1.Effects of polysorbates on stability of monoclonal antibody drugs
ZHU Sheng-ying ; CAO Jia-wei ; XU Jin ; CHEN Chen-hui ; GUO Qing-cheng ; LI Jun ; ZHANG Da-peng ; QIAN Wei-zhu ; HOU Sheng ; GUO Huai-zu
Chinese Journal of Biologicals 2023;36(2):172-177
Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.
2.Reprogramming Mycobacterium tuberculosis CRISPR System for Gene Editing and Genome-wide RNA Interference Screening
Rahman KHAISTA ; Jamal MUHAMMAD ; Chen XI ; Zhou WEI ; Yang BIN ; Zou YANYAN ; Xu WEIZE ; Lei YINGYING ; Wu CHENGCHAO ; Cao XIAOJIAN ; Tyagi ROHIT ; Naeem Ahsan MUHAMMAD ; Lin DA ; Habib ZESHAN ; Peng NAN ; F.Fu ZHEN ; Cao GANG
Genomics, Proteomics & Bioinformatics 2022;(6):1180-1196
Mycobacterium tuberculosis is the causative agent of tuberculosis(TB),which is still the leading cause of mortality from a single infectious disease worldwide.The development of novel anti-TB drugs and vaccines is severely hampered by the complicated and time-consuming genetic manipulation techniques for M.tuberculosis.Here,we harnessed an endogenous type Ⅲ-A CRISPR/Cas10 system of M.tuberculosis for efficient gene editing and RNA interference(RNAi).This simple and easy method only needs to transform a single mini-CRISPR array plasmid,thus avoiding the introduction of exogenous protein and minimizing proteotoxicity.We demonstrated that M.tuberculosis genes can be efficiently and specifically knocked in/out by this system as con-firmed by DNA high-throughput sequencing.This system was further applied to single-and multiple-gene RNAi.Moreover,we successfully performed genome-wide RNAi screening to identify M.tuberculosis genes regulating in vitro and intracellular growth.This system can be extensively used for exploring the functional genomics of M.tuberculosis and facilitate the development of novel anti-TB drugs and vaccines.
3.Clinical effects of free transplantation of expanded thoracodorsal artery perforator flaps in reconstructing cervical cicatrix contracture deformity after burns.
Peng JI ; Tao CAO ; Zhi ZHANG ; Yue ZHANG ; Shi Jun HU ; Jun Chang WANG ; Chao HAN ; Jing WANG ; Ji Hong SHI ; Da Hai HU ; Ke TAO
Chinese Journal of Burns 2022;38(4):328-334
Objective: To explore the clinical effects of free transplantation of expanded thoracodorsal artery perforator flaps in reconstructing cervical cicatrix contracture deformity after burns. Methods: A retrospective observational study was conducted. From May 2018 to April 2021, 11 patients with cervical cicatrix contracture deformity after burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 3 males and 8 females, aged 5 to 46 years, with a course of cervical cicatrix contracture deformity of 5 months to 8 years. The degree of cervical cicatrix contracture deformity was degree Ⅰ in one patient, degree Ⅱ in nine patients, and degree Ⅲ in one patient. In the first stage, according to the sizes of neck scars, one rectangular skin and soft tissue expander (hereinafter referred to as expander) with rated capacity of 200 to 600 mL was placed in the back. The expansion time was 4 to 12 months with the total normal saline injection volume being 3.0 to 3.5 times of the rated capacity of expander. In the second stage, free expanded thoracodorsal artery perforator flaps with areas of 10 cm×7 cm to 24 cm×13 cm were cut out to repair the wounds with areas of 9 cm×6 cm to 23 cm×12 cm which was formed after cervical cicatectomy. The main trunk of thoracodorsal artery and vein were selected for end-to-end anastomosis with facial artery and vein, and the donor sites were directly closed. The survival of flaps and healing of flap donor sites were observed on the 14th day post surgery. The appearances and cicatrix contracture deformity of the flaps, recovery of cervical function, and scar hyperplasia of donor sites were followed up. Results: On the 14th day post surgery, the flaps of ten patients survived, while ecchymosis and epidermal necrosis occurred in the center of flap of one patient and healed 2 weeks after dressing change. On the 14th day post surgery, the flap donor sites of 11 patients all healed well. During the follow-up of 6-12 months post surgery, the flaps of ten patients were similar to the skin around the recipient site in texture and color, while the flap of one patient was slightly swollen. All of the 11 patients had good recovery of cervical function and no obvious scar hyperplasia nor contracture in the flaps or at the donor sites. Conclusions: Application of expanded thoracodorsal artery perforator flaps can restore the appearance and function of the neck, and cause little damage to the donor site in reconstructing the cervical cicatrix contracture deformity after burns, which is worthy of clinical reference and application.
Arteries
;
Burns/surgery*
;
Cicatrix/surgery*
;
Contracture/surgery*
;
Female
;
Humans
;
Hyperplasia
;
Male
;
Perforator Flap
;
Reconstructive Surgical Procedures
;
Skin Transplantation
;
Soft Tissue Injuries/surgery*
;
Treatment Outcome
4.Effects of expanded frontal-parietal pedicled flap in reconstructing cervical scar contracture deformity in children after burns.
Cheng De XIA ; Ji Dong XUE ; Pei Peng XING ; Hai Na GUO ; Da Yong CAO ; Jiang Fan XIE ; Da Wei HAN ; Hai Ping DI
Chinese Journal of Burns 2022;38(5):454-461
Objective: To explore the effects of expanded frontal-parietal pedicled flap in reconstructing cervical scar contracture deformity in children after burns. Methods: A retrospective observational study was conducted. From January 2015 to December 2020, 18 male children with cervical scar contracture deformity after burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, aged 4 to 12 years, including 10 cases with degree Ⅱ cervical scar contracture deformity and 8 cases with degree Ⅲ scar contracture deformity, and were all reconstructed with expanded frontal-parietal pedicled flap. The surgery was performed in 3 stages. In the first stage, a cylindrical skin and soft tissue expander (hereinafter referred to as expander) with rated capacity of 300 to 500 mL was placed in the frontal-parietal region. The expansion time was 4 to 6 months with the total normal saline injection volume being 2.1 to 3.0 times of the rated capacity of expander. In the second stage, expander removal, scar excision, contracture release, and flap transfer were performed, with the flap areas of 18 cm×9 cm to 23 cm×13 cm and the secondary wound areas of 16 cm×8 cm to 21 cm×11 cm after scar excision and contracture release. After 3 to 4 weeks, in the third stage, the flap pedicle was cut off and restored. The rated volume of placed expander, total normal saline injection volume, type of vascular pedicle of flap, survival of flap and reconstruction of scar after the second stage surgery were recorded. The neck range of motion and cervico-mental angle were measured before surgery and one-year after surgery. The appearance of neck, occurrence of common complications in the donor and recipient sites of children, and satisfaction of children's families for treatment effects were followed up. Data were statistically analyzed with paired sample t test. Results: All the patients successfully completed the three stages of operation. The rated volume of implanted expander was 300 mL in 6 children, 400 mL in 9 children, and 500 mL in 3 children, with the volume of normal saline injection being 630 to 1 500 mL. The type of vascular pedicle of flap was double pedicle in 13 cases and was single pedicle in 5 cases. All the flaps in 17 children survived well, and the secondary wounds after neck scar excision and contracture release were all reconstructed in one procedure. In one case, the distal blood supply of the single pedicled flap was poor after the second stage surgery, with necrosis of about 2.5 cm in length. The distal necrotic tissue was removed on 10 days after the operation, and the wound was completely closed after the flap was repositioned. In the follow-up of 6 months to 3 years post operation, the cervical scar contracture deformity in 18 children was corrected without recurrence. The flap was not bloated, the texture was soft, and the appearances of chin and neck were good. The range of motion of cervical pre-buckling, extension, left flexion, and right flexion, and cervico-mental angle in one year after operation were improved compared with those before operation (with t values of 43.10, 22.64, 27.96, 20.59, and 88.42, respectively, P<0.01). The incision in the frontal donor site was located in the hairline, the scar was slight and concealed. No complication such as cranial depression was observed in expander placement site, and the children's families were satisfied with the result of reconstruction. Conclusions: Application of expanded frontal-parietal pedicled flap in reconstructing the cervical scar contracture deformity in children after burns can obviously improve the appearance and function of neck, with unlikely recurrence of postoperative scar contractures, thus it is an ideal method of reconstruction.
Burns/surgery*
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Child
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Cicatrix/surgery*
;
Contracture/surgery*
;
Humans
;
Male
;
Perforator Flap
;
Reconstructive Surgical Procedures/methods*
;
Saline Solution
;
Skin Transplantation
;
Treatment Outcome
5.Neoadjuvant chemotherapy for patients with locally advanced penile cancer: an updated evidence.
Xian-Yan-Ling YI ; De-Hong CAO ; Ping-Hong YOU ; Xing-Yu XIONG ; Xiao-Nan ZHENG ; Ge PENG ; Da-Zhou LIAO ; Hong LI ; Lu YANG ; Jian-Zhong AI
Asian Journal of Andrology 2022;24(2):180-185
Neoadjuvant chemotherapy (NAC) has shown promising results in patients with locally advanced penile cancer. However, no consensus exists on its applications for locally advanced penile cancer. Thus, it is unclear which kind of chemotherapy regimen is the best choice. Consequently, a systematic search of PubMed, Web of Science, and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer. The Newcastle-Ottawa Scale was used to assess the risk of bias in each study. This study synthesized 14 published studies. The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response. In addition, the objective response rates (ORRs) and pathological complete response (pCR) rates were 0.57 and 0.11, respectively. The incidence of grade ≥3 toxicity was 0.36. Subgroup analysis found that the ORR and pCR of the taxane-platinum (TP) regimen group performed better than those of the nontaxane-platinum (NTP) regimen group (0.57 vs 0.54 and 0.14 vs 0.07, respectively). Moreover, the TP regimen group had more frequent toxicity than the NTP regimen group (0.41 vs 0.26). However, further studies were warranted to confirm the findings.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Humans
;
Male
;
Neoadjuvant Therapy/methods*
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Penile Neoplasms/drug therapy*
;
Platinum
;
Treatment Outcome
6.Reconstruction of teaching mode of Human Parasitology among rural order-oriented medical students in the context of curriculum ideology and politics
De-ping CAO ; Li-ping JIANG ; Gen CHEN ; Da-yu LI ; Gang MO ; Xiao-hong PENG
Chinese Journal of Schistosomiasis Control 2022;34(2):187-190
To set the cultivation goal with adaptation to rural order-oriented medical students, the teaching mode of Human Parasitology was reformed in the context of curriculum ideological and political education. The new teaching mode not only enables students to harvest medical knowledge during the school education stage, but also plays a guiding role in cultivation of humanistic qualities and professional spirit, which provides a basis for cultivating general practitioners serving for grassroots healthcare.
8.Differences of Energy Spectrum CT Findings between Small Cell Lung Cancer with Mediastinal Lymph Node Metastasis and Mediastinal Sarcoidosis.
Tuo MA ; Li Xiu CAO ; Hui Ju LI ; Hong Liang REN ; Da Peng CHEN ; Yuan GAO ; Zhi Dong LI ; Xin Bin ZHAO ; Si Qi DONG
Acta Academiae Medicinae Sinicae 2021;43(1):53-56
Objective To compare the differences of energy spectrum CT between small cell lung cancer(SCLC)with mediastinal lymph node metastasis and mediastinal sarcoidosis.Methods Twenty-five SCLC patients with mediastinal lymph node metastasis(SCLC group)and 26 patients with mediastinal sarcoidosis(sarcoidosis group)confirmed by bronchoscopy and biopsy in Tangshan People's Hospital from January 2018 to June 2019 were selected as the research objects.The CT value,iodine concentration,water concentration and energy spectrum curve slope under different single energy levels were compared between SCLC group and sarcoidosis group.Results The single-energy CT values of 40-80 keV segments in the arterial phase of the SCLC group were significantly higher than those in the sarcoidosis group(all P <0.05).The single-energy CT values of 90-140 keV segments were not significantly different from those in the sarcoidosis group(all P >0.05).The single-energy CT values of 40-90 keV segments in venous phase of the SCLC group were significantly higher than those of the sarcoidosis group(all P <0.05),and the single-energy CT values of 100-140 keV segments were not significantly different from those of the sarcoidosis group(all P >0.05).The concentrations of iodine in the arterial phase and venous phase of the SCLC group were(11.56±4.06)μg/cm
Humans
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Lung Neoplasms/diagnostic imaging*
;
Lymph Nodes
;
Lymphatic Metastasis
;
Sarcoidosis/diagnostic imaging*
;
Small Cell Lung Carcinoma/diagnostic imaging*
;
Tomography, X-Ray Computed
9.Neurological Diseases Responding Specifically to Traditional Chinese Medicine
Ling-bo KONG ; Shu-yan WANG ; Xiao-ling LIAO ; Li ZHOU ; Ke-gang CAO ; Zhi-peng YU ; Huan-qin LI ; Geng LI ; Chao-yang HUANG ; Xi-yan XIN ; Zhi-chen ZHANG ; Wang-shu XU ; Da-yong MA ; Xiao-xiao ZHANG ; Ying GAO
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(13):172-178
In recent years, the incidence of neurological diseases has been increasing year by year. To give full play to the advantages of traditional Chinese medicine (TCM) in the treatment of neurological disorders, identify the breakthrough point of integrating TCM with western medicine, and further standardize the clinical diagnosis and treatment of TCM, the China Association of Chinese Medicine organized neurologists in TCM and western medicine to carry out in-depth discussion on the neurological diseases responding specifically to TCM and integrated TCM and western medicine, such as stroke, headache, vertigo, multiple sclerosis, and epilepsy, aiming to formulate a well-recognized and integrated treatment protocol for TCM and western medicine and improve the efficacy of neurological disorders. Furthermore, the treatment suggestions of the corresponding diseases in TCM and western medicine were proposed to provide references for clinical practice and scientific research.
10.Implication of enhanced recovery after surgery in the surgical management of hypopharyngeal squamous cell carcinoma.
Sheng Da CAO ; Wen Ming LI ; Dong Min WEI ; Ye QIAN ; Hua JIANG ; Yue Dong HOU ; Da Peng LEI ; Xin Liang PAN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2021;56(3):216-220
Objective: To investigate the safety and efficacy of enhanced recovery after surgery (ERAS) in the clinical management of hypopharyngeal squamous cell carcinoma (HSCC). Methods: In this retrospective study, a total of 168 patients with pyriform sinus carcinoma in Qilu Hospital of Shandong University from January 2015 to January 2019 were divided into two groups, based on the different perioperative interventions that patients received, i.e. the ERAS group (n=64) and the conventional group (n=104), including 164 males and 4 females, whose ages ranged from 42 to 84 years old. The difference between two groups in the operative time, postoperative nutritional status, incidences of postoperative complications and postoperative hospitalization time were compared using the student's t test, Chi-squared test or Fisher's exact test. Results: Compared with the conventional group, patients in the ERAS group had significantly shorter operative time [(166.8±58.2) min vs. (183.3±39.9) min,t=-2.72, P=0.031], higher levels of postoperative serum albumin [(38.3±4.2) μmol/L vs. (36.6±3.3) μmol/L, t=2.73, P=0.007] and more body weight [(65.4±9.4) kg vs. (62.1±9.4) kg, t=2.22, P=0.028], lower incidences of postoperative subcutaneous infection [7.8% (5/64) vs. 20.2% (21/104), χ²=4.64, P=0.03] and severe pneumonia [4.7% (3/64) vs. 15.4% (16/104), χ²=4.52, P=0.03], and shorter postoperative hospitalization time [(16.5±3.9) d vs. (18.2±4.3) d, t=-2.65, P<0.05]. Conclusion: ERAS is effective and safe in the surgical management of HSCC, with benefits in reducing the operative stress via saving operation time, shortening the hospitalization time, ameliorating nutritional status and decreasing the incidences of complications.
Adult
;
Aged
;
Aged, 80 and over
;
Enhanced Recovery After Surgery
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Female
;
Head and Neck Neoplasms
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Humans
;
Length of Stay
;
Male
;
Middle Aged
;
Postoperative Complications/epidemiology*
;
Retrospective Studies
;
Squamous Cell Carcinoma of Head and Neck
;
Treatment Outcome


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