Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.

A child aged 5 years with pulmonary arterial hypertension was admitted to the First Affiliated Hospital of Xiamen University in December 2017. A truncated mutation in the bone morphogenetic protein receptor 2 (BMPR2) gene [Chr2(GRCh37):g.203395656delA] was detected, which might be responsible for the disease and the diagnosis of hereditary pulmonary arterial hypertension (HPAH) was confirmed. Genetic testing revealed that the child′s father also carried the same mutation in BMPR2 gene, but no gene mutation was detected in child′s mother and young brother; however, no HPAH was developed in child′s father and other family members. The child was treated with targeted drugs for pulmonary arteries with poor response, and died in April 2019. Later, the child′s mother accidentally became pregnant. Gene sequencing test of the amniotic fluid showed that the fetus also carried the BMPR2 gene mutation; the pregnancy was terminated after genetic counseling. HPAH has the clinical characteristics of early onset, rapid progression, and poor prognosis, and the BMPR2 gene mutation is an important pathogenic factor. For HPAH patients with unknown etiology, particularly for pediatric patients, genetic testing is recommended to identify the cause and to make an appropriate clinical management plan.

A child aged 5 years with pulmonary arterial hypertension was admitted to the First Affiliated Hospital of Xiamen University in December 2017. A truncated mutation in the bone morphogenetic protein receptor 2 (BMPR2) gene [Chr2(GRCh37):g.203395656delA] was detected, which might be responsible for the disease and the diagnosis of hereditary pulmonary arterial hypertension (HPAH) was confirmed. Genetic testing revealed that the child′s father also carried the same mutation in BMPR2 gene, but no gene mutation was detected in child′s mother and young brother; however, no HPAH was developed in child′s father and other family members. The child was treated with targeted drugs for pulmonary arteries with poor response, and died in April 2019. Later, the child′s mother accidentally became pregnant. Gene sequencing test of the amniotic fluid showed that the fetus also carried the BMPR2 gene mutation; the pregnancy was terminated after genetic counseling. HPAH has the clinical characteristics of early onset, rapid progression, and poor prognosis, and the BMPR2 gene mutation is an important pathogenic factor. For HPAH patients with unknown etiology, particularly for pediatric patients, genetic testing is recommended to identify the cause and to make an appropriate clinical management plan.

Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG

Objective: To analyze the clinical application of the open supraclavicular approach in thyroidectomy. Methods: The clinical practicability of open supraclavicular thyroidectomy was explored by comparing the traditional anterior low arc incision thyroidectomy procedure with open supraclavicular thyroidectomy in terms of patients'aesthetic satisfaction, effectiveness of the operation, operation time, and so on. Result: Twenty-two cases of open supraclavicular thyroidectomy (group B) had better aesthetic satisfaction than 29 cases of traditional incision thyroidectomy (group A)(P<0.05), and had the same operative effect with traditional incision. Open supraclavicular thyroidectomy is associated with good aesthetic satisfaction, and has the same effect as the traditional incision does. Conclusions: Open supraclavicular thyroidectomy has good clinical value for benign thyroid tumors and some malignant tumors that require unilateral lobectomy, and even for tumors larger than the incision diameter. It has good aesthetic value while ensuring the curative effect of surgery.

OBJECTIVE:To conduct screening for the active ingredients of Ziziphus jujuba with neuroprotective effect and to il-luminate their mechanisms of action preliminarily. METHODS:After neuron-like cells (PC12 cells) were respectively cultured in the ingredient of Z. jujuba with polysaccharide enriched(1 mg/ml),that with polysaccharide removed(1 mg/ml),7 kinds of flavo-noid ingredients of Z. jujuba(catechin,procyanidine B2,epicatechin,hyperoside,rutin,quercetin-3-β-D-glucoside and kaempfer-ol-3-O-rutinoside,represented by A,B,C,D,E,F,G,all at the concentrations of 3,13,30 μmol/L)and 2 kinds of nucleoside ingredients of Z. jujuba (cyclic adenosine monophosphate and cyclic guanosine monophosphate,both at the concentrations of 3, 13,30 μmol/L)for 24 h,tert-butyl hydroperoxide(tBHP,150 μmol/L)was used to act on PC12 cells for 3 h to induce oxidative cellular damage,and MTT assay was employed to detect the survival rate of PC12 cells. The PC12 cells transfected with reporter gene plasmid(pARE-Luc)were cultured as above for 24 h,luciferase(Luc)assay was used to detect the transcriptional levels of the antioxidant response element(ARE)of all groups of cells(reflected as the activity of Luc)so as to investigate the anti-injury mechanism. RESULTS:The ingredient of Z. jujuba with polysaccharide enriched could significantly increase the survival rate of PC12 cells to which oxidative damage was caused and the transcriptional level of ARE in the transfected cells. Among the flavonoid ingredients of Z. jujuba, A(30 μmol/L),B(3-30 μmol/L)and C(10-30 μmol/L)could significantly increased the survival rate of the cells,and A(30 μmol/L),B(3-30 μmol/L),C(30 μmol/L),E(30 μmol/L)and F(3-30 μmol/L)could obviously in-creased the activation level of ARE in the transfected cells. However,the nucleoside ingredients of Z. jujuba including cyclic ade-nosine monophosphate and cyclic guanosine monophosphate had no obvious effect of increasing the survival rate of PC12 cells to which oxidative damage was caused or activating the transcription of ARE in the transfected cells. CONCLUSIONS:The polysac-charide and flavonoid ingredients of Z. jujuba may be the active ingredients which account for the neuroprotective effect against oxi-dative cellular damage,and their mechanisms of action may be related to the activation of ARE transcription.

During the production of ε-poly-L-lysine (ε-PL) in fed-batch fermentation, the decline of ε-PL synthesis often occurs at middle or late phase of the fermentation. To solve the problem, we adopted two strategies, namely pH shift and feeding yeast extract, to improve the productivity of ε-PL. ε-PL productivity in fermentation by pH shift and feeding yeast extract achieved 4.62 g/(L x d) and 5.16 g/(L x d), which were increased by 27.3% and 42.2% compared with the control ε-PL fed-batch fermentation, respectively. Meanwhile, ε-PL production enhanced 36.95 g/L and 41.32 g/L in 192 h with these two strategies, increased by 27.4% and 42.48% compared to the control, respectively. ε-PL production could be improved at middle or late phase of fed-batch fermentation by pH shift or feeding yeast extract.
Batch Cell Culture Techniques ; Fermentation ; Industrial Microbiology ; Nitrogen ; chemistry ; Polylysine ; biosynthesis

In this paper, chloramphenicol was selected as a model drug to prepare in situ gels. The intrinsic dissolution rate of chloramphenicol from in situ gel was evaluated using the surface dissolution imaging system. The results indicated that intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel decreased significantly when the poloxamer concentration increased. The addition of the thickener reduced the intrinsic dissolution rate of chloramphenicol thermosensitive gel, wherein carbomer had the most impact. Different dilution ratios of simulated tear fluid greatly affected gel temperature, and had little influence on the intrinsic dissolution rate of chloramphenicol from the thermosensitive in situ gel. The pH of simulated tear fluid had little influence on the intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel. For the pH sensitive in situ gel, the dissolution rates of chloramphenicol in weak acidic and neutral simulated tear fluids were slower than that in weak alkaline simulated tear fluid. In conclusion, the intrinsic dissolution of chloramphenicol from in situ gel was dependent on formulation and physiological factors. With advantages of small volume sample required and rapid detection, the UV imaging method can be an efficient tool for the evaluation of drug release characteristics of ophthalmic in situ gel.

Objective To observe the treatment effect of joint manipulation under brachial plexus anesthesia combined with comprehensive physical therapy in treatment of periarthritis of shoulder. Mehods From 2010.3 to 2010.9, 60 patients with periarthritis of shoulder in the Department of Pain, The First People's Hospital of Jingzhou,were divided into 3 groups:group A,B and C.Twenty patients in Group A were given Joint manipulation under brachial plexus anesthesia for treatment of the periarthritis of shoulder. Twenty patients in Group B were given comprehensive physical therapy fro treatment of periarthritis of shoulder. Twenty patients in Group C were given Joint manipulation under brachial plexus anesthesia combined with comprehensive physical therapy for treatment of periarthritis of shoulder.Results All 60 patients were followed up for 1 months. At the 1st month after surgery, vas score was evaluated for patients. Postoperative and preoperative vas score difference was compared between 3 groups by t test. There was statistically significant difference in the postoperative and preoperative vas score between Group C and Group A,and between Group B and Group A (P<0.05) . Conclusion The treatment effect of Joint manipulation under brachial plexus anesthesia combined with physical therapy in treatment of periarthritis of shoulder is good, but has no obvious difference compared with comprehensive physical therapy.

Objective To observe the treatment effect of radio frequency target combined with collagenase in treatment of cervical intervertebral disc herniation. Methods From March 2011 to September 2011, 40 patients with cervical intervertebral disc herniation were divided into 2 groups: Group A and Group B. Patients in Group A were given radio frequency target radiofrequency for treatment of the cervical intervertebral disc herniation and patients in Group B of 20 were given radio frequency target combined with collagenase for treatment of cervical intervertebral disc herniation. Results 40 patients were followed up for 6 months. At the 1st week and 6 months after surgery, the VAS score difference between before and after surgery in patients were compared between two groups by t test. There was no statistically significant difference at the 1st week after surgery between two groups (P>0.05), while 6 months after surgery, there was statistically significant difference between two groups (P<0.05) .Conclusion Radio frequency target combined with collagenase for treatment of cervical intervertebral disc herniation can alleviate the pain symptoms of patients,and the short-term and long-term curative effect is very good. The long-term curative effect has statistically significant difference with pure target radiofrequency ablation treatment. Radio frequency target combined with collagenase for treatment of cervical intervertebral disc herniation has good safety, few side effects, low risks and good short-term and long-term curative effect, so it deserves to be generalized.