Development and validation of a new risk assessment model for immunomodulatory drug-associated venous thrombosis among Chinese patients with multiple myeloma.

BACKGROUND: Individuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients. METHODS: We retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis. RESULTS: The overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively. CONCLUSIONS: The new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.

Secondary perichondrium patch to enhance cartilage graft during endoscopic cartilage myringoplasty.

OBJECTIVES: The aim of this study was to explore the method of adding a secondary perichondrium patch to enhance the primary cartilage-perichondrium patch during endoscopic myringoplasty and to evaluate the effectiveness of this method in terms of healing rate and post-operative hearing of patients with poor prognostic factors (eustachian tube dysfunction, large perforations, subtotal perforations, and anterior marginal perforations). DESIGN: This retrospective study analyzed a total of 80 patients (36 females and 44 males, median age of 40.55 years) who had received a secondary perichondrium patch during endoscopic cartilage myringoplasty. Patients were followed up for 6 months. Healing rates, complications, preoperative and postoperative pure-tone average (PTA) and air-bone gap (ABG) were analyzed. RESULTS: At 6-month follow-up, the healing rate of tympanic membrane was 97.5% (78/80). The mean pure-tone average (PTA) improved from 43.18 ± 14.57 dB HL pre-operatively to 27.08 ± 9.36 dB HL 6 months after the operation (P = 0.002). Similarly, the mean ABG improved from 19.05 ± 5.72 dB HL pre-operatively to 9.36 ± 3.75 dB HL (P = 0.0019) at 6 months after the operation. Major complications were not observed during follow-up. CONCLUSIONS: The use of a secondary perichondrium patch during endoscopic cartilage myringoplasty for large, subtotal and marginal tympanic membrane perforations achieved a high healing rate and a statistically significant hearing gain with low incidence of complications.

Effect of polyethylene glycol 400 on the pharmacokinetics and tissue distribution of baicalin by intravenous injection based on the enzyme activity of UGT1A8/1A9.

Baicalin (BG) is a bioactive flavonoid extracted from the dried root of the medicinal plant, Scutellaria radix (SR) (dicotyledonous family, Labiatae), and has several biological activities. Polyethylene glycol 400 (PEG400) has been used as a suitable solvent for several traditional Chinese medicines (TCM) and is often used as an excipient for the compound preparation of SR. However, the drug-excipient interactions between BG and PEG400 are still unknown. Herein, we evaluated the effect of a single intravenous PEG400 administration on the BG levels of rats using pharmacokinetic and tissue distribution studies. A liver microsome and recombinant enzyme incubation system were used to further confirm the interaction mechanism between PEG400 and UDP-glucuronosyltransferases (UGTs) (UGT1A8 and UGT1A9). The pharmacokinetic study demonstrated that following the co-intravenous administration of PEG400 and BG, the total clearance (CLz) of BG in the rat plasma decreased by 101.60% (p < 0.05), whereas the area under the plasma concentration-time curve (AUC)0-t and AUC0-inf increased by 144.59% (p < 0.05) and 140.05% (p < 0.05), respectively. Additionally, the tissue distribution study showed that the concentration of BG and baicalein-6-O-ß-D-glucuronide (B6G) in the tissues increased, whereas baicalein (B) in the tissues decreased, and the total amount of BG and its metabolites in tissues altered following the intravenous administration of PEG400. We further found that PEG400 induced the UGT1A8 and UGT1A9 enzyme activities by affecting the maximum enzymatic velocity (Vmax) and Michaelis-Menten constant (Km) values of UGT1A8 and UGT1A9. In conclusion, our results demonstrated that PEG400 interaction with UGTs altered the pharmacokinetic behaviors and tissue distribution characteristics of BG and its metabolites in rats.

Comparison of endoscopic and microscopic tympanoplasty in patients with chronic otitis media.

BACKGROUND: To compare the results between type I tympanoplasty performed with transcanal endoscopic ear surgery (TEES) and microscopic ear surgery (MES) for treatment of chronic otitis media in a homogenous group of patients. METHODS: A retrospective study was performed in our department between January 2011 and January 2016 to review primary type I tympanoplasty cases with a subtotal perforation, an intact ossicular chain, a dry ear for at least 1 month, normal middle ear mucosa, and a follow-up period of at least 6 months post surgery. The adoption of TEES or MES was divided temporally (before and since 2013). TEES was undertaken in 224 patients (224 ears) and MES in 121 patients (121 ears). RESULTS: The successful graft take rate was 94.64% (212/224) in the TEES group and 90.91% (110/121) in the MES group (P = 0.239). The improvements in the air conduction levels between the 2 groups were not statistically different at 1, 3, or 6 (> 6) months (P > 0.05) after surgery. The improvements in the air-bone gaps were not significantly different between the 2 groups (P > 0.05). The average hearing gains in the TEES group 6 (and > 6) months post surgery were 11.85 ± 5.47 dB, which was better than 10.48 ± 5.18 dB in the MES group (P = 0.031). The use of medical resources was lower in the TEES group than in the MES group regarding the average operating time (49.22 ± 8.24 min vs 81.22 ± 14.73 min, respectively; P < 0.0001). Patients receiving MES had a significant higher incidence of the wound problems (ear pain, numbness around the ears, and wet ear; P < 0.05). CONCLUSION: TEES for type I tympanoplasty seems to achieve a shorter operative time and ideal tympanic membrane healing rate and hearing results in patients with chronic otitis media.

[Observation on the efficacy of Eustachian tube dilation hormone under the guidance of endoscope in the treatment of sudden deafness].

Objective:To evaluate the efficacy of Eustachian tube dilation hormone under the guidance of otoscope in the treatment of patients with sudden deafness. Methods:One hundred and seventy-six patients（185 ears） with sudden deafness treated by otorhinolaryngology head and neck surgery in Shaanxi Provincial People's Hospital from January 2020 to December 2020 were selected. According to the inclusion and exclusion criteria, 176 patients（185 ears） were randomly divided into control group（n=86, 90 ears） and study group（n=90, 95 ears）. The control group was treated with intratympanic injection of methylprednisolone（methylprednisolone sodium succinate for injection）, and the study group was treated with tympanic tympanoplasty under otoendoscope. The pure tone hearing threshold, effective rate and the incidence of adverse reactions were compared between the two groups before and after treatment. Results:The total effective rate of the study group was 84.21%（80/95）, slightly lower than that of the control group（84.44%）, but there was no significant difference between the two groups. The hearing threshold of pure tone in the two groups was significantly higher than that before treatment, and the average improvement of hearing in the study group（25.47±6.29） dB was slightly lower than that in the control group（27.33±7.55） dB, but there was no significant difference between the two groups（P>0.05）. There was no significant difference in the incidence of mild adverse reactions between the two groups（P>0.05）. There were no serious adverse reactions. Conclusion:The total effective rate, hearing improvement level and adverse reaction rate of patients with sudden deafness treated with Eustachian tube tympanic dilatation hormone under endoscope are the same as that of tympanic hormone injection.

Novel P-n Li2SnO3/g-C3N4 Heterojunction With Enhanced Visible Light Photocatalytic Efficiency Toward Rhodamine B Degradation.

The design of highly efficient and stable photocatalysts to utilize solar energy is a significant challenge in photocatalysis. In this work, a series of novel p-n heterojunction photocatalysts, Li2SnO3/g-C3N4, was successfully prepared via a facile calcining method, and exhibited superior photocatalytic activity toward the photodegradation of Rhodamine B solution under visible light irradiation as compared with pure Li2SnO3 and g-C3N4. The maximum kinetic rate constant of photocatalytic degradation of Rhodamine B within 60 min was 0.0302 min-1, and the composites still retained excellent performance after four successive recycles. Chemical reactive species trapping experiments and electron paramagnetic resonance demonstrated that hydroxyl radicals (·OH) and superoxide ions ( · O 2 - ) were the dominant active species in the photocatalytic oxidation of Rhodamine B solution, while holes (h+) only played a minor role. We demonstrated that the enhancement of the photocatalytic activity could be assigned to the formation of a p-n junction photocatalytic system, which benefitted the efficient separation of photogenerated carriers. This study provides a visible light-responsive heterojunction photocatalyst with potential applications in environmental remediation.

In Situ Construction of a MgSn(OH)6 Perovskite/SnO2 Type-II Heterojunction: A Highly Efficient Photocatalyst towards Photodegradation of Tetracycline.

Using solar energy to remove antibiotics from aqueous environments via photocatalysis is highly desirable. In this work, a novel type-II heterojunction photocatalyst, MgSn(OH)6/SnO2, was successfully prepared via a facile one-pot in situ hydrothermal method at 220 °C for 24 h. The obtained heterojunctions were characterized via powder X-ray diffraction, Fourier-transform infrared spectroscopy, transmission electron microscopy, and ultraviolet-visible diffuse reflectance spectroscopy. The photocatalytic performance was evaluated for photodegradation of tetracycline solution under ultraviolet irradiation. The initial concentration of tetracycline solution was set to be 20 mg/L. The prepared heterojunctions exhibited superior photocatalytic activity compared with the parent MgSn(OH)6 and SnO2 compounds. Among them, the obtained MgSn(OH)6/SnO2 heterojunction with MgCl2·6H2O:SnCl4·5H2O = 4:5.2 (mmol) displayed the highest photocatalytic performance and the photodegradation efficiency conversion of 91% could be reached after 60 min under ultraviolet irradiation. The prepared heterojunction maintained its performance after four successive cycles of use. Active species trapping experiments demonstrated that holes were the dominant active species. Hydroxyl radicals and superoxide ions had minor effects on the photocatalytic oxidation of tetracycline. Photoelectrochemical measurements were used to investigate the photocatalytic mechanism. The enhancement of photocatalytic activity could be assigned to the formation of a type-II junction photocatalytic system, which was beneficial for efficient transfer and separation of photogenerated electrons and holes. This research provides an in situ growth strategy for the design of highly efficient photocatalysts for environmental restoration.

[The expression and clinical significance of pepsin and pepsinogen in patients with otitis media with effusion].

OBJECTIVE: To analyze the role and significance of pepsin and pepsinogen in the pathogenesis of OME in children. METHOD: Pediatric patients with otitis media aged 2-8 years who enrolled in our department of the hospital from May of 2012 to December of 2012 were set as experimental group (38 cases, 48 ears) which should be underwent tympanic membrane puncture/tube insertion. Meanwhile, pediatric patients waiting for cochlear implant without otitis media (10 ears), were set as control group. Middle ear lavage fluid and plasma samples from the two groups were collected and detected using enzyme-linked immune method for pepsin and pepsinogen. RESULT: The concentrations of pepsin and pepsinogen in the middle ear lavage fluid of OME group [(48.8 ± 415.99) ng/ml and 676.32 ± 336.71)ng/ml] were significantly higher than those in the control group [(8.20 ± 4.59)ng/ml and (77.27 ± 50.33) ng/ml] (P < 0.01). Meanwhile, the concentration of pepsinogen in the middle ear lavage of OME patients was significantly higher than that of plasma (P < 0.01). The concentration of pepsin in the middle ear lavage fluid from the dry ear subgroup was lower than those in the serum ear and mucous ear subgroups (P < 0.01), but there was no significant difference about concentrations of pepsinogen among the dry ear, serum ear and mucous ear subgroups (P > 0.05). CONCLUSION: Pepsin and pepsinogen in the middle ear cavity of OME patients maybe originated from laryngopharyngeal reflux (LPR), indicating that LPR is associated with the pathogenesis of OME in children.

Role of pepsin and pepsinogen: linking laryngopharyngeal reflux with otitis media with effusion in children.

OBJECTIVES/HYPOTHESIS: To analyze the relationship between laryngopharyngeal reflux (LPR) represented by pepsin and pepsinogen, and pathogenesis of otitis media with effusion (OME). STUDY DESIGN: Prospective case-control study. METHODS: Children with OME who required adenoidectomy and tympanostomy/tympanostomy tubes placement were enrolled in OME group, whereas children with adenoid hypertrophy (AH) who required adenoidectomy and individuals who required cochlear implantation (CI) were enrolled in AH and CI groups, respectively. Pepsinogen mRNA and protein levels were assessed by real-time fluorescence-based quantitative polymerase chain reaction and immunohistochemistry in adenoid specimens from the OME and AH groups. Pepsin and pepsinogen concentrations were evaluated by enzyme-linked immunosorbent assay in middle ear fluid and plasma from the OME and CI groups. RESULTS: The levels of pepsinogen protein expressed in cytoplasm of epithelial cells and clearance under epithelial cells in adenoid specimens from the OME group were significantly higher than those in the AH group. Furthermore, the concentrations of pepsin and pepsinogen in the OME group were 51.93±11.58 ng/mL and 728±342.6 ng/mL, respectively, which were significantly higher than those in the CI group (P<.001). In addition, the concentrations of pepsin in dry ears were significantly lower than those in serous and mucus ears in the OME group (F=22.77, P<.001).Finally, the concentration of pepsinogen in middle ear effusion was positively correlated with the expression intensity of pepsinogen protein in cytoplasm of epithelial cells (r=0.73, P<.05) in the OME group. CONCLUSIONS: Pepsin and pepsinogen in middle ear effusion are probably caused by LPR and may be involved in the pathogenesis of OME. LEVEL OF EVIDENCE: 3b.

[A meta analysis of gemcitabine plus platinum chemotherapy compared with single-agent chemotherapy in the treatment of non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: Whether gemcitabine plus platinum chemotherapy is superior to gemcitabine or platinum single-agent chemotherapy for patients with non-small cell lung cancer (NSCLC) is still in dispute, and the aim of this study is to evaluate the efficacy and safety of gemcitabine combining platinum chemotherapy for patients with NSCLC. METHODS: We searched relevant randomized controlled trials (RCTs) from VIP, CBM, CNKI, the Cochrane library, PUBMED and EMBASE. We traced the related references and experts in this field and communicated with other authors to obtain the information that has not been found. We made quality assessment of qualified RCTs assessed by the exclusion and inclusion criteria and used RevMan 5.0 provided by the Cochrane Collaboration to perform meta-analysis. RESULTS: Four RCTs were eligible and included 984 patients. Meta analysis results suggested that: compared with gecitabine single-agent chemotherapy, the combination had a statistically significant benefit in increasing the response rate (OR = 3.29, 95% CI: 1.79-6.05, P = 0.000 1) and 2-year survival rate (OR = 3.22, 95% CI: 1.45-7.12, P = 0.004) while increased the risk of the incidence of adverse reactions, especially the grade 3-4 thrombocytopenia (RR = 8.16, 95% CI: 1.71-39.07, P = 0.009); compared with cisplatin single-agent chemotherapy, the combination had a statistically significant benefit in increasing the response rate (OR = 3.51, 95% CI: 2.20-5.60, P < 0.01) and 1-year survival rate (OR = 1.67, 95% CI: 1.16-2.41, P = 0.006) while increased the risk of the incidence of adverse reactions, especially the grade 3-4 thrombocytopenia (OR = 28.55, 95% CI: 14.06-57.04, P < 0.01). CONCLUSION: Compared with single-agent chemotherapy, the combining can significantly improve the efficiency and survival rate while increase the toxicity rare. The results still need to be proved by high quality RCTs.

[A Systematic Review of Erlotinib for Advanced Non-small Cell Lung Cancer.].

BACKGROUND: It was unclear whether advanced non-small cell lung cancer (NSCLC) patients could benefit from erlotinib therapy. This study was aimed to evaluate the efficacy and safety of NSCLC patients treated with erlotinib. METHODS: The relevant randomized controlled trials (RCT) were searched from VIP, CMB, CNKI, PubMed, EMBASE and The Cochrane Library. The related references and experts in this field were traced, and other authors were communicated with to obtain the information that has not been found. Quality assessment of qualified RCTs assessed by the exclusion and inclusion criteria and RevMan 5.0 provided by the Cochrane Collaboration was used to perform meta-analysis. RESULTS: Three RCTs involving 2 969 patients were included. Meta analysis results suggested that erlotinib was superior to placebo for one year survival rate (OR=1.18, 95%CI: 1.01-1.38), tumor response rate (OR=1.24, 95%CI: 1.03-1.49), median overall survival, median progression-free survival and tumor responses duration. At the same time, the incidence of grade 3-4 skin rash (OR=16.33, 95%CI: 7.01-38.02) and diarrhea (OR=5.02, 95%CI: 2.93-8.60) of the adverse reactions was increased. CONCLUSIONS: Advanced non-small cell lung cancer patients could benefit from Erlotinib therapy, but the incidence of skin rash and diarrhea was significantly increased, and in the absence of damage to the blood system, serious liver and kidney damage, cardiac toxicity, etc, there were no difference with placebo.