BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.
Animals ; Mice ; Interleukin-10 ; Bifidobacterium breve ; Up-Regulation ; Angiogenesis Inhibitors ; Sunitinib ; X-Ray Microtomography ; Administration, Oral ; Wound Healing ; Antibodies, Neutralizing

Background Heavy metal emissions from mining and smelting areas are a global problem, and health risks associated with heavy metal contamination of soils are of great concern. The long-term mining of the largest realgar mine in Asia has caused severe arsenic and other metal pollution to the surrounding rivers and soils. Objective To understand the levels of metal contamination and health risks in agricultural soils of villages surrounding the largest realgar mine in Asia, and to lay a good foundation for further necessary pollution control actions and decisions. Methods A field survey was conducted to collect soil samples according to the Technical rules for monitoring of environmental quality of farmland soil (NY/T 395-2012), and then inductively coupled plasma mass spectrometry was used to determine the contents of 28 heavy metals [cadmium (Cd), arsenic (As), lead (Pb), mercury (Hg), chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), beryllium (Be), selenium (Se), cobalt (Co), antimony (Sb), molybdenum (Mo), vanadium (V), barium (Ba), thallium (Tl), boron (B) , bismuth (Bi), lithium (Li), manganese (Mn), strontium (Sr), calcium (Ca), rubidium (Rb), iron (Fe), magnesium (Mg), aluminum (Al), kalium (K), and titanium (Ti)]. Geoaccumulation index, single factor pollution index, and Nemerow comprehensive index were used to evaluate the degree and characteristics of single metal pollution and combined pollution in soil, respectively. A health risk assessment model was used to evaluate the risks of metals in soil to human health. Results The results of geoaccumulation index calculation revealed that 22 heavy metals were enriched in the soil, and the indexes of target heavy metals from high to low were Cd > Se > Pb >Hg > As > Co> Ni > Cu > Zn > Bi > Sb > Mo > Be> Cr > Ba >V > Li > Sr> Mn> Rb > Ca> Tl . The single factor pollution indexes of 17 heavy metals from high to low were Be > Cd > B > Mo > V > As > Ni > Cu > Pb > Zn > Co > Se > Tl > Ba > Cr > Hg > Sb. The Nemerow comprehensive index indicated all sampling points were graded as severe pollution. The mean of total non-carcinogenic health risk values and the mean of carcinogenic health risk values for the target heavy metals in the area were higher than the threshold (1) and the maximum acceptable risk (1.0×10^–4), respectively. The total carcinogenic health risks for adults and children reached 1.1×10^–3 and 1.67×10^–3, respectively. The mean non-carcinogenic health risk values of As, Co, Cr, and Pb pollution were greater than 1, and the maximum non-cancer risk value of Sb for children was greater than 1. The mean carcinogenic risk values of Ni, As, and Cu exceeded 1.0×10^–4 for both adults and children, and the maximum carcinogenic risk values of Be and Cr for children were more than 1.0×10^–4. Conclusion The farmland soil around the hugest realgar mine in Asia is contaminated by multiple metals. The study soil is seriously polluted by Cd, Se, Pb, As, Hg, Be, B, Mo, V, Ni, Cu, Pb, Zn, Co, and Ba. The pollution of Ni, As, Cu, Cr, and Be is considered as carcinogenic hazards to health, while the pollution of As, Co, Cr, Pb, and Sb poses non-carcinogenic health risks. Our study findings show that the soil is polluted by Co and Group 1 carcinogen Be, which could cause health risks; although Cr and Sb have not reached severe pollution levels, there are certain health risks and also need attention.

RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers. However, efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging. Recently, more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating. Due to the flexibility and deformability of nucleic acids, the nanoassemblies could be fabricated with different shapes and structures. With hybridization, nucleic acid nanoassemblies, including DNA and RNA nanostructures, can be applied to enhance RNA therapeutics and diagnosis. This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.

OBJECTIVE: To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS). METHODS: A child who was diagnosed with SBCS in June 2017 at Henan Children's Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members. RESULTS: The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c.4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing. CONCLUSION The c.4073-2A>G splicing variant of the CHD3 gene probably underlay the SBCS in this patient.
DNA Copy Number Variations ; Heterozygote ; Pedigree ; Phenotype ; RNA Splicing ; Mutation

Objective: Effective prevention and control measures are essential to contain outbreaks of infectious diseases, such as coronavirus disease (COVID-19). Understanding the characteristics of case clusters can contribute to determining which prevention and control measures are needed. This study describes the characteristics of COVID-19 case clusters in Malaysia, the method used to detect a cluster’s index case and the mode of early transmission, using the seven cluster categories applied in Malaysia. Methods: This cross-sectional study collected publicly available data on COVID-19 clusters occurring in Malaysia from 1 March 2020 to 31 May 2021. The characteristics of cases were described by category, and their associations with several outcomes were analysed. Descriptive analyses were performed to explore the method used to detect the index case and the mode of early transmission, according to cluster category. Results: A total of 2188 clusters were identified. The workplace cluster category had the largest proportion of clusters (51.5%, 1126/2188 clusters), while the custodial settings category had the largest median cluster size (178 cases per cluster) and longest median duration of cluster (51 days). The high-risk groups category had the highest mortality. There were significant differences in cluster size, duration and rate of detection across the categories. Targeted screening was most commonly used to detect index cases, especially in custodial settings, and in imported and workplace clusters. Household–social and social–workplace contacts were the most common modes of early transmission across most categories. Discussion: Targeted screening might effectively reduce the size and duration of COVID-19 clusters. Measures to prevent and control COVID-19 outbreaks should be continually adjusted based on ongoing assessments of the unique context of each cluster.

Grey literature is a valuable source of information for evidence synthesis in public health, particularly when swift action is needed to address issues. In 2020, the COVID-19 pandemic was an example where rapid knowledge sharing was quintessential as the world grappled with the management of a novel coronavirus that was spreading at an alarming rate. To document and contextualise the health systems strategies used to address the COVID-19 pandemic in Malaysia from January 2020 to April 2020, we conducted a rapid review of publicly available documents from WHO Global Research on Coronavirus Disease (COVID-19) (WHO database), official government websites and local newspapers. This paper aims to describe the methods and discuss the lessons learnt from the review. In the early stage of the pandemic, published articles in the WHO database focused on clinical knowledge, hence we relied on grey literature as a primary source of information, mainly official government websites, which provided real-time information relevant to our study. Grey literature can be a good source of information for a rapid review of nascent and urgent topics particularly in the area of public health, however, a trade-off between comprehensiveness and efficiency has to be considered.
Gray Literature

Objective:To explore the clinical value of modified upper urinary tract video urodynamics in evaluating the surgical effect and guiding the follow-up treatment after ureteral reconstruction.Methods:From December 2018 to November 2020, sixty-nine patients underwent upper urinary tract reconstruction and received modified video urodynamics at the time of nephrostomy removal 3 months after the surgery in the RECUTTER database (29 cases in Peking University First Hospital, 22 cases in Emergency General Hospital, and 18 cases in Beijing Jiangong Hospital). There were 39 males and 30 females, with an average age of (40.4±12.7)years. The stricture was located in left in 34 patients, right side in 27 patients, and bilateral sides in 8 patients. The upper, middle, and lower thirds of the ureter were affected in 26, 10, and 33 cases, respectively. The preoperative creatinine was (92.3±26.9)μmol/L, and the estimated glomerular filtration rate (eGFR) was (85.1±23.2)ml/(min·1.73m 2). The upper urinary tract reconstruction included ileal replacement of ureter in 25 cases (36.2%), pyeloplasty in 8 cases (11.6%), ureteroneocystostomy in 9 cases (13.0%), boari flap in 6 cases (8.7%), lingual mucosal graft ureteroplasty in 9 cases (13.0%), appendiceal onlay ureteroplasty in 3 cases (4.3%), ureteroureterostomy in 3 cases (4.3%), and balloon dilation in 6 cases (8.7%). Based on the pressure and imaging, the results could be divided into three types, type Ⅰ, the pressure difference remained stable near baseline, and the renal pelvis pressure was below 22 cmH 2O(1 cmH 2O=0.098 kPa), and the reconstructed ureter is well visualized during the whole perfusion process; type Ⅱ, the pressure difference increases with the perfusion, but it can decrease to a normal level with the ureteral peristalsis; type Ⅲ, the pressure difference exceeds 15 cmH 2O, and the ureteral peristalsis is weak or disappears at the same time. The management strategies and treatment effects of different subtypes were analyzed. Successful treatment was defined as no further treatment required, the absence of hydronephrosis-related symptoms, and the improved or stabilized degree of hydronephrosis. Results:All 69 patients successfully completed upper urinary tract video urodynamics. The pressure difference was higher than 15 cmH 2O in 8 patients, and the median pressure difference was 37(19-54)cmH 2O. The renal pelvis pressure exceeded 22 cmH 2O in 10 patients, and the median pressure was 63.5 (24-155) cmH 2O. Video urodynamic results of upper urinary tract were classified as type Ⅰ in 60 cases, type Ⅱ in 5 cases, and type Ⅲ in 4 cases. Patients in type Ⅰ do not require other treatment after nephrostomy tube removal. Patients in type Ⅱ should avoid holding urine after the removal of nephrostomy and D-J tubes. All patients in type Ⅲ received further treatment, of which 2 patients replaced D-J tube regularly, 1 patient underwent long-term metal ureteral stent replacement, and 1 patient underwent ureteroscopic balloon dilation. The median follow-up time was 24 (18-42) months. All patients in type Ⅰ met the criteria for surgical success, The pre-and postoperative creatinine in type Ⅰ patients were (88.71±23.09)μmol/L and (88.75±23.64)μmol/L ( P=0.984), and eGFR were (88.06±22.66)ml/(min· 1.73m 2)and (87.97±23.01)ml/(min·1.73m 2), respectively( P=0.969). For type Ⅱ patients, ultrasound showed that the degree of hydronephrosis improved in 3 cases and remained stable in 2 cases. The pre-and postoperative creatinine were (105.97±7.75)μmol/L and (97.63±7.56)μmol/L ( P=0.216), and eGFR were (69.08±14.74)ml/(min·1.73m 2)and (75.95±14.02)ml/(min·1.73m 2)( P=0.243), respectively. For type Ⅲ patients, ultrasound showed that the degree of hydronephrosis remained stable. The pre-and postoperative creatinine were (105.14±44.34)μmol/L and (101.49±57.02)μmol/L ( P=0.684), and eGFR were (65.32±19.85)ml/(min·1.73m 2) and (73.42±27.88) ml/(min·1.73m 2), respectively( P=0.316). Conclusions:The pressure and imaging results of modified upper urinary tract video urodynamics can assist in evaluating the surgical effect of ureteral reconstruction, and the classification has certain guiding significance for further treatment.

OBJECTIVE：To investigate the inhibitory effects of total alkaloids of Gelsemium elegans （TAG） on the proliferation and angiogenesis of human colon cancer cells. METHODS ：Human colon cancer cell line HT- 29 and HUVEC were cultured in vitro . After the intervention of low- ，medium-，high-dose TAG （40，80，120 μg/mL），the morphology of the two cells was observed by fluorescence inversion microscope. The survival rate of HT- 29 cells and HUVEC was detected by CCK- 8 assay. Flow cytometry was used to detect HT- 29 cell cycle. The migration rate ，invasion rate and tube number of HUVEC were observed by scratching test ，Transwell invasion experiment and tube formation experiment. RESULTS ：Compared with blank group ，HT-29 cells and HUVEC were decreased to different extents in TAG groups ；dead cells were observed ，and the survival rate of both decreased significantly （P＜0.05 or P＜0.01）. The proportion of HT- 29 cells at G 2/M phase in TAG groups as well as those at G 0/G1 phase in medium-dose group were increased significantly ；the proportion of HT- 29 cells at S phase in TAG groups as well as those at G 0/G1 phase in high-dose group were decreased significantly （P＜0.05 or P＜0.01）. Survival rate ，migration rate and invasion rate of HUVEC were decreased significantly in TAG groups ，and tube number was also decreased significantly at each time point during 4-24 h（P＜0.01）. CONCLUSIONS ：TAG have inhibitory effect on the proliferation of human colon cancer HT- 29 cells and HUVEC，can change HT- 29 cell cycle ，inhibit the migration ，invasion and tube formation of HUVEC.

Objective: To investigate the prognosis and influencing factors of postoperative low anterior resection syndrome (LARS) for rectal cancer patients undergoing laparoscopic sphincter-preserving radical resection. Methods: A retrospective case-control study was used in this study. Clinical data of 268 rectal cancer patients undergoing laparoscopic sphincter-preserving radical resection at Department of Gastrointestinal Surgery of The First Affiliated Hospital of Bengbu Medical College from January 2016 to January 2018 were retrospectively collected. Inclusion criteria: (1) operation procedure was total mesorectal excision (TME) and sphincter-preserving radical resection; (2) rectal cancer was confirmed by postoperative pathology; (3) age of patient was ≥ 18 years old. Exclusion criteria: (1) patient who had history of pelvic surgery and pelvic fractures, which would affect the anorectal function; (2) patient who had history of preoperative chronic constipation and irritable bowel syndrome, which would affect defecation; (3) patient who developed postoperative complications, such as anastomotic leakage, which would affect defecation function; (4) patient who received long-term use of drugs, which would affect the function of gastrointestinal tract or anus; (5) patient suffered from mental illness, who was unable to communicate properly; (6) patient who was lack of clinical data or had incomplete clinical data. Patients were followed up at 3, 6 and 12 months postoperatively, and LARS was diagnosed and graded according to the LARS score scale. The LARS score ranged from 0 to 42 points, and 0 to 20 was difined as no LARS, 21 to 29 was mild LARS, and 30 to 42 was severe LARS. LARS score >20 points at any time point was defined as postoperative LARS. Severe LARS transferring into mild LARS and mild LARS transferring into no LARS was defined as symptom improvement. Incidence and outcomes of LARS were evaluated. The factors associated with LARS outcomes were analyzed using χ² test and logistic regression model. Results: A total of 268 patients were enrolled. The incidence of LARS was 42.9% (115/268), 32.5% (87/268) and 20.1% (54/268) at 3, 6, and 12 months postoperatively respectively, and no new case of LARS was found after 3 months postoperatively. The incidence of mild LARS was 25.7% (69/268), 17.2% (46/268) and 8.6% (23/268) at 3, 6, and 12 months postoperatively respectively, and mild LARS incidence at 6 months was significantly lower than that at 3 months (χ²=5.857, P=0.016), and was significantly higher than that at 12 months (χ²=8.799, P=0.003). The incidence of severe LARS was 17.2% (46/268), 15.3% (41/268) and 11.6% (31/268) at 3, 6, and 12 months postoperatively respectively, without significant difference among 3 time points (all P>0.05). The improvement rate within one year after surgery in patients with mild LARS diagnosed at 3 months was significantly higher than that in patients with severe LARS (88.4% vs. 32.6%, χ²=38.340, P<0.001). Univariate analysis showed that female, distance from anastomosis to anal verge < 5 cm and tumor diameter ≥ 5 cm were associated with unsatisfied LARS outcomes (all P<0.05). Logistic regression analysis showed that distance from anastomosis to anal verge <5 cm was an independent risk factor for LARS outcome (OR=3.589, 95% CI: 1.163 to 2.198, P<0.001). Conclusions The incidence of LARS after laparoscopic sphincter-preserving radical resection decreases with time. The improvement rate within postoperative 1-year of severe LARS is lower than that of mild LARS. Low anastomotic position may lead to impaired improvement of LARS.