1.Development of Chinese herbal medicine for sensorineural hearing loss.
Yunhao WU ; Jingwen ZHANG ; Qiuping LIU ; Zhuang MIAO ; Renjie CHAI ; Wenyong CHEN
Acta Pharmaceutica Sinica B 2024;14(2):455-467
According to the World Health Organization's world report on hearing, nearly 2.5 billion people worldwide will suffer from hearing loss by 2050, which may contribute to a severe impact on individual life quality and national economies. Sensorineural hearing loss (SNHL) occurs commonly as a result of noise exposure, aging, and ototoxic drugs, and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear, which is mainly triggered by reactive oxygen species accumulation, inflammation, and mitochondrial dysfunction. Though recent advances have been made in understanding the ability of cochlear repair and regeneration, there are still no effective therapeutic drugs for SNHL. Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine. Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL, and elucidate their molecular mechanisms of action, to pave the way for further research and development of novel effective drugs in this field.
2.Application of dual ultrafine 8F drainage tubes in single-port thoracoscopic lobectomy/segmentectomy: A retrospective cohort study
Weiya YAN ; Jiangnan WANG ; Jian CAI ; Xianhua WU ; Xuebing DING
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(12):1788-1793
Objective To examine the application effectiveness of dual 8F ultrafine pigtail drainage tubes versus a single 28F large-bore chest tube in single-port thoracoscopic lobectomy/segmentectomy. Methods Clinical data of patients who underwent single-port video-assisted thoracoscopic lobectomy/segmentectomy within our medical group from January 2020 to August 2023 were retrospectively analyzed. They were categorized into two groups based on postoperative drainage methods: a dual 8F ultrafine pigtail tubes group and a single 28F large-bore chest tube group. Comparative analysis was performed on perioperative data for the two groups of patients. Results The dual 8F ultrafine pigtail tubes group comprised of 68 patients, with 41 females and 27 males, and an average age of (54.72±13.34) years, while the single 28F large-bore chest tube group comprised of 80 patients, with 40 females and 40 males, and an average age of (57.60±11.04) years. There were statistical differences between the two groups in terms of postoperative drainage volume on day 1, day 2, and day 3, total postoperative drainage volume, postoperative tube placement time, postoperative pain score at 48 hours, maximum postoperative pain score, postoperative hospital stay, postoperative complications related to drainage tubes, and emergency use of pain-relieving medication after surgery (P<0.05). Conclusion After single-port thoracoscopic lobectomy/segmentectomy, the application of dual ultrafine 8F pigtail drainage tubes can lead to a reduction in postoperative drainage volume and shorten the duration of postoperative drainage tube placement and hospital stay, thereby decreasing postoperative pain and the frequency of emergency pain-relieving medication. Moreover, it lowers the incidence of drainage tube-related complications. In alignment with current enhanced recovery after surgery principles, this approach is advantageous for postoperative recovery.
3.Value of laser therapy, photodynamic therapy, and follow-up observation in the management of cervical low-grade squamous intraepithelial lesions: a prospective cohort study
Lu ZHANG ; Fanting MENG ; Jiangnan WU ; Long SUI ; Qing CONG
Chinese Journal of Obstetrics and Gynecology 2024;59(11):848-855
Objective:To explore the value of CO 2 laser therapy, photodynamic therapy, and follow-up observation in the management of cervical low-grade squamous intraepithelial lesion (LSIL). Methods:Women diagnosed with cervical LSIL and high risk human papillomavirus (HR-HPV) infection through colposcopy-guided biopsy from January 1, 2021 to December 31, 2023 were collected. According to a 1∶1 ratio, 107 cases were included in each of the laser treatment, photodynamic therapy, and follow-up groups. The complete remission rate and HR-HPV clearance rate were compared during the 6-12 months follow-up period.Results:(1) Comparison of clinical data among the three groups before treatment: the median age of the 321 patients was (34.9±8.1) years. Before treatment, cytological abnormalities were present in 51.7% (166/321) of patients, and 35.2% (113/321) had human papillomavirus (HPV) 16/18 infections. The accuracy rate of colposcopic diagnosis was 69.2% (222/321). Age, cytology results, HPV 16/18 infection, and colposcopy diagnosis in the laser group, photodynamic group, and follow-up group were compared, and there were not statistically significant differences (all P>0.05). (2) During the 6-12 months follow-up period, the complete remission rate was 89.7% (96/107) in the laser group, slightly higher than the 86.9% (93/107) in the photodynamic group, with no statistical difference between the two groups ( χ2=0.41, P=0.523). However, both were significantly higher than the 64.5% (69/107) in the follow-up group ( χ2=19.30, P<0.001; χ2=14.63, P<0.001). The HR-HPV clearance rates in the laser and photodynamic groups were 73.8% (79/107) and 68.2% (73/107), respectively, both significantly higher than the 32.7% (35/107) in the follow-up group ( χ2=36.34, P<0.001; χ2=26.99, P<0.001), but with no statistical difference between the laser and photodynamic groups ( χ2=0.82, P=0.366). Conclusions:CO 2 laser therapy and photodynamic therapy are effective treatments for cervical LSIL, significantly superior to follow-up observation in terms of lesion remission and HR-HPV clearance rates. Individualized treatment plans could be developed based on the patient′s age, duration of HR-HPV infection, colposcopic impression, and economic conditions.
4.Research progress of novel DNAzyme biosensing technology in liquid biopsy for tumors
Jiangnan ZENG ; Pan YANG ; Liyi LI ; Weiling FU ; Yongzhong WU ; Yang ZHANG
Chinese Journal of Laboratory Medicine 2024;47(11):1355-1360
Tumors pose a serious challenge to global public health. The sensitive and precise detection of tumor biomarkers is very important for early screening and diagnosis of cancers. DNAzymes with outstanding physical, chemical, and biological properties are widely applied in the design of biosensing strategies. By the use of sensing platforms such as fluorescence, electrochemistry, and surface-enhanced Raman scattering, DNAzymes facilitate the early screening and detection of tumors. This article summarizes the functional mechanism and common classifications of DNAzymes, and the updates of DNAzymes-based novel biosensing technologies within the field of liquid biopsy, expecting the technical challenges yet to be surmounted and future developmental directions.
5.Dermatophagoides farinae induces conjunctival epithelial cell damage to promote neutrophil migration and neutrophil extracellular traps formation
Meili WU ; Ru YAN ; Wenjun ZHAO
Chinese Journal of Schistosomiasis Control 2023;35(3):271-278
Objective To investigate the mechanisms underlying allergic conjunctivitis caused by conjunctival epithelial cell damage, neutrophil migration and neutrophil extracellular traps (NETs) formation induced by crude extracts of Dermatophagoides farinae mite (CDM). Methods Human conjunctival epithelial cells were stimulated with 500, 1 000, 2 000, 4 000 ng/mL, and the expression levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-8 were detected using quantitative real-time PCR (qPCR) assay and enzyme-linked immunosorbent assay (ELISA). The culture supernatant of human conjunctival epithelial cells was collected and co-cultured with neutrophils. Neutrophil migration was measured using Transwell migration assay, and the expression of NETs markers myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) was quantified using immunofluorescence staining. Neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA), and then NETs were collected for treatment of human conjunctival epithelial cells. Cell apoptosis was detected using flow cytometry, and the levels of IL-6, TNF-α, IFN-γ and IL-8 were measured in the cell culture supernatant using ELISA. Results Treatment with CDM at concentrations of 2 000 ng/mL and 4 000 ng/mL up-regulated IL-6, TNF-α, IFN-γ and IL-8 expression in human conjunctival epithelial cells. Following treatment with CDM at concentrations of 2 000 ng/mL and 4 000 ng/mL, the culture supernatant of human conjunctival epithelial cells promoted neutrophil migration and induced increases in the staining intensity of MPO and CitH3. In addition, increased NETs triggered the apoptosis of human conjunctival epithelial cells and IL-6, TNF-α, IFN-γ and IL-8 secretion in the culture supernatant of human conjunctival epithelial cells. Conclusions CDM induces human conjunctival epithelial cell damages, thereby promoting neutrophil migration and NETs formation, while the release of NETs further aggravates human conjunctival epithelial cell damages.
6.Application of cutinase in the degradation of biodegradable polyester poly(butylene adipate-co-terephthalate).
Hui WANG ; Jing WU ; Sheng CHEN ; Wei XIA
Chinese Journal of Biotechnology 2023;39(5):1987-1997
With the environmental pollution caused by waste plastics becoming increasingly serious, biodegradable polyester has become the focus of public attention. Poly(butylene adipate-co-terephthalate) (PBAT) is a biodegradable polyester formed by the copolymerization of aliphatic and aromatic groups, which has excellent performance of both. The degradation of PBAT under natural conditions requires strict environmental conditions and long degradation cycle. To address these shortcomings, this study explored the application of cutinase in PBAT degradation and the impact of butylene terephthalate (BT) content on the biodegradability of PBAT, so as to improve the degradation rate of PBAT. Five Polyester degrading enzymes from different sources were selected to degrade PBAT to pick out the most efficient enzyme. Subsequently, the degradation rate of PBAT materials with different BT content were determined and compared. The results showed that cutinase ICCG was the best enzyme for PBAT biodegradation, and the higher the BT content, the lower the degradation rate of PBAT. Furthermore, the optimum temperature, buffer type, pH, the ratio of enzyme to substrate (E/S) and substrate concentration in the degradation system were determined to be 75 ℃, Tris HCl, 9.0, 0.4% and 1.0% respectively. These findings may facilitate the application of cutinase in PBAT degradation.
Polyesters/chemistry*
;
Adipates
7.Modular engineering of Escherichia coli for high-level production of l-tryptophan.
Shuang DING ; Xiulai CHEN ; Cong GAO ; Wei SONG ; Jing WU ; Wanqing WEI ; Jia LIU ; Liming LIU
Chinese Journal of Biotechnology 2023;39(6):2359-2374
As an essential amino acid, l-tryptophan is widely used in food, feed and medicine sectors. Nowadays, microbial l-tryptophan production suffers from low productivity and yield. Here we construct a chassis E. coli TRP3 producing 11.80 g/L l-tryptophan, which was generated by knocking out the l-tryptophan operon repressor protein (trpR) and the l-tryptophan attenuator (trpL), and introducing the feedback-resistant mutant aroGfbr. On this basis, the l-tryptophan biosynthesis pathway was divided into three modules, including the central metabolic pathway module, the shikimic acid pathway to chorismate module and the chorismate to tryptophan module. Then we used promoter engineering approach to balance the three modules and obtained an engineered E. coli TRP9. After fed-batch cultures in a 5 L fermentor, tryptophan titer reached to 36.08 g/L, with a yield of 18.55%, which reached 81.7% of the maximum theoretical yield. The tryptophan producing strain with high yield laid a good foundation for large-scale production of tryptophan.
Escherichia coli/metabolism*
;
Tryptophan
;
Metabolic Engineering
;
Bioreactors
;
Metabolic Networks and Pathways
8.Metabolic engineering of Escherichia coli for adipic acid production.
Jie LIU ; Cong GAO ; Xiulai CHEN ; Liang GUO ; Wei SONG ; Jing WU ; Wanqing WEI ; Jia LIU ; Liming LIU
Chinese Journal of Biotechnology 2023;39(6):2375-2389
Adipic acid is a high-value-added dicarboxylic acid which is primarily used in the production of nylon-66 for manufacturing polyurethane foam and polyester resins. At present, the biosynthesis of adipic acid is hampered by its low production efficiency. By introducing the key enzymes of adipic acid reverse degradation pathway into a succinic acid overproducing strain Escherichia coli FMME N-2, an engineered E. coli JL00 capable of producing 0.34 g/L adipic acid was constructed. Subsequently, the expression level of the rate-limiting enzyme was optimized and the adipic acid titer in shake-flask fermentation increased to 0.87 g/L. Moreover, the supply of precursors was balanced by a combinatorial strategy consisting of deletion of sucD, over-expression of acs, and mutation of lpd, and the adipic acid titer of the resulting E. coli JL12 increased to 1.51 g/L. Finally, the fermentation process was optimized in a 5 L fermenter. After 72 h fed-batch fermentation, adipic acid titer reached 22.3 g/L with a yield of 0.25 g/g and a productivity of 0.31 g/(L·h). This work may serve as a technical reference for the biosynthesis of various dicarboxylic acids.
Escherichia coli/metabolism*
;
Metabolic Engineering
;
Bioreactors
;
Fermentation
;
Adipates/metabolism*
9.Light-driven CO2 conversion system: construction, optimization and application.
Yamei GAN ; Liang GUO ; Cong GAO ; Wei SONG ; Jing WU ; Liming LIU ; Xiulai CHEN
Chinese Journal of Biotechnology 2023;39(6):2390-2409
The use of light energy to drive carbon dioxide (CO2) reduction for production of chemicals is of great significance for relieving environmental pressure and solving energy crisis. Photocapture, photoelectricity conversion and CO2 fixation are the key factors affecting the efficiency of photosynthesis, and thus also affect the efficiency of CO2 utilization. To solve the above problems, this review systematically summarizes the construction, optimization and application of light-driven hybrid system from the perspective of combining biochemistry and metabolic engineering. We introduce the latest research progress of light-driven CO2 reduction for biosynthesis of chemicals from three aspects: enzyme hybrid system, biological hybrid system and application of these hybrid system. In the aspect of enzyme hybrid system, many strategies were adopted such as improving enzyme catalytic activity and enhancing enzyme stability. In the aspect of biological hybrid system, many methods were used including enhancing biological light harvesting capacity, optimizing reducing power supply and improving energy regeneration. In terms of the applications, hybrid systems have been used in the production of one-carbon compounds, biofuels and biofoods. Finally, the future development direction of artificial photosynthetic system is prospected from the aspects of nanomaterials (including organic and inorganic materials) and biocatalysts (including enzymes and microorganisms).
Carbon Dioxide/metabolism*
;
Photosynthesis
;
Metabolic Engineering
10.Analysis of natural regression and influencing factors of HSIL in the cervix of childbearing age patients.
Min Xia WU ; Xiao Ming HE ; Zhi Xue YOU
Chinese Journal of Obstetrics and Gynecology 2023;58(7):516-525
Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ2=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ2=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.
Pregnancy
;
Humans
;
Female
;
Adult
;
Cervix Uteri/pathology*
;
Uterine Cervical Neoplasms/pathology*
;
Uterine Cervical Dysplasia/pathology*
;
Biopsy
;
Colposcopy/methods*
;
Squamous Intraepithelial Lesions/pathology*
;
Carcinoma in Situ/pathology*
;
Papillomaviridae/genetics*
;
Papillomavirus Infections/diagnosis*
;
Squamous Intraepithelial Lesions of the Cervix/pathology*

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