Objective:To compare the efficacy and safety of robotic surgery and open surgery in the treatment of hilar cholangiocarcinoma.Methods:PubMed, Embase, Cochrane Library, Web of Science, CNKI and Wanfang database were searched to compare the treatment of hilar cholangiocarcinoma by robotic surgery and traditional open surgery. Literatures were searched from the establishment of the database to July 2023. Compare operation time, intraoperative blood transfusion rate, R 0 resection rate, lymph node metastasis rate, postoperative complication rate and hospital stays between the two groups. The combined odds ratio ( OR) and mean difference ( MD) and 95% confidence interval (95% CI) were calculated using RevMan 5.4 software. Results:A total of 4 studies were included, including 267 patients with hilar cholangiocarcinoma. There were 177 males and 90 females, aged (58.8±5.7) years. A total of 267 patients were divided into open surgery group ( n=165) and robotic surgery group ( n=102) according to the surgical formula. The extract results show: operative time ( MD=-103.96, 95% CI: -216.90-8.98, P=0.070) and intraoperative blood transfusion rate ( OR=1.32, 95% CI: 0.43-4.07, P=0.630), R 0 resection rate ( OR=1.41, 95% CI: 0.71-2.81, P=0.330), lymph node metastasis rate ( OR=1.62, 95% CI: 0.46-5.63, P=0.450), postoperative complications ( OR=0.60, 95% CI: 0.28-1.31, P=0.200), and postoperative hospital stay ( MD=2.17, 95% CI: -11.56-15.90, P=0.760). Conclusion:In the treatment of hilar cholangiocarcinoma, robotic surgery is as safe and feasible as open surgery. However, due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

Objective To evaluate the bioequivalence of two formulations of minocycline hydrochloride capsules administered orally after fasting administration and fed administration.Methods An open-label,randomized,two-period,self-crossover design was employed to assess the bioequivalence study.Twenty-eight healthy subjects were enrolled in both fasting and fed groups,with each period involving a single administration of either the reference formulation or the test formulation of 50 mg,separated by a washout period of 7 days.The concentration of minocycline in human plasma was determined by HPLC-MS/MS and was used for calculating pharmacokinetic parameters and evaluating the bioequivalence of the test formulation and reference formulation.Results After oral administration of test and reference formulations of minocycline under fasting condition,the Cmax Values of minocycline were(541±137)ng·mL-1 for the test formulation and(558±140)ng·mL-1for the reference formulation.The AUC0-t values were(8 347±1 986)h·ng·mL-1 for the test and(8 205±1 790)h·ng·mL-1 for the reference.The t1/2 values were(18.2±2.84)h for the test and(18.0±3.05)h for the reference.After oral administration of the test and reference formulations of minocycline under fed condition,the Cmax values of minocycline were(349±72.1)ng·mL-1 for the test and(352±73.2)ng·mL-1for the reference.The AUC0-twere(6 428±1 077)h·ng·mL-1 for the test and(6 588±1 118)h·ng·mL-1 for the reference.The t1/2values were(18.5±3.10)h for the test and(18.4±3.21)h for the reference.Under fasting condition,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test and reference formulations were(90.84%,101.46% ),(95.2%,102.8% ),and(95.31%,102.71% ),respectively.Under fed conditions,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test formulation and the reference formulation were(94.71%,103.42% ),(95.40%,99.83% ),and(95.79%,100.02% ),respectively.Conclusions Bioequivalence of the two minocycline formulations was demonstrated after fasting administration and fed administration in a healthy Chinese population.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

Objective To evaluate the effect of different techniques of hepatic artery reconstruction on postoperative hepatic artery complications and clinical prognosis in liver transplantation. Methods Clinical data of 140 liver transplant recipients were retrospectively analyzed. All recipients were divided into the conventional hepatic artery reconstruction group (n=123) and special hepatic artery reconstruction group (n=17) according to hepatic artery reconstruction methods. Intraoperative and postoperative clinical indexes, the incidence of postoperative hepatic artery complications and survival rate were compared between two groups. Results The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at postoperative 1 d, total bilirubin (TB) at postoperative 7 d and prothrombin time international normalized ratio (PT-INR) at postoperative 30 d in special hepatic artery reconstruction group were higher than those in conventional hepatic artery reconstruction group, and the differences were statistically significant (all P < 0.05). There were no significant differences in the operation time, anhepatic phase, intraoperative blood loss, intraoperative transfusion volume of red blood cells, cold or warm ischemia time, the length of intensive care unit (ICU) stay, the length of hospital stay and postoperative blood flow of liver allograft between two groups (all P > 0.05). In the conventional hepatic artery reconstruction group, 5 recipients developed hepatic artery complications, whereas no hepatic artery complications occurred in the special hepatic artery reconstruction group, with no significant difference between two groups (P > 0.05). In the special hepatic artery reconstruction group, the 1-, 3- and 5-year cumulative survival rates were equally 82.4%, compared with 85.0%, 78.9% and 75.6% in the conventional hepatic artery reconstruction group, respectively. There was no significant difference between two groups (all P > 0.05). Conclusions When hepatic artery variations and (or) lesions are detected in donors and recipients, use of special hepatic artery reconstruction may effectively restore the hepatic arterial blood flow of liver allograft after liver transplantation, and will not affect the incidence of hepatic artery complications and survival rate of the recipients following liver transplantation.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Objective: To understand the relationships of social exclusion, personality trait and emotion regulation with willingness to seek help after being bullied, and to provide reference for rationalized intervention of campus bullying among middle school students. Methods: A tatal of 2 040 middle school students from a middle school in Jiangxi Province were selected as the research objects, and surveyed by general situation questionnaire, Olweus Bullying Questionnaire, Willingness to Seek Help Scale, social exclusion scale, personality scale and Emotion Regulation Scale. Among them, a further survey of 381 bullies was conducted and SPSS 26.0 was used for statistical processing of data. Results: About 55.88% (133/238) and 58.74% (84/143) reported willingness to seek help after being bullied among middle and high school students, respectively( χ 2=0.30, P >0.05). There were no significant differences in gender and residency( P >0.05). In junior middle school students, compared with the non help willingness group( 3.83± 0.78，3.35±1.03，3.33±1.03，29.81±7.77), the rejected scores of the help willingness group were lower(3.57±0.75), scores of affinity and openness in personality traits were higher(3.69±0.88，3.72±0.79), the cognitive reappraisal scores were higher( 32.42 ±8.25). Among senior middle school students, the rejected and expression suppression scores of the help willingness group were lower(3.51±0.67，26.96±7.47), while extroversion personality traits were higher(3.61±0.95). Multivariate unconditional Log binomial regression analysis showed that high score of expression suppression was associated with less willingness to seek help( OR=0.94, P =0.02). Conclusion Social exclusion, personality trait and emotional regulation may have certain influences on willingness to seek help after being bullied among junior and senior middle school students, effects varies by grade level.

OBJECTIVE：To establi sh the quality standard of Yao medicine Pileostegia tomentella，and to provide reference for its quality control. METHODS ：Totally 10 batches of P. tomentella were collected from Guangxi area. The properties of P. tomentella were observed and microscopic identification was conducted for the transverse section of its stems ，roots and powder. TLC method was established by using 7-hydroxycoumarin as reference. The contents of water ，total ash ，acid-insoluble ash and alcohol-soluble extract in P. tomentella were determined. The contents of skimmin ，7-hydroxycoumarin and 7-hydroxy-8- methoxycoumarin in P. tomentella were determined by HPLC. RESULTS ：The root and stem surface of P. tomentella possessed obvious wrinkles ，hard texture ，slight smell and bitter taste ，and there were secretory cells and needle crystal cells in the cross section. The medicinal powder contained calcium oxalate needle crystal ，calcium oxalate square crystal ，sclerotic cell and starch granules. The results of TLC showed that the spots of the same color were found in the corresponding positions of chromatograms of test samples and 7-hydroxycoumarin control. In the 10 batch of P. tomentella ，the contents of water were 9.1％-11.8％；those of total ash were 3.6％-6.7％；those of acid-insoluble ash were 0.10％-0.44％；those of alcohol-soluble extract were 8.9％-14.0％.The linear range of skimmin ，7-hydroxycoumarin and 7-hydroxy-8-methoxycoumarin were 6.088-182.640，1.568-47.040 and 1.096- 32.880 μg/mL（all r not less than 0.999 7）. The average recoveries were 99.47％，101.07％ and 99.89％（RSD were all less than 2％）. RSDs of precision ，stability（24 h），reproducibility and durability tests were all lower than 2％ . The contents of 3 components such as skimmin were 1.337-9.534，0.348-2.236， 0.083-1.088 mg/g，respectively. CONCLUSIONS ：It is preli- 201705） minarily proposed that the content of water in P. tomentella is not more than 12.0％ ；that of total ash is not more than 7.0％；that of alcohol-soluble extract is not less than 8.0％； E-mail：luguoshou@foxmail.com that of ski mmin is not less than 1.30 mg/g；that of 7-hydroxy- coumarin is not less than 0.30 mg/g；that of 7-hydroxy-8-methoxycoumarin is not less than 0.06 mg/g.

Objective:To observe the clinical effect of four-point fixation in patients with posterior chamber intraocular lens dislocation.Methods:A retrospective case series study was adopted.Sixteen patients (16 eyes) with posterior chamber intraocular lens dislocation who underwent suture suspension techniques with four-point fixation in Changzhou No.2 people's Hospital from January 2015 to January 2018 were enrolled.Postoperative effects were observed during follow-up, ranging from 6 to 13 months.The preoperative and 6-month postoperative uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), corneal endothelium cell count and astigmatism were measured and the differences were compared, and the relationships between total astigmatism and corneal astigmatism or intraocular lens induced astigmatism were analyzed, and the postoperative position of intraocular lens and complications were observed.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Changzhou No.2 People's Hospital (No.2015-C-012-01).Written informed consent was obtained from each patient before surgery.Results:The mean preoperative UCVA (LogMAR) and BCVA (LogMAR) were 1.09±0.24 and 0.48±0.20, respectively, which were significantly improved to 0.30±0.12 and 0.26±0.13 at 6 months after operation, respectively.And the differences were statistically significant ( t=11.782, 3.795; both at P<0.01).The preoperative and 6-month postoperative corneal endothelium cell count were (2 270±360)/mm 2 and (2 032±327)/mm 2, respectively, and the difference was not significant ( t=1.921, P=0.074).The 6-month postoperative mean total astigmatism, corneal astigmatism and intraocular lens induced astigmatism were (-1.47±0.82)D, (-1.34±0.61)D and (-0.22±0.35)D, respectively.There was a highly positive correlation between total astigmatism and corneal astigmatism ( r=0.885, P<0.05), but there was no significant correlation between total astigmatism and intraocular lens induced astigmatism ( r=-0.432, P=0.095).No dislocation, deviation or torsion of intraocular lens were observed during the follow-up.Varying degree of symptoms of iridocyclitis were observed during early stage after operation, which disappeared after treatment.There were two cases of high intraocular pressure, which were normal after treatment.No retinal detachment, choroidal detachment, expulsive suprachoroidal hemorrhage, endophthalmitis, corneal endothelial decompensation or other complications occurred during and after operation. Conclusions:There is a stable position of intraocular lens, good visual acuity and few complications after four-point fixation with suture and suspension, which is a feasible method to treat dislocated intraocular lens.

Objective:To investigate the influence of high frequency oscillatory ventilation combined with ulinastatin on serum inflammatory factors, blood gas indexes and endothelial function in patients with respiratory distress after smoke inhalation lung injury.Methods:Sixty-two patients with acute respiratory distress syndrome induced by smoke inhalation lung injury from January 2016 to January 2019 in the 910th Hospital of the PLA Joint Service Support Unit were enrolled.With a prospective cohort study, the patients were divided into control group (31 cases) and observation group (31 cases) according to the random number table.The control group were treated with high-frequency oscillatory ventilation.The observation group was given intravenous ulinastatin treatment on the basis of the control group, 3×105 U/time, dissolved in 50 ml of normal saline, once every 8 hours.Acute physiology and chronic health evaluation (APACHE) Ⅱ score was performed before intervention and 48 hours after intervention.Serum interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α(TNF-α), nitric oxide, endothelin-1 were detected by enzyme-linked immunosorbent assay. Arterial blood oxygen partial pressure (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2), oxygenation index were measured by blood gas analyzer. The Extra-vascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI) were recorded by pulse indicator continuous cardiac output monitoring.The occurrence of adverse reactions were recorded. Results:The IL-6 ((66.8±15.2) ng/L), IL-8 ((70.3±10.4) ng/L, TNF-α ((24.6±3.5) ng/L) of the observation group after treatment 48 hours were lower than before treatment ((89.3±21.0) ng/L, (288.4±33.5) ng/L, (101.3±9.0) ng/L), the difference was statistically significant(t value was 5.704, 21.215, 30.281, repectively, all P<0.05), and the observation group were significantly lower than the control group((90.4±22.4) ng/L, (162.4±16.6) ng/L, (62.3±4.4) ng/L), the difference was statistically significant(t value was 4.906, 12.324, 19.252, repectively, all P<0.05). After 48 h of intervention in the control group and the observation group after 48 h of intervention, the oxygenation index ((208.5±55.4) mmHg and (315.3±49.8) mmHg), PaO 2 ((101.6±12.4) mmHg and (118.8±10.3) mmHg) of the control group and the observation group after 48 hours of intervention were significantly higher than before intervention((114.8±24.6) mmHg and(112.3±20.5) mmHg, (70.6±10.5) mmHg and(70.3±10.2) mmHg)(t value was 15.663 and 22.387, 11.216 and 16.214, repectively, all P<0.05, the PaCO 2 ((44.7±7.4) mmHg and (39.3±4.8) mmHg), EVLWI ((12.42±3.66) ml/kg and (9.70±2.33) ml/kg), PVPI (2.34±0.48 and 1.82±0.35) significantly lower than before intervention((47.8±5.6) mmHg and(48.3±6.5) mmHg, (16.58±4.05) ml/kg and (16.60±4.10) ml/kg, 2.86±0.55 and 2.90±0.53), ( t value was 3.655 and 7.372, 3.516 and 6.521, 3.571 and 8.024, repectively, all P<0.05), the oxygenation index , PaO 2 in the observation group after intervention were significantly higher than those in the control group, P<0.05, while PaCO 2, EVLWI and PVPI in the observation group were significantly lower than the control group, t value was 7.106, 4.213, 4.037, 7.122, 3.976, repectively, all P<0.05.The nitric oxide((76.65±30.25) μmol/L and (54.15±20.36) μmol/L), endothelin ((58.32±20.26) ng/L and (42.23±21.15) ng/L), APACHE Ⅱ score ((10.05±2.84) points and (7.14±2.74) points) of the control group and the observation group after 48 h intervention were significantly lower than before intervention ((90.30±33.33) μmol/L and(89.62±34.64) μmol/L, (71.64±28.35)ng/L and (70.36±26.56)ng/L, (23.46±4.13)points and(23.60±4.20)points), ( t value was 3.761 and 8.063, 4.031 and 7.376, 6.193 and 11.531, repectively, all P<0.05). The nitric oxide, The endothelin and APACHE Ⅱ scores in observation group after 48 h intervention were significantly lower than those of the control group ( t value was 3.759, 3.515, 3.715, repectively, all P<0.05). There were no adverse drug reactions occurred during the treatment in both groups. Conclusion:High frequency oscillatory ventilation combined with ulinastatin in the treatment of respiratory distress after smoke inhalation lung injury can inhibit the excessive release of inflammatory mediators and improve vascular endothelial function, thereby reducing capillary leakage, reducing EVLWI and increasing oxygenation index.

Objective:To study the significance of H19 gene in the progress from normal mucosa through oral submucous fibrosis (OSF) to carcinogenesis.Methods:Real-time fluorescent quantitative PCR technique was used to detect LncRNA H19 expression level in 12 cases of normal buccal mucosa tissue,33 cases of OSF buccal mucosa tissue and 31 cases of buccal carcinoma with OSF.Results:The relative expression levels of LncRNA H19 in normal buccal mucosa tissues,OSF buccal mucosa tissue and buccal carcinoma with OSF tissue were 1.17 ±0.37,3.44 ± 1.08 and 8.88 ± 1.78 respectively(between each 2 groups,P ＜ 0.01).Conclusion:H19 may involve the occurrence and canceration of OSF.