TCS group and 8 cases in Idiopathic group (t=11.149, P<0.01). In TCS group, 16 cases (27 feet) completed the initial correction, the success rate was 60.6% (27/33), 3 cases (6 feet) could not correct the deformity after 9 to 10 times of plaster fixation, and then underwent soft tissue release.In idiopathic group, 34 cases (45 feet) achieved initial correction after Ponseti treatment(χ(2)=6.488, P=0.011).At the last follow up, there were 5 cases (9 feet) in TCS group and 2 cases (2 feet) in idiopathic group underwent soft tissue release(χ(2)=6.110, P=0.013). The classification grade of ICFSG score of the two groups without soft tissue release were (2.1±0.6) and (1.8±0.7), the difference was not statistically significant (t=1.765, P=0.082). All the children had no skin ulceration, bedsores, skin allergy and other complications. Conclusion: Ponseti method is effective in the treatment of clubfoot secondary to TCS, and the functional recovery is similar to that of children with idiopathic clubfoot.

VASPIN reduces inflammation and endoplasmic reticulum stress of renal tubular epithelial cells by inhibiting HMGB1 and relieves renal ischemia-reperfusion injury.

OBJECTIVE: Renal ischemia-reperfusion injury (IRI) is a clinically common issue and the resulting acute kidney injury (AKI) seriously threatens the patient's life. Therefore, prevention and treatment of renal IRI are the key to alleviating AKI in such patients. The purpose of this study was to explore the effects of VASPIN on mouse renal IRI and human renal proximal tubular epithelial cells (HK-2 cells) to provide a new direction for the treatment of clinical renal IRI. MATERIALS AND METHODS: C57/BL6 mice were used to construct a renal IRI model and recombinant mouse VASPIN was subcutaneously injected to determine whether VASPIN can alleviate renal IRI in mice by histological examination and detection of mouse urine and serum related indicators. In addition, HK-2 cells were cultured and an IRI model was constructed at the cellular level by hypoxia reoxygenation to examine the effect and mechanism of VASPIN on endoplasmic reticulum stress (ERS) in HK-2 cells. RESULTS: Results revealed that in VASPIN-treated mice, edema of renal tubular epithelial cells was significantly improved and renal injury markers netrin-1 and L-FAPB were decreased in urine. In addition, VASPIN also reduced the expression of inflammatory factors in mouse serum and the level of oxidative stress in kidney tissue. The expression of ERS-related molecules (GRP78, ATF6, caspase12, and CHOP) in HK-2 cells treated with VASPIN was significantly reduced and VASPIN decreased the expression of the pro-inflammatory factor HMGB1. Moreover, VASPIN promoted the activity of the Nrf2/ARE/HO-1 signaling pathway and inhibited the NF-кB signaling pathway by inhibiting HMGB1. CONCLUSIONS: VASPIN reduces inflammation and ERS levels in kidney tissue and attenuates renal IRI by activating the Nrf2/ARE/HO-1 signaling pathway and inhibiting the NF-кB signaling pathway via inhibition of HMGB1.

Evaluation of the application of high volume hemofiltration in sepsis combined with acute kidney injury.

OBJECTIVE: To investigate the safety and effectiveness of the application of high-volume hemofiltration (HVHF) in children with sepsis combined with acute kidney injury. PATIENTS AND METHODS: A total of 76 child patients were enrolled and randomly divided equally (n=38) into control and the observation groups respectively. The control group received conventional volume hemofiltration (the ultrafiltration rate of 35-50 ml/kg/h), and the observation group received HVHF (50-100 ml/kg/h). RESULTS: The serum Interleukin-6 (IL-6), Tumor Necrosis Factor-a (TNF-α) and creatinine levels were significantly lower in the observation group than the control group at 6 h, 12 h, 24 h and 48 h of hemofiltration (p<0.05). The efficacy rate of treatment was improved. The mortality rate and incidence rate of complications were decreased, and the treatment course was significantly shortened (p<0.05). CONCLUSIONS: The application of HVHF in children with sepsis combined with acute kidney injury has a better safety and effectiveness.

Transmembrane 7 superfamily member 4 regulates cell cycle progression in breast cancer cells.

OBJECTIVE: TM7SF4 (transmembrane 7 superfamily member 4) gene encodes a seven-pass transmembrane protein that is primarily expressed in dendritic cells called as dendritic cell-specific expressed seven transmembrane protein (DC-STAMP). This protein regulates immunological functions, osteoclastogenesis and myeloid differentiation. Although the roles of TM7SF4 have been currently studied on Paget's disease of bone and papillary thyroid cancers, it is unclear whether TM7SF4 plays a role in breast cancer. In current study, we investigated the expression of TM7SF4 in human breast cancer cell lines. MATERIALS AND METHODS: In this study, five breast cancer lines were cultured. Small hairpin RNA against TM7SF4 using a lentiviral vector was generated and transfected into MCF-7 breast cancer cells. Effects of down-regulating TM7SF4 in transfected cells were examined by Western blot, RT-PCR, apoptotic rate, colony formation, and cell cycle analyses. RESULTS: The results demonstrated that down-regulation of TM7SF4 led to a decrease in colony formation in MCF-7 cells compared to the control group. This is likely due to a decrease in proliferation and cell cycle and an increase in apoptosis. CONCLUSIONS: To our knowledge, our data demonstrate for the first time that TM7SF4 plays an essential role in regulating cell cycle progression in breast cancer.

Palmatine, a protoberberine alkaloid, inhibits both Ca(2+)- and cAMP-activated Cl(-) secretion in isolated rat distal colon.

BACKGROUND AND PURPOSE: The protoberberine alkaloid berberine has been reported to inhibit colonic Cl(-) secretion. However, it is not known if other protoberberine alkaloids share these effects. We have therefore selected another protoberberine alkaloid, palmatine, to assess its effects on active ion transport across rat colonic epithelium. EXPERIMENTAL APPROACH: Rat colonic mucosa was mounted in Ussing chambers and short circuit current (I (SC)), apical Cl(-) current and basolateral K(+) current were recorded. Intracellular cAMP content was determined by an enzyme immunoassay. Intracellular Ca(2+) concentration was measured with Fura-2 AM. KEY RESULTS: Palmatine inhibited carbachol-induced Ca(2+)-activated Cl(-) secretion and the carbachol-induced increase of intracellular Ca(2+) concentration. Palmatine also inhibited cAMP-activated Cl(-) secretion induced by prostaglandin E(2) (PGE(2)) or forskolin. Palmatine prevented the elevation of intracellular cAMP by forskolin. Determination of apical Cl(-) currents showed that palmatine suppressed the forskolin-stimulated, apical cAMP-activated Cl(-) current but not the carbachol-stimulated apical Ca(2+)-activated Cl(-) current. Following permeabilization of apical membranes with nystatin, we found that palmatine inhibited a carbachol-stimulated basolateral K(+) current that was sensitive to charybdotoxin and resistant to chromanol 293B. However, the forskolin-stimulated basolateral K(+) current inhibited by palmatine was specifically blocked by chromanol 293B and not by charybdotoxin. CONCLUSIONS AND IMPLICATIONS: Palmatine attenuated Ca(2+)-activated Cl(-) secretion through inhibiting basolateral charybdotoxin-sensitive, SK4 K(+) channels, whereas it inhibited cAMP-activated Cl(-) secretion by inhibiting apical CFTR Cl(-) channels and basolateral chromanol 293B-sensitive, KvLQT1 K(+) channels.

Combined CD4+ Th1 effect and lymphotactin transgene expression enhance CD8+ Tc1 tumor localization and therapy.

Type 1 T cells are the major components in antitumor immunity. The lack of efficient CD8(+) cytotoxic T (Tc) cell infiltration of tumors is a major obstacle to adoptive Tc-cell therapy. We have previously demonstrated that adenovirus (AdV)-mediated transgene lymphotactin (Lptn) expression by intratumoral AdVLptn injection and intravenous CD4(+) helper T (Th) cell transfer can enhance Tc-cell tumor infiltration and eradication of early stage tumors (5 mm in diameter). In this study, we generated ovalbumin (OVA)-specific Tc1 and Th1 cells in vitro by incubation of OVA-pulsed dendritic cells with naive T cells from T-cell receptor (TCR) transgenic OT I and OT II mice. We then investigated the potential synergy of Th1 help effect and Lptn transgene expression in Tc1-cell therapy of well-established OVA-expressing EG7 solid tumors (7 mm in diameter). Our data showed that a combined adoptive T-cell therapy of Th1 (2.5 x 10(6) cells per mouse) and Tc1 (5 x 10(6) cells per mouse) resulted in regression of all eight (100%) transgene Lptn expressed EG7 tumors, which is significantly higher than four from eight (50%) in AdVLptn/Tc1 group and two from eight (25%) in Tc1/Th1 group (P < 0.05). The amount of transferred Tc1 cells detected in Lptn-expressed tumors with Th1 treatment is 0.72%, which is significantly higher than those of AdVLptn (0.22%), Th1 (0.41%) and the control AdVpLpA (0.09%) treatment groups (P < 0.05). Enhanced Tc1 tumor localization may be derived from the chemotactic effect of Lptn and the proliferative effect of Th1 and Lptn. This novel therapeutic strategy with enhancement of Tc1 tumor localization in the therapy of well-established tumors may become a tool of considerable conceptual interest in the implementation of future clinical objectives.

Use of the appendix to replace the choledochus.

Ten cases of choledochal cyst (CC) were treated by biliary-appendicoduodenostomy. The follow-up comprised a patient interview, ultrasonography (US), and single-proton ejected computerized tomography (SPECT) scanning. In all cases an anti-reflux submucosal tunnel was added to the distal appendico-duodenostomy; all showed an uneventful postoperative course. All the dilated intrahepatic bile ducts had normalized on B-US postoperatively. Four children under went SPECT examination; all of them had patent neo-bile ducts. In the authors' opinion: (1) Anastomosing the cecal end of the appendix to the common hepatic duct seemed more favorable than the other way around, because the cecal end could be easily trimmed to the size of the common hepatic duct, which was more or less dilated in the presence of a CC; (2) It is necessary to add a submucosal tunnel to the distal appendicoduodenostomy to achieve a more reliable anti-reflux effect; and (3) Transposing the vascularized appendix through the retro-transverse colon simplified the procedure and might reduce the risk of retroperitoneal complications if bile leakage should occur.

Primary hepatocellular carcinoma in women of mainland China. A clinicopathologic analysis of 104 patients.

The clinicopathologic characteristics of 104 hepatectomy samples from female patients with primary hepatocellular carcinoma (PHC) were compared with similar samples from 900 male patients with primary hepatocellular carcinoma; results of this comparison were studied. The male-to-female ratio was 8.7:1. The mean age of female patients with PHC was 46.2 years, which was approximately 3 years younger (49.1 years) than that of male patients with PHC. The frequency of associated liver cirrhosis (LC) was 49% in women with PHC and 68.2% in men with PHC (P < 0.01). The mean age of the female patients without LC was 43.2 years, more than 4 years younger (47.9 years) than that of the male patients. The mean ages of female and male patients with LC were 49.1 years and 49.8 years, 6 and 2 years older than that of their corresponding groups without LC, respectively. The positive rates of serum hepatitis B surface antigen (HBsAg) were 70.8% in the men and 59.7% in the women. The 5-year postoperative survival rates were 50% in the women and 25.7% in the men (P < 0.01). It is suggested that the development of PHC in women appears at a younger age than that of PHC in men in China and usually is associated with a lower frequency of LC and a more satisfactory postoperative prognosis.

Regulation of 1 alpha, 25-dihydroxyvitamin D3 synthesis in macrophages from arthritic joints by phorbol ester, dibutyryl-cAMP and calcium ionophore (A23187).

Phorbol 12-myristate 13-acetate (100 nM), a potent protein kinase C and macrophage activator, has a biphasic affect on 25(OH)D3-1 alpha-hydroxylase activity in synovial fluid macrophages from arthritis patients. After 5 h, 1 alpha, 25(OH)D3 synthesis fell from 5.2 +/- 0.1 to 1.6 +/- 0.2 pmol/h per 10(6) cells, however, after 24 h and 48 h, synthesis increased to 17.4 +/- 0.3 and 22.3 +/- 1.4 pmol/h per 10(6) cells, respectively. Although an independent short-term mechanism is suggested, protein kinase C may promote macrophage activation, thus increasing long-term 25(OH)D3-1 alpha-hydroxylase expression. Intracellular calcium and cAMP are unlikely to activate the enzyme, since 0.1 microM of the calcium ionophore, A23187, and 1 mM dibutyryl-cAMP inhibited synthesis by 87% and 79%, respectively, after 24 h.