OBJECTIVE To prepare Arg-Gly-Asp（RGD）-modified doxorubicin （DOX）-loaded “core-shell” nanoparticles （RGD@DOX-LPNs）， characterize the nanoparticles， and investigate their antitumor effects. METHODS RGD@DOX-LPNs were prepared using the nanoprecipitation method. Their morphology was examined by visual inspection and electron microscopy. Particle size， polydispersity index （PDI）， and Zeta potential were determined， and differential scanning calorimetry （DSC） and X-ray diffraction （XRD） were employed. Encapsulation efficiency （EE）， drug loading （DL）， and stability were evaluated. The in vitro release kinetics， mucus diffusion， and tumor cell uptake [tracked using coumarin 6 （COU）] were investigated. The in vivo tissue distribution and gastrointestinal retention [labeled with 11-chloro-1， 1′-dipropyl-3， 3， 3′， 3′-tetramethyl-10， 12- trimethyleneindotricarbocyanine iodide （IR780）] were investigated. Using 4T1 tumor-bearing mice as the experimental subjects， the effects of the prepared formulation on tumor volume， tumor weight， and cell apoptosis rate were evaluated. RESULTS RGD@DOX-LPNs presented as orange transparent liquid with uniform and near-spherical particles. The particle size was （159.67± 8.02） nm， PDI was 0.15±0.06， and Zeta potential was （－19.70±0.79） mV. After modification with RGD， the thermal absorption peak and crystalline diffraction peak of DOX disappeared. EE and DL of RGD@DOX-LPNs were （72.65±4.37）% and （4.62± 0.38）% ， respectively. No obvious changes in appearance， particle size， or EE were observed after storage at 4 ℃ and 25 ℃ for 7 days. The cumulative drug release at 4 h was approximately 73%， which was lower than that of free DOX（almost completely released within 1 h）. The amount of COU in the first segmental mucus layer of COU-LPNs was significantly lower than that in the corresponding segment of RGD@COU- LPNs， whereas it was significantly higher in the 2nd to 5th segmental mucus layers compared to RGD@COU-LPNs （P＜0.01）. Cellular uptake of RGD@COU-LPNs was significantly higher than that of COU-LPNs（P＜0.05）. The isolated tissue fluorescence intensity of RGD@IR780-LPNs was stronger than that of IR780-LPNs， indicating better small intestinal retention. Compared with free DOX and unmodified nanoparticles （DOX-LPNs）， RGD@DOX-LPNs exhibited a higher tumor inhibition rate of 65.74%， significantly reduced tumor volume and weight， and increased apoptosis rate（P＜0.01）. CONCLUSIONS RGD@DOX-LPNs are successfully prepared with sustained release properties， which can improve gastrointestinal mucus retention， enhance cellular uptake of DOX， and have potent antitumor activity against breast cancer.

Schizophrenia is a serious and highly disabling mental disorder, its pathogenesis is complex and unclear, and there is still a lack of objective clinical diagnosis and treatment indicators. A large amount of evidence had shown that genetic factors play important roles in the development and prognosis of schizophrenia, and genetic-related markers have great application prospects. This paper reviews the research on candidate genetic biomarkers of schizophrenia in order to provide reference for the precise diagnosis and treatment of schizophrenia.

Schizophrenia is a serious and highly disabling mental disorder, its pathogenesis is complex and unclear, and there is still a lack of objective clinical diagnosis and treatment indicators. A large amount of evidence had shown that genetic factors play important roles in the development and prognosis of schizophrenia, and genetic-related markers have great application prospects. This paper reviews the research on candidate genetic biomarkers of schizophrenia in order to provide reference for the precise diagnosis and treatment of schizophrenia.

Objective:To evaluate the clinical efficacy and safety of a skin care ointment containing oligomeric maltose X in the adjuvant treatment of eczema-related pruritus.Methods:A multicenter, randomized, double-blind, vehicle-controlled clinical study was conducted. From March to September 2021, outpatients with mild to moderate eczema were collected from departments of dermatology of 4 hospitals, including Beijing Friendship Hospital, Hebei Traditional Chinese Medical Hospital, the Third People′s Hospital of Hubei Province, and Taizhou Central Hospital in Zhejiang Province. The patients were randomly divided into two groups by using a random number table: observation group topically treated with a skin care ointment containing oligomeric maltose X, and vehicle control group topically treated with an ointment vehicle. The ointments were applied during the attacks of itching for 14 consecutive days. Visits were scheduled before, 7, and 14 days after the start of the adjuvant treatment. The efficacy was evaluated according to the eczema area and severity index (EASI) and visual analog scale (VAS) , and adverse events were recorded. The efficacy and safety analyses were conducted by using chi-square test and t test. Results:Totally, 232 patients with eczema were enrolled, including 90 males and 142 females, with the age being 40.13 ± 13.36 years; 156 patients were in the observation group, and 76 in the vehicle control group. Before the adjuvant treatment, there were no significant differences in EASI (2.07 ± 2.24 points vs. 2.29 ± 2.28 points) or VAS (6.22 ± 1.78 points vs. 6.20 ± 1.79 points) scores between the observation group and vehicle control group ( t = -0.70, 0.06, P = 0.486, 0.955, respectively) . After one-day treatment, the VAS scores significantly decreased compared with the baseline scores in the two groups ( P < 0.001, P = 0.003, respectively) . After 14-day treatment, the VAS score was significantly lower in the observation group (2.67 points) than in the vehicle control group (3.35 points; t = -2.28, P = 0.024) . After 7- and 14-day treatment, the EASI scores significantly decreased compared with the baseline scores in both the two groups (all P < 0.001) , but there were no significant differences between the two groups ( P = 0.853, 0.731) . No adjuvant treatment-related adverse events were recorded in either of the two groups. Conclusion:The skin care ointment containing oligomeric maltose X is safe and effective in the adjuvant treatment of eczema-related pruritus, and can be applied to clinical practice.

Oral and maxillofacial organoids (OMOs), tiny tissues and organs derived from stem cells cultured through 3-d cell culture models, can fully summarize the cell tissue structure, physiological functions and biological characteristics of the source tissues in the body. OMOs are applied in areas such as disease modelling, developmental and regenerative medicine, drug screening, personalized treatment, etc. Although the construction of organoids in various parts of the oral and maxillofacial (OM) region has achieved considerable success, the existing cocktail formulae (construction strategies) are not widely applicable for tissues of various sources due to factors including the heterogeneity of the source tissues and the dependence on laboratory technology. Most of their formulae are based on growth factor niches containing expensive recombinant proteins with their efficiency remaining to be improved. In view of this, the cocktail formulae of various parts of the OM organs are reviewed with further discussion of the application and prospects for those OMOs to find some affordable cocktail formula with strong operability and high repeatability for various maxillofacial organs. The results may help improve the efficiency of organoid construction in the laboratory and accelerate the pace of the clinical use of organoid technology.

Objective:To summarize the clinical manifestations of a case of combined oxidative phosphorylation deficiency 28 (COXPD-28) caused by the mutations of the SLC25A26 gene, thus providing references for the diagnosis and genetic counseling of the disease. Methods:Clinical data of a case of COXPD-28 treated in the Third Affiliated Hospital of Zhengzhou University in October 2020 were retrospectively analyzed.In addition, The retrieval words " Combined oxidative phosphorylation deficiency 28, SLC25A26 gene" were used to search domestic and foreign databases.The clinical characteristics of combined phosphorylation deficiency 28 and the variation characteristics of SLC25A26 gene were summarized. Results:(1) A female patient full-term delivered after 30 min presented with groaning breath was admitted.Her main manifestations included pale complexion, groaning breathing, metabolic acidosis, and high lactate and pyruvate levels.Symptomatic support treatment like anti-infection and assisted ventilation were given, but her condition gradually worsened and died of respiratory and circulatory failure on the day of admission.The child was compound heterozygous mutation of SLC25A26 gene, the terminating mutation of exon 5 c. 403G>T caused the protein change to p. E135, and the non-synonymous mutation of exon 4 c. 212A>G caused the protein change to p. Y71C.(2) A total of 3 cases of COXPD-28 were searched in online databases, and no cases were reported in China.Through literature review, clinical features of COXPD-28 mainly included respiratory and circulatory fai-lure, elevations of lactate and pyruvate, and reductions of complexes Ⅰ, Ⅲ and Ⅳ in muscle biopsy.Two types of mutations in the SLC25A26 gene were detected, including 3 cases of missense mutations and 1 case of splicing mutation. Conclusions:COXPD-28 is an autosomal recessive genetic disease involving multiple systems and mitochondrial dysfunction.Mutations in the SLC25A26 gene is the pathological cause of COXPD-28.

Klein-Levin syndrome is a chronic recurrent sleep disorder characterized by periodic excessive sleep, which can be accompanied by cognitive dysfunction, eating disorders, behavioral disorders, sensory disorders and emotional disorders, etc. During interval, individual′s daily functions are completely normal. Most of the KLS cases are sporadic. At present, only 17 familial cases of KLS have been reported abroad, while domestic reports in China are rare. We analyzed the detailed medical history, laboratory examinations, differential diagnosis, and the disease prevalence amongst family members of a patient with familial KLS, in order to provide reference for the follow-up study of familial cases of KLS.

Klein-Levin syndrome is a chronic recurrent sleep disorder characterized by periodic excessive sleep, which can be accompanied by cognitive dysfunction, eating disorders, behavioral disorders, sensory disorders and emotional disorders, etc. During interval, individual′s daily functions are completely normal. Most of the KLS cases are sporadic. At present, only 17 familial cases of KLS have been reported abroad, while domestic reports in China are rare. We analyzed the detailed medical history, laboratory examinations, differential diagnosis, and the disease prevalence amongst family members of a patient with familial KLS, in order to provide reference for the follow-up study of familial cases of KLS.

Objective To evaluate the effect of retention time of urokinase on hematoma dissipation in the treatment of severe ventricular hemorrhage by lateral ventricle drainage. Methods The clinical data of 62 patients with severe ventricular hemorrhage and having received bilateral ventriculostomy were retrospectively analyzed. These patients was divided into 3 groups according to the retention time of urokinase: A group (20 patients, retention time 1 h), B group (22 patients, retention time 2 h) , and C group (20 patients , retention time 3 h).The number of patients with complete hematoma dissipation at different time in each group were compared. Results At 5-6 d, 7-9 d and 10-12 d after operation, the number of hematoma dissipation in A group was 2, 5, 13 cases, in B group was 5, 13, 4 cases, and in C g group was 3, 13, 4 cases. The number of hematoma dissipation patients in three groups had significant difference (P=0.008), the number of hematoma dissipation patients between A group and B group, and between A group and C group had significant differences (P=0.005, 0.012), but there was no significant difference between B group and C group (P=0.621). The complication rate in three groups had no significant difference (χ2=2.540, P=0.281). Conclusions The 2 h retention time of urokinase is more suitable for the patients with severe ventricular hemorrhage who underwent external drainage.

Objective To observe the recent effect and safety of minimally invasive transurethral double pole plasma-prostatectomy (PKEP) for the treatment of the benign prostatic hyperplasia (BPH). Methods One hundred and twenty-six patients with BPH were selected by parallel group design, and divided into two groups by piecewise equilibrium stochastic method. Sixty-three patients in the control group were treated with transurethral prostate electrotomy (TURP). The study group of 63 patients was treated with PKEP. Weight, operation time, intraoperative bleeding and complications of the patients were recorded. Three months after surgery, the maximum urine flow rate (Qmax), residual urine volume (PVP), international prostate symptom score(IPSS)and quality of life score(QOL)was used to evaluate the improvement of symptoms. Results The average operation time, postoperative hospital stay, time placing a urinary catheter in study group was shorter than that in the control group(50.2 ± 8.5)min vs (62.4 ± 10.3)min,(5.0 ± 0.7)d vs.(6.4 ± 1.2)d,(38.4 ± 2.7)h vs.(80.5 ± 6.9)h,intraoperative blood loss was less than that in the control group, (62.4 ± 13.7)ml vs.(91.6 ± 23.5)ml,and removing tissue volume was better than that in the control group (53.4 ± 5.9) g vs. (39.6 ± 7.2) g. Differences were statistically significant (P < 0.05). After surgery, the PVP significantly reduced, Qmaxincreased significantly, the IPSS and QOL scores significantly reduced, and the differences were statistically significant(P<0.05). However, there was no significant difference between PVP, Qmax, IPSS and QOL in the two groups(P>0.05).The incidence of postoperative complications in the study was 30.16%(19/63), significantly lower than that of the control group(46.03%,29/63), and the difference was statistically significant(P<0.05). Conclusions PKEP is better than TURP in the treatment of large volume BPH of old age, and PKEP is safer than TURP.