[Drug research and development and unmet needs for advanced-stage hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and is a global health challenge. Radical surgical resection is the most effective method to achieve long-term survival for HCC. Regrettably, the vast majority of HCC patients lose the opportunity for radical resection at the time of diagnosis due to advanced tumors or poor liver reserve capacity. HCC is resistant to conventional chemotherapy, and in the past, there have been no definite and effective systemic therapeutic drugs. Fortunately, over the last decade, the research and development of molecular targeted therapy and immunotherapy drugs for HCC have made rapid progress, and a variety of drugs and combination therapy regimens have been successively approved for clinical use. However, the overall therapeutic effect is still not ideal and needs further improvement.

[Clinical and endoscopic characteristics of adult celiac disease].

Objective: The study aimed to analyze the clinical and endoscopic characteristics of adult celiac disease (CD) to provide a scientific basis for more effective CD diagnosis and treatment. Methods: In this cross-sectional study, the clinical and endoscopic data of 96 adult CD patients treated in the Department of Gastroenterology of the People's Hospital of Xinjiang Uygur Autonomous Region from March 2016 to December 2021 were retrospectively collected and analyzed. Results: A total of 96 CD patients were diagnosed, including 33 men and 63 women. The average age was 47±14 years (range, 18-81 years). The disease occurred mainly in the age group of 31-60 years. The median course of the disease was 2.0 (0.2-40.0) years. There were 41 (42.7%) classical and 55 (57.3%) non-classical CD patients. All patients with classical CD showed chronic diarrhea, often accompanied by abdominal pain (46.3%, 19/41), abdominal distension (17.1%, 7/41), anemia (65.9%, 27/41), and chronic fatigue (48.8%, 20/41). The main manifestations of non-classical CD were chronic abdominal pain (58.2%, 32/55), abdominal distension (32.7%, 18/55), anemia (40.0%, 22/55), and osteopenia/osteoporosis (38.2%, 21/55). Compared with non-classical CD, anemia developed more frequently in classical CD, and the difference was statistically significant (P = 0.012). The incidence of complications in CD patients was 36.5% (35/96), and the main complications were thyroid disease (19.8%, 19/96), connective tissue disease (6.2%, 6/96), and kidney disease (6.2%, 6/96). There was no significant difference between classical and non-classical CD (P>0.05). The frequency of endoscopic manifestations in CD patients was 84.4% (81/96). Duodenal bulb endoscopy showed nodular changes (72.9%, 70/96), grooved changes (10.4%, 10/96), and focal villous atrophy (9.4%, 9/96). The main manifestations of descending endoscopy were the decrease, flattening, or disappearance of duodenal folds (43.8%, 42/96), scallop-like changes (38.5%, 37/96), and nodular changes (34.4%, 33/96). Conclusions: Adult CD patients are mostly female. CD occurred mainly in the age group of 31-60 years. The clinical manifestations were mainly those of non-classical CD. Some patients often had other autoimmune diseases. Patients with characteristic endoscopic manifestations should be warned about the possibility of developing CD. Clinicians should strengthen the understanding of CD and reduce the related rates of missed diagnosis.

[The influence of HBsAg expression in liver tissue on the postoperative recurrence of HCC patients].

Objective: To investigate the influence of HBsAg expression in peritumoral tissue of hepatocellular carcinoma (HCC) patients on their postoperative recurrence. Methods: The HCC patients treated in Shanghai Eastern Hepatobiliary Surgery Hospital from October 2009 to August 2010 were selected. The clinicopathological data and adjacent tissues of 718 patients were collected, and dextran polymer immunohistochemical staining was used to detect the expression of HBsAg in adjacent tissues. According to the expression of HBsAg in adjacent tissues, the tissues were divided into HBsAg positive group and HBsAg negative group. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: Among the 718 patients in the whole group, 153 were HBsAg negative and 565 were HBsAg positive. There was a statistically significant difference in serum HBV DNA level between HBsAg-positive and HBsAg-negative patients (P<0.001). The number of patients with serum DNA≥2 000 IU/ml and<2 000 IU/ml in HBsAg negative group were 52 and 93, while the patients in HBsAg positive group were 325 and 205. The cumulative recurrence rates of all patients at 1, 3, and 5 years after surgery were 30.2%, 54.3%, and 62.7%, respectively. The expression of HBsAg was related to the recurrence (P=0.038). Multivariate analysis showed that γ-GT, PT, multiple tumors, tumor length, and portal vein invasion were independent risk factors for recurrence of HCC (P<0.05). In HBeAg-negative patients with low viral load (HBV DNA <2 000 IU/ml) and without cirrhosis, the recurrence rates of HBsAg-positive patients were 14.3% and 31.0% at 3 and 5 years, respectively, compared with HBsAg negative patients (all 0), the difference was statistically significant (P=0.021). Conclusion: The positive expression of HBsAg in peritumoral tissue increases the postoperative recurrence risk of HCC patients.

New α-Emitting Isotope

A new α-emitting isotope ^{214}U, produced by the fusion-evaporation reaction ^{182}W(^{36}Ar,4n)^{214}U, was identified by employing the gas-filled recoil separator SHANS and the recoil-α correlation technique. More precise α-decay properties of even-even nuclei ^{216,218}U were also measured in the reactions of ^{40}Ar, ^{40}Ca beams with ^{180,182,184}W targets. By combining the experimental data, improved α-decay reduced widths δ^{2} for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N=126 are deduced. Their systematic trends are discussed in terms of the N_{p}N_{n} scheme in order to study the influence of proton-neutron interaction on α decay in this region of nuclei. It is strikingly found that the reduced widths of ^{214,216}U are significantly enhanced by a factor of two as compared with the N_{p}N_{n} systematics for the 84≤Z≤90 and N<126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the π1f_{7/2} and ν1f_{5/2} spin-orbit partner orbits, which is supported by the large-scale shell model calculation.

Temperature-Induced Lifshitz Transition and Possible Excitonic Instability in ZrSiSe.

The nodal-line semimetals have attracted immense interest due to the unique electronic structures such as the linear dispersion and the vanishing density of states as the Fermi energy approaching the nodes. Here, we report temperature-dependent transport and scanning tunneling microscopy (spectroscopy) [STM(S)] measurements on nodal-line semimetal ZrSiSe. Our experimental results and theoretical analyses consistently demonstrate that the temperature induces Lifshitz transitions at 80 and 106 K in ZrSiSe, which results in the transport anomalies at the same temperatures. More strikingly, we observe a V-shaped dip structure around Fermi energy from the STS spectrum at low temperature, which can be attributed to co-effect of the spin-orbit coupling and excitonic instability. Our observations indicate the correlation interaction may play an important role in ZrSiSe, which owns the quasi-two-dimensional electronic structures.

Short-Lived α-Emitting Isotope

A new, very short-lived neutron-deficient isotope ^{222}Np was produced in the complete-fusion reaction ^{187}Re(^{40}Ar,5n)^{222}Np, and observed at the gas-filled recoil separator SHANS. The new isotope ^{222}Np was identified by employing a recoil-α correlation measurement, and six α-decay chains were established for it. The decay properties of ^{222}Np with E_{α}=10016(33) keV and T_{1/2}=380_{-110}^{+260} ns were determined experimentally. The α-decay systematics of Np isotopes is improved by adding the new data for ^{222}Np, which validates the N=126 shell effect in Np isotopes. The evolution of the N=126 shell closure is discussed in the neutron-deficient nuclei up to Np within the framework of α-decay reduced width.

New Isotope

A new short-lived neutron-deficient isotope ^{220}Np was synthesized in the fusion-evaporation reaction ^{185}Re(^{40}Ar,5n)^{220}Np at the gas-filled recoil separator SHANS. Based on the measurement of the correlated α-decay chains, the decay properties of ^{220}Np with E_{α}=10040(18) keV and T_{1/2}=25_{-7}^{+14} µs were determined, which are in good agreement with theoretical predictions. From the new experimental results coupled with the recently reported α-decay data of ^{219,223}Np, the α-decay systematics for Np isotopes around N=126 was established, which allows us for the first time to test the robustness of the N=126 shell closure in Z=93 Np isotopes. The results also indicate that, in the region of nuclei with Z≥83, the proton drip line has been reached for all odd-Z isotopes up to Np.

Association of serum uric acid change with mortality, renal function and diuretic dose administered in treatment of acute heart failure.

BACKGROUND AND AIMS: Hyperuricemia is reportedly associated with poor outcome in acute heart failure (AHF). The association between changes in Uric acid (UA) levels with renal function change, diuretic doses, and mortality in patients with AHF were studied. METHODS AND RESULTS: Consecutive patients hospitalized with AHF were reviewed (n = 535). UA levels were measured at admission and either at discharge or on approximately the seventh day of admission. Patients with an UA change in the top tertile were defined as having an increase (UA-increase) and were compared to those outside the top tertile (non-UA-increase). The endpoint was all-cause mortality, with a mean follow-up duration of 22.2 months. Patients in the UA-increase group presented with greater creatine increase (P < 0.001), and were administered a higher average daily dose of loop diuretic (P = 0.016) compared with the non-UA-increase group. In-hospital UA-increase was associated with higher risk of mortality even after adjusting for confounding variables including creatine change and diuretic dosage [harzard ratio (HR) 1.53, 95% confidence interval (CI) 1.02-2.30, P = 0.042]. In patients with hyperuricemia on admission, UA-increase was associated with increased mortality (adjusted HR 2.21, 95% CI 1.38-3.52, P = 0.001). Whereas, in those without admission hyperuricemia, UA-increase had no significant association with mortality. CONCLUSIONS: An increase in UA during in-hospital treatment is associated with an increase in creatine levels and daily diuretic dose. Mortality associated with increased UA is restricted to patients who already have hyperuricemia at admission. A combination of UA levels at admission and UA changes on serial assessment during hospitalization may be additional value in the risk stratification of AHF patients.

[Advances in the study of programmed cell death protein 1 and its ligand inhibitors in the treatment of late stage HCC].

The treatment of late stage hepatocellular carcinoma (HCC) presently remains a great challenge. A very few drugs have been recently approved for clinical use except sorafenib and lenvatinib. After decades of failure and experience with molecular targeted and immunosuppressive therapy, immune checkpoint inhibitors are becoming one of the potentially effective therapies for patients with HCC, whose tumor is in the middle and late stages. Moreover, immune checkpoint is one of the main mechanisms of tumor immune evasion; of which programmed cell death protein 1 and its ligand (PD1/PD-L1) are important immune checkpoint targets, and its related pathway has shown to have an antitumor effect in a variety of solid or hematologic tumors and its inhibitors can effectively exert antitumor immunosuppressive effects. This review summarizes the current role of PD1/PD-L1 inhibitors in the treatment of late stage HCC, and explores the forecasting value of combined therapy strategy for HCC.

[A comparative study of intrahepatic cholangiocarcinoma and hepatocellular carcinoma with reference to clinical features and prognosis].

Objective: To comparatively study intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) with reference to clinical features and prognosis in Chinese Han population. Methods: 699 cases of HCC and 170 cases of ICC confirmed by surgical pathological files from 2009 to 2010 were included and followed-up. The differences in demographic characteristics, hepatitis B virus infection, clinical characteristics, biochemical indexes, tumor markers and prognosis of HCC and ICC were analyzed retrospectively by means of paired t-test, analysis of variance, chi-square test and Pearson's correlation coefficient. Results: Among 869 cases of primary liver cancer, HCC and ICC accounted for 80.43% and 19.57%. The old aged (P < 0.001) male incidence of HCC was higher than that of ICC (P < 0.001). The infection rates of hepatitis B virus were 89.84% and 35.88% in HCC and ICC, respectively, and the infection rates of hepatitis B, serum HBsAg postive rate and DNA account in HCC were higher than ICC (P < 0.001). The incidence of liver cirrhosis and hepatic schistosomiasis in HCC was also significantly different from that in ICC (both P < 0.01). Pearson's correlation analysis showed that there was a significant negative correlation between HCC or ICC tumor type and hepatic schistosomiasis (r = -0.018, P < 0.001), and there was a significant positive correlation between HCC and hepatic cirrhosis (r = 0.179, P < 0.001, and r = 0.528, P < 0.001, respectively). However, the proportion of cirrhosis and schistosomiasis in hepatitis B positive ICC cases was not significantly different from that in HCC cases (P > 0.05). Among the biochemical indicators, there were significant differences between HCC and ICC in the abnormal rate of ALT(P < 0.01), AST(P < 0.05), ALP (P < 0.01), GGT (P < 0.01) and TBIL (P < 0.01) while there was no significant difference between ALB and pre-ALB (P > 0.05) in HCC and ICC groups. The content and abnormal rate of alpha-fetoprotein were higher in HCC (P < 0.01), while the content and abnormal rate of carcinoembryonic antigen and carbohydrate antigen 19-9 were higher in ICC (P < 0.01). The 10-year survival rate and median survival time (46.92% and 80.3 months) of HCC were higher than those of ICC (12.57% and 12.4 months) (P < 0.01). Conclusion: In the study population, compared with ICC cases, the old aged male HCC cases are more common and has higher infection rate of hepatitis B virus and cirrhosis, but liver schistosomiasis is less common. The inflammatory damage, secretion and metabolic function of HCC were different from that of ICC cases, while the synthetic reserve function was similar to that of ICC and the prognosis of HCC cases was significantly better. The incidence of cirrhosis and schistosomiasis in ICC cases with positive hepatitis B virus infection was not significantly different from that of HCC cases.

[Advances in the application of artificial intelligence in cancer diagnosis and treatment].

The application of artificial intelligence is developing rapidly in various fields with the improvement of computing power, big data processing, and diversity of algorithms. It has a great potential value in the field of medical and healthcare, especially in the field of cancer diagnosis and treatment. In addition, it can analyze a large amount of data, information, and knowledge instantaneously. Therefore, it serves as a powerful tool for doctors to make the best treatment decisions. Notably, the development of science and technology truly transform into the actual interests of patients. This paper introduces advances in the application of artificial intelligence in diagnosis and treatment of cancer through digital pathology, medical imaging, and genomic medicine.

[A retrospective analysis of clinical characteristics and outcomes of heart failure patients with different left ventricular ejection fractions].

Objective: To compare the clinical characteristics, and outcomes of patients with heart failure with different left ventricular ejection fractions (LVEF). Methods: A total of 1 182 hospitalized patients with heart failure (HF) were enrolled and retrospectively studied in the present study. The patients were stratified by LVEF as reduced (HFrEF, LVEF<40%, n=313), mid-range (HFmrEF, 40% ≤LVEF <50%, n=287) and preserved (HFpEF, LVEF≥50%, n=582) ejection fraction groups. Among the 1 182 cases, 941 of them (81.3%, 84.9%, and 84.0% inHFrEF, HFmrEF and HFpEF groups, respectively) were followed up for an median duration of 27.3 months. Results: (1) Among the study patients, 26.5% were in HFrEF, 24.3% in HFmrEF, and 49.2% in HFpEF groups. (2) Ischemic heart disease with HFmrEF was more frequent than that in patients with HFrEF. The average age, percentage of female subjects, systolic blood pressure, uric acid, N terminal B-type natriuretic peptide precursor (NT-proBNP), hemoglobin, and the incidence of hypertensive heart disease, anemia, atrial fibrillation in patients with HFmrEF were higher than those in patients with HFrEF, but lower than those in patients with HFpEF (all P<0.01). (3) The all-cause cumulative mortality was 10.8% at 1 year, 20.6% at 2 years and 35.9% at 5 years. No difference was observed in the all-cause cumulative mortality at 1 year, 2 years, 5 years among the three groups (all P>0.05). Conclusions: The HFmrEF patients, as a new and distinct group, were with many intermediate characteristics compared with HFrEF and HFpEF subjects. However, the all-cause mortality was not significantly different among HF patients with different LVEF.

[Efficacy and safety of ultrasound-guided or neurostimulator-guided bilateral axillary brachial plexus block].

Objective: To explore the efficacy and safety of bilateral axillary brachial plexus block under the guidance of ultrasound or neurostimulator. Methods: From February 2012 to April 2014, 120 patients undergoing bilateral hand/forearm surgery in Beijing Jishuitan Hospital were enrolled and anaesthetized with bilateral axillary brachial plexus block. All patients were divided into two groups randomly using random number table: the ultrasound-guided group (group U, n=60) and the neurostimulator-guidedgroup (group N, n=60). The block was performed with 0.5% ropivacaine. Patients' age, sex and operation duration were recorded. Moreover, success rate, performance time, onset of sensor and motor block, performance pain, patient satisfaction degree and the incidence of related complications were also documented. Venous samples were collected at selected time points and the total and the plasma concentrations of ropivacaine were analyzed with HPLC. Results: The performance time, the onset of sensor block and the onset of motor block of group U were (8.2±1.5), (14.2± 2.2)and (24.0±3.5)min respectively, which were markedly shorter than those in group N( (14.6±3.9), (19.9±3.8), (28.8±4.2)min, respectively), and the differences were statistically significant(t=11.74, 10.09, 6.73, respectively, all P<0.01). The performance pain score of group N was (25.5± 13.2), which was obviously more serious than group U (31.7± 11.2) and a significant statistical difference was detected (t=2.856, P<0.05). The patient satisfaction degree of group U was 95.0%, which was significantly higher than group N (83.3%) and a markedly statistical difference was detected (χ(2)=4.227, P<0.05). Fifty min after performance, the total plasma concentration of ropivacaine of group U was(1.76±0.48)mg/L, which was significantly lower than group N (1.88±0.53)mg/L and a significant statistical difference was detected (t=2.43, P<0.05), while no significant differences were detected at the other time points between two groups (P>0.05). No analgesic was superadded and no other anesthesia methods were applied. No complications were detected perioperatively. Conclusions: The bilateral axillary brachial plexus block under the guidance of ultrasound or neurostimulator are both effective and safe for bilateral hand/forearm surgery. However, the ultrasound-guided block may be more clinically beneficial because of its shorter performance time, rapid onset and higher patient satisfaction degree.

[Modern knowledge and development trend of intrahepatic cholangiocellular carcinoma].

Although intrahepatic cholangiocellular carcinoma (ICC) has a relatively low incidence rate, it ranks the second in the most common primary malignant liver tumors, with hepatocellular carcinoma ranking the first. Meanwhile, its incidence and mortality rates tend to increase significantly in the past decades. On the one hand, due to a lack of characteristic clinical symptoms, specific tumor markers, and imaging findings, early diagnosis of ICC is extremely difficult; on the other hand, ICC has highly malignant biological behaviors and early extrahepatic metastasis, so patients often experience early recurrence even if surgical resection is performed, which leads to the poor prognosis of such patients. Unfortunately, since ICC has a low incidence rate and relatively few patients, it is not taken seriously in clinical practice. Since there is a lack of clinical data, specimens, and in-depth studies on ICC, its pathogenesis remains unclear. This article discusses recent advances in ICC, including risk factors, molecular mechanism, new diagnostic markers, and therapies (including molecular targeted drugs).

The prevalence of migraine in university students: a systematic review and meta-analysis.

Our aim was to determine the prevalence of migraine amongst university students. Migraine is highly prevalent amongst university students, but the exact frequency remains inconsistent between studies. PubMed, Embase and Google Scholar databases were used to identify studies dealing with the prevalence of migraine amongst university students published between 1 January 1988 and 31 August 2014. The pooled migraine prevalence was calculated using DerSimonian and Laird's random-effects model. Heterogeneity of the results was investigated using subgroup analysis and the trend of migraine prevalence according to the publication year and sample size was determined by cumulative analysis. Data were combined from 56 independent studies, analysing a total of 34,904 students. The pooled migraine prevalence was 16.1% [95% confidence interval (CI) 13.6%-18.9%]: 11.3% (95% CI 8.8%-14.4%) amongst male students and 21.7% (95% CI 18.0%-25.8%) amongst female students. Subgroup analysis revealed that diagnostic criteria (P < 0.0001) and gender distribution (P = 0.004) significantly affected migraine prevalence. Cumulative analysis found that the 95% CI became narrower with ascending publication year and sample size. Many studies agree that migraine is highly prevalent amongst university students, but diverse methodologies lead to substantial heterogeneity in the results. It is shown that gender and diagnostic criteria significantly influence the migraine prevalence and may partially explain the heterogeneity between studies.

Rapid microsatellite development in Gekko japonicus using sequenced restriction-site associated DNA markers.

Twelve polymorphic microsatellite loci were isolated in the Japanese gecko, Gekko japonicus. We genotyped one population from Wenzhou, Zhejiang Province, China (N = 36). The mean number of observed alleles per locus was 7.3 (range 4 to 13). Observed and expected heterozygosity values ranged from 0.200 to 0.944 and from 0.395 to 0.797, respectively. One locus (GJ20) showed significant departure from Hardy-Weinberg equilibrium; no linkage disequilibrium was found between any two loci. These informative microsatellite markers will be useful for population genetic analyses of G. japonicus and other species in the genus Gekko.

Inhibition mechanism of cordycepin and ergosterol from Cordyceps militaris Link. against xanthine oxidase and cyclooxygenase-2.

Cordyceps militaris Link. (C. militaris) is an entomopathogenic fungus that parasitizes the pupa or cocoon of lepidopteran insect larvae, with various bioactive compounds. Cordycepin and ergosterol are the two active components in C. militaris. This study aimed to evaluate the inhibitory activity of cordycepin and ergosterol against xanthine oxidase (XO) and cyclooxygenase-2 (COX-2), as well as investigate the inhibition mechanism. Cordycepin could better inhibit XO (IC50 = 0.014 mg/mL) and COX-2 (IC50 = 0.055 mg/mL) than ergosterol. Additionally, surface hydrophobicity and circular dichroism (CD) spectra results confirmed the conformational changes in enzymes induced by cordycepin and ergosterol. Finally, cordycepin and ergosterol significantly decreased uric acid (UA) and inflammatory factors to normal level in mice with gouty nephropathy (GN). This study could provide theoretical evidence for utilization of C. militaris in hyperuricemia-management functional foods.

Arthroscopic reconstruction of the anterior cruciate ligament with the LARS artificial ligament: thirty-six to fifty-two months follow-up study.

OBJECTIVES: This study aims to analyze the operating methods and fundamental clinical effects of the reconstruction of the anterior cruciate ligament (ACL) with the Ligament Advancement Reinforcement System (LARS) artificial ligaments using an arthroscopy. PATIENTS AND METHODS: Fifty-three patients with ACL rupture who were treated using LARS artificial ligaments were enrolled in this retrospective study. The mean age at the time of reconstruction was 31.2 y (range, 22-51y). Average time from injury to surgery was 18 d (range, 5-51 d). Average follow-up period was 45 mo (range 36-52 months). Follow-up examinations included the Lysholm Knee Score and the International Knee Documentation Committee (IKDC) score. RESULTS: The average Lysholm Knee Score was 53.1±5.8 preoperatively (range, 47-76) versus 93.2±3.4 three years after operation (range, 80-100). Fifty-one of 53 patents (96.2%) showed good or excellent results at final assessment. The final IKDC score 3 years after operation were normal in 28 patients (52.8%), nearly normal in 23 patients (43.4%), and abnormal in 2 patients (3.8%). No postoperative complications, such as infection, ligament rupture, or ligament cinch occurred. CONCLUSIONS: The results suggest that LARS artificial ligament appears to be an effective graft for ACL reconstruction leading to good knee function and stability. Long-term follow-up should be performed to confirm the durable stability of the knee and the tolerance of the knee to the LARS artificial ligament.

Identification and functional characterization of a novel mutation P459H and a rare mutation R483W in the CYP21A2 gene in two Chinese patients with simple virilizing form of congenital adrenal hyperplasia.

BACKGROUND: Steroid 21-hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH). Clinically, 21-OHD is categorized into saltwasting, simple-virilizing (SV), and non-classical (NC) forms. It is well recognized that a good correlation exists between genotype and clinical phenotype of CAH. AIM: The aim of this study was to identify CYP21A2 gene mutations in 2 Chinese patients with SV CAH along with their parents and other family members. STUDY DESIGN AND RESULTS: By direct sequencing the CYP21A2 gene, a novel mutation, P459H, was detected in 1 patient; and a previously described uncharacterized mutation, R483W, was found in another patient. The 21-hydroxylase activities were determined by measuring the converting rate of progesterone to 11-deoxycorticosterone in COS-7 cells overexpressed with these mutated proteins. Our results revealed significantly reduced enzyme activity in both mutants: residual activity of P459H and R483W towards progesterone was 6.8%±2.1 and 2.9%±1.5, respectively compared to that of the wild type. We also demonstrated the loss of 21-hydroxylase activities using a three-dimensional model of CYP21A2. CONCLUSION: Both R483W and P459H mutations are confirmed to be related to NC CAH by in vitro functional study, with phenotype variance of R483W in Tunisian and Chinese patients. This study will aid in predicting disease severity and in facilitating family genetic counseling.

Diaphragm valves reduce gastroesophageal reflux following cardiomyotomy for patients with achalasia.

BACKGROUND: This study was designed to investigate the effect of a novel surgical method on cardia sphincter function and complication rates after Heller's cardiomyotomy for patients with achalasia. METHODS: Forty-eight patients (19 males, mean age 34.0 +/- 10.5 years, range, 12-58) were included in this study. A spindle diaphragm valve was used in the surgery to rebuild the cardiac sphincter function. The efficacy of the surgery was determined by clinical assessment of symptoms and lower esophageal sphincter pressure (LESP) measurements. Barium meal examination was also used to evaluate the efficacy. RESULTS: The mean LESP before surgery was 41.3 +/- 11.6 mmHg. It was reduced to 16.8 +/- 3.7 mmHg and 17.5 +/- 2.5 mmHg 3 and 12 months after surgery (P < 0.01). All patients were free of symptoms such as swallow difficulties or acid reflux during the follow up. However, barium swallow examination showed that 1 patient had mild reflux after the surgery. Clinical symptom scores on swallow difficulties/obstruction was reduced from 2.5 +/- 0.65 before surgery to 0.06 +/- 0.24 12 months after the surgery (P < 0.01). CONCLUSION: A spindle diaphragm valve used with Heller's cardiomyotomy was associated with a very low incidence of post-surgical complications, such as gastroesophageal reflux. This technique may be used in treating all patients with achalasia.