Transanal drainage tube for prevention of anastomotic leak after anterior resection for rectal cancer: a meta-analysis / 中华胃肠外科杂志

Objective: To assess the effectiveness of transanal drainage tube (TDT) in reducing the incidence of anastomotic leak following anterior resection in patients with rectal cancer. Methods: We conducted a systematic search for relevant studies published from inception to October 2022 across multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. Meta-analysis was performed using Review Manager 5.4 software. The primary outcomes included total incidence of anastomotic leak, grade B and C anastomotic leak rates, reoperation rate, anastomotic bleeding rate, and overall complication rate. Results: Three randomized controlled trials involving 1115 patients (559 patients in the TDT group and 556 in the non-TDT group) were included. Meta-analysis showed that the total incidences of anastomotic leak and of grade B anastomotic leak were 5.5% (31/559) and 4.5% (25/559), respectively, in the TDT group and 7.9% (44/556) and 3.8% (21/556), respectively, in the non-TDT group. These differences are not statistically significant (P=0.120, P=0.560, respectively). Compared with the non-TDT group, the TDT group had a lower incidence of grade C anastomotic leak (1.6% [7/559] vs. 4.5% [25/556]) and reoperation rate (0.9% [5/559] vs. 4.3% [24/556]), but a higher incidence of anastomotic bleeding (8.2% [23/279] vs. 3.6% [10/276]). These differences were statistically significant (P=0.003, P=0.001, P=0.030, respectively). The overall complication rate was 26.5%(74/279) in the TDT group and 27.2% (75/276) in the non-TDT group. These differences are not statistically significant (P=0.860). Conclusions: TDT did not significantly reduce the total incidence of anastomotic leak but may have potential clinical benefits in preventing grade C anastomotic leak. Notably, placement of TDT may increase the anastomotic bleeding rate.

Effect of miR-96-5p targeting IRS1 on apoptosis of PC12 cells induced by aluminum maltol / 中华劳动卫生职业病杂志

Objective: To investigate the effect and mechanism of miR-96-5p on apoptosis of PC12 cells induced by maltol aluminum. Methods: In January 2021, PC12 cells at logarithmic growth phase were divided into blank control group and low, medium and high dose group. Cells in each group were treated with 0, 100, 200 and 400 μmol/L maltol aluminum for 24 hours respectively. Cells were collected and cell apoptosis rates were detected by flow cytometry, miR-96-5p and insulin receptor substrate 1 (IRS1) mRNA expressions were detected by qRT-PCR, and the protein expression levels of cysteine protease 3 (Caspase3) 、activated cysteine protease 3 (Cleaved-caspase3) 、IRS1、phosphorylated protein kinase B (p-AKT) and phosphorylated glucose synthesis kinase 3β (p-GSK3β) were detected by western blotting. The target binding relationship between miR-96-5p and IRS1 was detected by double luciferase reporter gene experiment. The miR-96-5p inhibitor cells and negative control cells were constructed after transfecting PC12 cells with miR-96-5p inhibitor for 24 hours. The cells were divided into blank control group, negative control group, aluminum exposure group, aluminum exposure+negative control group, aluminum exposure+miR-96-5p inhibition group, and miR-96-5p inhibition group. After transfecting PC12 cells with miR-96-5p inhibition and IRS1 siRNA for 24 h, the cells were divided into aluminum exposure+miR-96-5p inhibition+negative control group and aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group. The control group was cultured in complete culture medium, and cells in the aluminum exposure group were treated with 200 μmol/L maltol aluminum for 24 hours. Cells in each group were collected and the apoptosis rate, miR-96-5p and IRS1 mRNA expression levels, as well as protein expression levels of Caspase3, Cleaved-caspase3, IRS1, p-AKT, and p-GSK3β were measured. Results: After 24 hours of exposure, compared with blank control group and low-dose group, the apoptosis rates, relative expressions of Caspase3 and Cleaved-caspase3 proteins, and relative expressions of miR-96-5p in the medium and high-dose groups of PC12 cells were significantly increased, while the relative expression levels of IRS1 mRNA, IRS1, p-AKT and p-GSK3β proteins were significantly decreased (P<0.05). Targetscan prediction and double luciferase report experiment both proved that IRS1 was a direct target gene of miR-96-5p. In the transfection experiment, compared with the aluminum exposure group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins, the relative expression of miR-96-5p in the aluminum exposure+miR-96-5p inhibition group were significantly decreased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3β proteins were significantly increased (P<0.05). In the IRS1 low expression experiment, compared with the aluminum exposure+miR-96-5p inhibition+negative control group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins in the aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group were significantly increased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3β proteins were significantly decreased (P<0.05) . Conclusion: The increased expression of miR-96-5p and the targeted inhibition of IRS1 may be one of the mechanisms of apoptosis of PC12 cells induced by maltol aluminum exposure.

Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

Short-term efficacy of empagliflozin in children with glycogen storage disease type Ⅰb / 中华儿科杂志

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.

Pathological significance of plasma cell infiltration in diagnosing lymph node diseases / 中华病理学杂志

Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.

Investigation of familial tendency of endometriosis / 中华妇产科杂志

Objective: To investigate the familial heritability of endometriosis and to compare the clinical characteristics of patients with or without a family history of endometriosis. Methods: From January 2020 to June 2022, 850 patients with endometriosis confirmed by laparotomy or laparoscopy in Peking University Third Hospital were included in this study. Clinical data were collected, family history was followed up, and the differences of clinical indicators between patients with and without family history of endometriosis were compared. Results: A total of 850 patients were enrolled, with an average age of (33.8±7.0) years old, 315 (37.1%, 315/850) patients in stage Ⅲ and 496 (58.4%, 496/850) patients in stage Ⅳ. There were 100 patients with family history of endometriosis, accounting for 11.8% (100/850). Most of the 113 relatives involved were mothers, daughters and sisters (76.1%, 86/113), 81.5% (22/27) of the second and third degree relatives were maternal relatives. The median ages of patients with and without family history of endometriosis were 30 and 33 years old respectively at the time of diagnosis. The unmarried rate of patients with family history was higher [42.0% (42/100) vs 26.3% (197/750)]. The percentage of dysmenorrhea patients with family history was higher [89.0% (89/100) vs 55.5% (416/750)]. The medians of dysmenorrhea score in patients with and without family history were 6 and 2, and the median durations of dysmenorrhea were 10 and 1 years. There were significant differences in age, marital status, percentage of dysmenorrhea, dysmenorrhea score and duration (all P<0.001). The median levels of serum cancer antigen (CA) 125 in patients with family history and patients without family history at the time of diagnosis were 57.5 and 46.9 kU/L respectively, with a statistically significant difference (P<0.05). However, there were no significant differences between the two groups in nationality, bady mass index, menarche age, menstrual cycle, menstrual period, menstrual volume, serum CA19-9 level, cyst location and size, stage, history of adverse pregnancy and childbirth, infertility, adenomyosis and deep infiltrating endometriosis (all P>0.05). By comparing the specific conditions of dysmenorrhea patients with and without family history of endometriosis, there were no significant differences between the two groups in terms of the age of onset of dysmenorrhea, duration of dysmenorrhea, primary and secondary dysmenorrhea, and progressive aggravation of dysmenorrhea (all P>0.05). The difference in the degree of dysmenorrhea in dysmenorrhea patients with family history of endometriosis was significant (P<0.001). Conclusions: The incidence of endometriosis has a familial tendency, and most of the involved relatives are the first degree relatives. Compared with patients without family history of endometriosis, endometriosis patients with family history are diagnosed at an earlier age, with higher percentage of dysmenorrhea, had more severe dysmenorrhea and higher serum CA125 level.

Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients / 中华预防医学杂志

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

Persistence follow-up of immune memory to hepatitis B vaccine among infants with non- and low-response to primary vaccination after revaccination with three doses / 中华预防医学杂志

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95%CI: 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.82 (0.18-1.46) (P=0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.78 (0.18-1.38)(P=0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.

Lingnan Fire-needle on Inhibiting Melanocyte Apoptosis in Vitiligo Model Mice by Regulating Hippo-YAP Signaling Pathway / 中山大学学报(医学科学版)

ObjectiveTo observe the effects of fire-needle of Lingnan on the vitiligo model after hydroquinone-induced oxidative stress based on the Hippo-YAP signaling pathway. MethodsC57BL/6 mice were randomly divided into normal group （Control）， model group （HQ）， HQ+fire-needle group （FA）， and positive control group （Halometasone）， with 8 mice in each group. The vitiligo model was prepared by hydroquinone （HQ）. The skin pathological changes were observed by depigmentation score， HE staining and Masson-Fontana. Elisa was used to detect the levels of tyrosinase （TYR）， malondialdehyde （MDA） and monoamine oxidase （MAO）.Western-blot and PCR were used to detect the expression of Yap1 and Tp73 among the groups. ResultsCompared with the control group， the epidermis and dermis were significantly thicker. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules were significantly decreased， and the depigmentation score was significantly reduced（P＜0.01）. The level of TYR decreased， and the levels of MDA and MAO increased after modeling（P＜0.01）. The expression of Yap1 and Tp73 were significantly reduced （P<0.01）. The dermis became thinner in the halometasone and FA group after treatment of 4 weeks. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules increased （P<0.05）. Compared with that of the HQ group， the level of TYR in the halometasone group and FA group was significantly increased （P<0.01）. The levels of MDA and MAO in the FA group were decreased （P<0.05）. The expressions of Yap1 and Tp73 in the FA group were significantly increased （P<0.01）， and their effects were better than those in the Halometasone group （P<0.05）. ConclusionsFire-needle of Lingnan protects melanocytes from oxidative stress by activating the Hippo-YAP pathway. It enhances the synthesis and function of melanocytes and promotes repigmentation by reducing the content and activity of oxidative stress products.

Visual quality observation of transepithelial photorefractive keratectomy and femtosecond small incision lenticule extraction for the correction of low myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the changes in corneal aberrations and the characteristics of visual quality after transepithelial photorefractive keratectomy(T-PRK)and femtosecond small incision lenticule extraction(SMILE)in the correction of low myopia.METHODS: Prospective cohort study. A total of 32 cases(32 eyes)with low myopia who underwent T-PRK surgery and 45 cases(45 eyes)of SMILE surgery at Weifang Eye Hospital from April 2021 to April 2022 were selected. The uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical equivalent(SE), corneal higher-order aberrations(HOAs)and objective visual quality were compared between the two groups.RESULTS:All patients completed the surgery successfully without complications such as infection. At 3mo postoperatively, the safety index was 1.13±0.16 and 1.16±0.17(P=0.48)and the efficacy index was 1.10±0.20 and 1.15±0.18(P=0.27)in the T-PRK and SMILE groups, respectively. The percentage of UCVA(LogMAR)≤0 in the T-PRK and SMILE groups was 94% and 98%, respectively. The percentage of the residual SE within ±0.5D was 88% and 87% in the two groups, respectively. The HOAs and spherical aberration in both groups were significantly increased(P≤0.01), and the increase was not statistically significant between the two groups(P=0.31, 0.89). There was no significant change in horizontal coma, horizontal trefoil and vertical trefoil in both groups(P&#x0026;#x003E;0.05). The vertical coma in SMILE group was significantly increased(P&#x0026;#x003C;0.001), while there was no significant change in T-PRK group(P&#x0026;#x003E;0.05), and the increase was significantly greater in SMILE group than in T-PRK group(P&#x0026;#x003C;0.001). There was no significant difference in objective scattering index(OSI), modulation transfer function cut off frequency(MTFcut off), Strehl ratio(SR), visual acuity(VA)100%, VA20% and VA9% between the two groups(P&#x0026;#x003E;0.05).CONCLUSION:Both T-PRK and SMILE showed good safety, efficacy, and visual quality in correcting low myopia, while SMILE induced more vertical coma than T-PRK.

Short-term visual quality observation of femtosecond laser small incision lenticule extraction and evolution implantable collamer lens implantation in the correction of moderate myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the short-term visual quality outcomes after femtosecond laser small incision lenticule extraction(SMILE)and evolution implantable collamer lens(EVO-ICL)implantation for the correction of moderate myopia.METHODS: Prospective control study. A total of 51 cases(51 eyes)with moderate myopia who underwent SMILE or EVO-ICL implantation surgery at Weifang Eye Hospital from April 2021 to February 2022 were selected. They were divided into SMILE group(30 patients, 30 eyes)and EVO-ICL group(21 patients, 21 eyes)according to the surgical methods. The changes of visual acuity [uncorrected distance visual acuity(UDVA), corrected distance visual acuity(CDVA)], diopter [spherical equivalent(SE)] and related parameters of optical quality analysis system(OQAS Ⅱ)were observed before surgery and at 1wk, 1 and 3mo after surgery, and the quality of vision(QoV)questionnaire was completed.RESULTS: At 3mo after surgery, the safety index(postoperative CDVA/preoperative CDVA)of SMILE gruop and EVO-ICL group were 1.20(1.00, 1.20)and 1.20(1.00, 1.38), respectively, the efficacy index(postoperative UDVA/preoperative CDVA)were 1.00(1.00, 1.20)and 1.00(1.00, 1.20), respectively, and the percentage of SE within ±0.50D was 87% and 100%, respectively. In SMILE group, the objective scattering index(OSI)was increased after surgery, while modulation transfer function cutoff frequency(MTF cutoff), contrast visual acuity(VA)100%, and VA20% at 1wk and 1mo after surgery, and Strehl ratio(SR)and VA9% at each time point after surgery were all decreased compared with those before surgery(all P&#x0026;#x003C;0.05). The OSI, MTF cutoff, SR and VA of EVO-ICL group showed no difference at each time point after surgery compared with those before surgery(all P&#x0026;#x003E;0.05). The most common visual symptoms after SMILE and EVO-ICL implantation were visual haze and halos, respectively.CONCLUSION: Both SMILE and EVO-ICL implantation have good safety, efficacy and predictability in the short term after the correction of moderate myopia. Both groups had visual symptoms after surgery, but the overall satisfaction of patients was high. Furthermore, EVO-ICL implantation has better objective visual quality performance.

Mechanism of blue light-induced ferroptosis in retinal pigment epithelium cells / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the occurrence and possible mechanism of blue light-induced ferroptosis in retinal pigment epithelial cells.METHODS: ARPE-19 cells cultured in vitro were irradiated by 405 nm blue light at 50 mW/cm2 irradiance with different duration and were divided into control, 16.3J/cm2, 32.6J/cm2, and 65.2J/cm2 groups; the 65.2J/cm2 group was defined as the high-level blue light irradiation group and cells were further divided into control, high-level blue light irradiation group and high-level blue light irradiation + ferroptosis inhibitor group. CCK-8 assay was used to detect cell viability, commercial kits were used to detect intracellular glutathione(GSH), ferrous iron and malondialdehyde(MDA)concentration, and Western blot was used to detect the relative expression of glutathione peroxidase 4(GPX4)and xCT proteins in cells.RESULTS: The decrease of ARPE-19 cell viability caused by blue light irradiation was dose-dependent, and the reduction of intracellular GSH concentration, the increase of ferrous iron concentration and MDA concentration were all caused by high-level blue light irradiation(all P&#x0026;#x003C;0.05); the ferroptosis inhibitor partially restored cell viability and recovered intracellular GSH, reduced concentrations of MDA and ferrous iron in the blue light irradiation group(all P&#x0026;#x003C;0.05). The relative expressions of GPX4 and xCT proteins were significantly decreased in the blue light irradiation group, and such change was alleviated by the ferroptosis inhibitor(P&#x0026;#x003C;0.05).CONCLUSION: Blue light irradiation may induce ferroptosis in RPE cells by targeting the xCT and GPX4-associated antioxidant pathways.

Structurally novel HDAC inhibitors based on the trans-β-arylacryl tetrahydroisoquinoline scaffold: the design, synthesis, and anti-cancer activity / 药学学报

In this study, a series of 18 histone deacetylases inhibitors (HDACis), derived from our in-house anti-cancer trans-β-arylacryl 1,2,3,4-tetrahydroisoquinoline-based scaffold, were designed, synthesized, and antitumor evaluated. HDAC1 inhibitory activity assay showed that compounds 13d-13f and 13m-13o demonstrated attractive enzymatic activity with IC50 at single-digit nanomolar or subnanomolar level.In addition, 13o exerted superior anti-proliferative activity (A549, IC50 = 0.89 μmol·L-1; HCT116, IC50 = 0.49 μmol·L-1) to that of vorinostat (SAHA).Besides,13e, with the most potent HDAC1 enzymatic activity (IC50 = 3.8 nmol·L-1), also displayed attractive cellular activity (A549, IC50 = 1.74 μmol·L-1; HCT116, IC50 = 2.43 μmol·L-1). The Western blot analysis illustrated that 13e treatment increased the acetylation of H3 and α-tubulin in a dose-dependent manner in A549 cells. In summary, 13e and 13o deserve further functional investigation.

Research progress of sphingosine kinase and sphingosine-1-phosphate (S1P) /S1P receptor signaling in tumor microenvironment / 药学学报

Sphingosine kinase (SphK), sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) are involved in the tumor biological processes such as tumor cell proliferation and migration, and play an important role in the development of cancer. In recent years, researchers have increasingly focused on the interaction between cancer cells and the tumor microenvironment. The tumor microenvironment is genetically stable and can be induced to an antitumor phenotype, which has significant therapeutic advantages. Studies have shown that SphK/S1P/S1PR can regulate multiple aspects of the tumor microenvironment. This review summarizes the effects of SphK and S1P/S1PR signaling on the tumor microenvironment from four perspectives: tumor immune microenvironment, cancer associated fibroblasts, tumor angiogenesis and tumor hypoxic microenvironment, and also outlines potential drug research related to these signal molecules, aiming to elucidate the role of SphK/S1P/S1PR in tumor occurrence and development and provide new ideas for the research of anti-tumor drugs.

Feasibility of outer membrane protein C as a protein presenting platform targeting antigen to surface of outer membrane vesicle / 中国生物制品学杂志

@#Abstract：Objective To investigate the feasibility of outer membrane protein C（OmpC）as a protein presenting platform targeting antigen to the surface of outer membrane vesicle（OMV）. Methods The recombinant expression plasmid containing ompC gene fragment and Staphylococcus aureus EsxA antigen gene（esxA gene）was constructed，transformed to competent E. coli BL21（DE3），inducedbyIPTG，andanalyzedforexpressedproductby 12%SDS⁃PAGE. Thetotalproteinofrecombinant strain OMV was analyzed by 12% SDS⁃PAGE，and the localization of fusion protein on the surface of OMV was detected by Western blot and Flow NanoAnalyzer. Results The recombinant expression plasmid containing ompC gene and esxA gene was constructed correctly as proved by sequencing. 12% SDS⁃PAGE showed that the fusion protein OmpC⁃EsxA had a relative molecular mass of about 57 000，which was consistent with the expected size，while the total protein of OMV showed multiple target protein bands，indicating that recombinant strain OMV was successfully extracted. The fusion protein OmpC⁃ EsxA on the surface of recombinant strain OMV specifically bound to mouse antibody against His⁃Tag，and OMVs labeled with fluorescent antibody were detected by Flow NanoAnalyzer. Conclusion OmpC may be used as a protein presenting plat⁃ form to locate antigen to OMV surface，which was expected to be applied in the development of antigen presentation vaccine. Keywords：Outer membrane protein C（OmpC）；Protein presentation；Outer membrane vesicle（OMV）

Mechanism of Marsdenia tenacissima against ovarian cancer based on network pharmacology and experimental verification / 中国中药杂志

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12β-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.

Interpretation on Consensus on drug-induced liver injury by CIOMS Working Group:liver injury attributed to herbal and dietary supplements / 中国中药杂志

With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.

Relationship between atherogenic index of plasma and childhood asthma / 中国当代儿科杂志

OBJECTIVES@#To explore the relationship between atherogenic index of plasma (AIP) and childhood asthma.@*METHODS@#This retrospective study included 86 children with asthma admitted to the Changzhou Second People's Hospital Affiliated to Nanjing Medical University from July 2020 to August 2022 as the asthma group and 149 healthy children undergoing physical examination during the same period as the control group. Metabolic parameters including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and blood glucose, as well as general information of the children such as height, weight, body mass index, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, and feeding history, were collected. Multivariable logistic regression analysis was used to study the relationship between AIP, triglycerides, and high-density lipoprotein cholesterol and asthma. The value of AIP, triglycerides, and high-density lipoprotein cholesterol for predicting asthma was assessed using receiver operating characteristic (ROC) curve analysis.@*RESULTS@#The AIP and triglyceride levels in the asthma group were significantly higher than those in the control group, while high-density lipoprotein cholesterol was significantly lower (P<0.05). However, there was no significant difference in total cholesterol and low-density lipoprotein cholesterol between the two groups (P>0.05). Before and after adjusting for height, weight, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, feeding method, and blood glucose, multivariable logistic regression analysis showed that AIP, triglycerides, and high-density lipoprotein cholesterol were associated with asthma (P<0.05). ROC curve analysis showed that the optimal cutoff value for predicting asthma with AIP was -0.333, with a sensitivity of 80.2%, specificity of 55.0%, positive predictive value of 50.71%, and negative predictive value of 82.85%. The area under the curve (AUC) for AIP in predicting asthma was significantly higher than that for triglycerides (P=0.009), but there was no significant difference in AUC between AIP and high-density lipoprotein cholesterol (P=0.686).@*CONCLUSIONS@#AIP, triglycerides, and high-density lipoprotein cholesterol are all associated with asthma. AIP has a higher value for predicting asthma than triglycerides and comparable value to high-density lipoprotein cholesterol.

Prognostic value and mechanism of long non-coding RNA DLEU1 in osteosarcoma / 中国骨伤

OBJECTIVE@#To investigate the prognostic value and mechanism of long non-coding RNA DLEU1(LncRNA DLEU1) in osteosarcoma.@*METHODS@#The tissue samples and clinical data of 86 patients with osteosarcoma treated by orthopaedic surgery in our hospital from January 2012 to December 2014 were retrospectively collected. The expression of LncRNA DLEU1 in pathological tissues was detected by qRT-PCR, then the patients were divided into high and low expression of LncRNA DLEU1 groups. Osteosarcoma cell line HOS was divided into two groups, down-regulated expression group (si-DLEU1 group) and negative control group (si-NC group). LncRNA DLEU1 siRNA and negative control sequence were transfected by Lipofectamine 3000. Chi-square test was used to analyze the relationship between the expression of LncRNA DLEU1 and the clinicopathological factors of osteosarcoma. Kaplan-Meier method was used to compare the difference of the overall survival rate of osteosarcoma patients between the high and low expression groups of LncRNA DLEU1. The risk factors affecting the overall survival rate of osteosarcoma were analyzed by single factor and multifactor analysis. The number of invasive cells in the two groups was determined and compared by Transwell assay.@*RESULTS@#The expression of LncRNA DLEU1 in osteosarcoma tissue was higher than that in adjacent tissues (P<0.001). The expression of LncRNA DLEU1 in human osteosarcoma cell lines (MG-63, U-2 OS, and HOS) was significantly higher than that in human osteoblast line hFOB 1.19 (P<0.001). The expression of LncRNA DLEU1 was significantly correlated with Enneking stage (P<0.001), distant metastasis (P=0.016), and histological grade (P=0.028). The 1-year overall survival rate of the LncRNA DLEU1 high expression group was significantly higher than that of the low expression group (90.7% vs 60.5%, P<0.001). The 5-year overall survival rate of the LncRNA DLEU1 high expression group was significantly higher than that of the low expression group (32.6% vs 11.6%, P<0.001). Univariate analysis showed that Enneking stage (P<0.001), tumor size (P=0.043), distant metastasis (P<0.001), histological grade (P<0.001), and expression of LncRNA DLEU1 (P<0.001) were risk factors for overall survival of osteosarcoma patients. Multivariate analysis showed that high expression of LncRNA DLEU1 [HR=1.948, 95% CI(1.141, 3.641), P=0.012] and distant metastasis[HR=4.108, 95% CI(2.169, 7.780), P<0.001] were independent risk factors for overall survival of osteosarcoma patients. The number of invasive cells in si-DLEU1 group was significantly lesser than that in si-NC group(139±13 vs 357±31, P<0.001).@*CONCLUSION@#High expression of LncRNA DLEU1 is a molecular marker affecting the prognosis of osteosarcoma patients. Downregulation of LncRNA DLEU1 can inhibit the invasion of osteosarcoma cells.

Effect of guarana on lipid metabolism in obese rats: a study based on lipidomics / 中国中药杂志

This study investigated the effect of guarana on plasma lipid metabolites in obese rats and analyzed its mechanism in the treatment of dyslipidemia in obesity. High-fat diet was used to establish obese rat models, and the therapeutic effect of guarana on obese rats was evaluated by measuring body weight, white fat, liver weight, and lipid content, as well as observing liver histomorphology. Lipid metabolites in plasma of rats in each group were detected by UHPLC-Q-TOF-MS lipidomics. The protein expressions of fatty acid synthase, acetyl-CoA carboxylase 1, triglyceride synthesis enzyme, carnitine palmitoyltransferase Ⅰ, and acetyl-coenzyme A acyltransferase 2 in rat liver were detected using Western blot. The results revealed that guarana significantly reduced body weight, white fat, and liver weight of obese rats due to high-fat diet, and alleviated dyslipidemia and liver steatosis. Lipidomics showed that some triglycerides and phospholipids were significantly elevated in the high-fat model group, and part of them was reduced after guarana treatment. Western blot found that guarana inhibited the expression of hepatic fatty acid and triglyceride synthesis-related proteins and increased the expression of fatty acid β-oxidation-related proteins. Abnormalities in triglyceride and phospholipid metabolism are the main characteristics of plasma lipid metabolism in obese rats induced by high-fat diet. Guarana may regulate partial triglyceride and phospholipid metabolism by inhibiting hepatic fatty acid and triglyceride synthesis and increasing fatty acid β-oxidation, thereby improving rat obesity and dyslipidemia.