The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.

Purpose/Significance To design a comprehensive data platform to meet the needs of collecting and sharing survey data on meteorological sensitive diseases,so as to enhance monitoring capabilities for meteorological sensitive diseases in China.Method/Process Through various methods such as data extraction,data exchange,data import and customized collection,disease data,meteoro-logical data,environmental data and diagnosis and treatment data are processed and integrated into the platform for unified management.Result/Conclusion This platform realizes the functions of data collection,aggregation,visualization display and data sharing,which can provide support for scientific researchers in various bases across the country to better manage and utilize meteorological sensitive disease survey data.

Objective:To explore the clinical characteristics, treatment regimens and prognostic influencing factors of patients with multiple myeloma (MM) involving central nervous system (CNS).Methods:The clinical data of 18 MM patients involving CNS in Second Affiliated Hospital of Naval Medical University from January 2014 to June 2020 were retrospectively analyzed. Their clinical characteristics, treatment and prognosis were also analyzed. Kaplan-Meier method was used to make survival analysis and log-rank was performed; Cox proportional risk model was used to make univariate and multivariate analysis.Results:The cohort of 18 patients included 12 males and 6 females; the median age of patients involving CNS was 54 years (38-71 years). The median time from diagnosis to the involvement of CNS was 22 months (0-126 months).Among 18 patients, 1 case was primary MM involving CNS, and 17 cases were secondary MM involving CNS. All patients had Durie-Salmon (DS) stage Ⅲ; 10 cases had international staging system (ISS) stage Ⅲ, 6 cases had ISS stage Ⅱ, and 2 cases had ISS stage Ⅰ. Involvement sites of CNS included 7 cases of involving the dura mater alone and 4 cases of involving the pia mater alone, 2 cases of involving brain parenchyma and 5 cases of involving both meninges and brain parenchyma. The most common neurological symptoms were headache and cranial nerve palsy, and 9 patients had multiple neurological symptoms. All patients received systemic therapy, 16 patients received an intrathecal injection and/or radiotherapy; and the overall effective rate was 66.7%, including 3 achieving strict complete remission (sCR), 1 achieving complete remission (CR), 3 achieving very good partial remission (VGPR), 5 achieving partial remission (PR). The median overall survival (OS) was 32.7 months. Counting from the point of CNS involvement, the median progression-free survival (PFS) and OS time was 7.5 months, 12.2 months, respectively. The median PFS of MM patients in the dura-involved alone group was longer than that in the non-dura-involved alone group (15.1 months vs. 5.9 months, P = 0.009); the median OS of MM patients in the dura-involved alone group was longer than that in the non-dura-involved alone group (16.9 months vs. 10.7 months, P = 0.175). Multivariate Cox analysis showed that dura mater involvement alone was an independent factor affecting PFS in MM patients with CNS involvement ( HR = 0.191,95% CI 0.038-0.952, P = 0.043). Conclusions:MM involving CNS is rarely found and has a very poor prognosis. Different sites of CNS involvement could affect the prognosis of patients. There is a lack of effective treatment regimens.

Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local/drug therapy*

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Conventional therapies for hemophilia A (HA) are prophylactic or on-demand intravenous FVIII infusions. However, they are expensive and inconvenient to perform. Thus, better strategies for HA treatment must be developed. In this study, a recombinant FVIII cDNA encoding a human/rat hybrid FVIII with an enhanced procoagulant potential for adeno-associated virus (AAV)-delivered gene therapy was developed. Plasmids containing human FVIII heavy chain (hHC), human light chain (hLC), and rat light chain (rLC) were transfected into cells and hydrodynamically injected into HA mice. Purified AAV viruses were intravenously injected into HA mice at two doses. Results showed that the hHC + rLC protein had a higher activity than the hHC + hLC protein at comparable expression levels. The specific activity of hHC + rLC was about 4- to 8-fold higher than that of their counterparts. Hydrodynamic injection experiments obtained consistent results. Notably, the HA mice undergoing the AAV-delivered hHC + rLC treatment exhibited a visibly higher activity than those treated with hHC + hLC, and the therapeutic effects lasted for up to 40 weeks. In conclusion, the application of the hybrid FVIII (hHC + rLC) via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice. These data might be of help to the development of optimized FVIII expression cassette for HA gene therapy.
Animals ; Dependovirus/genetics* ; Factor VIII/metabolism* ; Genetic Therapy/methods* ; Hemophilia A/therapy* ; Humans ; Mice ; Rats

Objective:To establish the normal reference value of lumbar bone mineral density (BMD) under quantitative CT (QCT) in Chinese healthy adult females and to explore the regional differences.Methods:Total of 35 431 healthy women who met the inclusion criteria of Chinese health quantitative CT big data program were selected in this study. The BMD of the central plane of L 1 and L 2 vertebrae was measured by Mindways′s QCT system, and the mean value was taken. One-way analysis of variance was used to compare the BMD differences of lumbar vertebrae in women of different ages and regions. The subjects were grouped by an age interval of 10 years, and the level of BMD in different regions of the same age group were compaired. Results:The peak BMD of Chinese healthy adult women appeared in the age group of 20-29 years (Northeast China(183.01±24.58) mg/cm 3, North China (188.93±24.80) mg/cm 3, East China (187.54±27.71) mg/cm 3, South China (186.22±33.72) mg/cm 3, Central China (176.33±24.91) mg/cm 3, Southwest China(182.25±28.00) mg/cm 3), and then it decreased with age. The level of BMD in different regions decreased with the age. Before the age of 70 years, BMD in Central and Southwest China was always at a low level((176.23±24.91) to (90.38±28.12) mg/cm 3, 182.25±28.00 to (88.55±25.68) mg/cm 3), lower than those in Northeast China ((183.01±24.58) to (99.69±27.85) mg/cm 3), North China ((188.93±24.80) to (95.89±26.12) mg/cm 3), East China ((187.54±27.71) to (95.65±27.86) mg/cm 3). After 70 years of age, BMD tended to be the same in different regions ( P>0.05). The BMD values in Central China and Southwest China were similar in the age group of 40-60 years ( P>0.05). The BMD values in the health adult femles in the age group of 60 years in different regions of Chinawere all lower than those of bone mass abnormality (all P<0.05). The detection rate of osteoporosis in females over 50 years was the highest in Southwest China (25.65%) and it was the lowest in North China (17.30%). Conclusions:This study establishes reference values of BMD under QCT in healthy Chinese women, which can be used as a reference basis for identifying women with low BMD who are at risk of osteoporosis. The BMD value is the lowest in Southwest China and the highest in South China.

Objective:To explore the clinical efficacy of microsurgical technique combined with cosmetic suture technique in situ replantation of total scalp avulsion.Methods:The clinical data of patients with total scalp avulsion admitted to the Department of Burn and Plastic Surgery of General Hospital of Northern Theatre Command from January 2015 to December 2020 were collected. All patients were treated by microsurgical technique combined with cosmetic suture technique. Thorough debridement was performed during the operation. Active anti-shock treatment was given to the patient with hemorrhagic shock. The vascular was explored and labeled. The vascular anastomosis was conducted by microsurgical technique. The venous anastomosis was performed in the first place. The arterial anastomosis was performed according to the patient's condition. Symptomatic treatment, such as routine anti-coagulation, was given to patients after the operation. An infection prevention strategy was performed in patients. The recovery of patients was observed.Results:A total of six patients were involved in this study. All patients were females, aged from 36 to 55 years old. Various degrees of wound contamination can be seen, and one patient with hemorrhagic shock. The superficial temporal vein, supraorbital vein and sentinel vein were anastomosed in two patients, and the superficial temporal vein and sentinel vein were anastomosed in four patients. The superficial temporal artery and supratrochlear artery were anastomosed in two patients, and the superficial temporal artery was anastomosed in four patients. All patients were followed up for 3 months to 2 years, averaging 13.71 months. More than 90% of the scalp survived in three patients, 80% in two patients, and 50% in one patient. The necrotic area survived after replantation of a split-thickness skin graft. The sensory function of surviving scalp after replantation was slightly regressed. The hair growth was normal. Only superficial linear scar left. All patients were satisfied with the efficacy.Conclusions:The application of the microsurgical technique for vascular anastomosis combined with cosmetic suture technique for repair can achieve good clinical efficacy in situ replantation of total scalp avulsion.

Objective:To explore the clinical efficacy of microsurgical technique combined with cosmetic suture technique in situ replantation of total scalp avulsion.Methods:The clinical data of patients with total scalp avulsion admitted to the Department of Burn and Plastic Surgery of General Hospital of Northern Theatre Command from January 2015 to December 2020 were collected. All patients were treated by microsurgical technique combined with cosmetic suture technique. Thorough debridement was performed during the operation. Active anti-shock treatment was given to the patient with hemorrhagic shock. The vascular was explored and labeled. The vascular anastomosis was conducted by microsurgical technique. The venous anastomosis was performed in the first place. The arterial anastomosis was performed according to the patient's condition. Symptomatic treatment, such as routine anti-coagulation, was given to patients after the operation. An infection prevention strategy was performed in patients. The recovery of patients was observed.Results:A total of six patients were involved in this study. All patients were females, aged from 36 to 55 years old. Various degrees of wound contamination can be seen, and one patient with hemorrhagic shock. The superficial temporal vein, supraorbital vein and sentinel vein were anastomosed in two patients, and the superficial temporal vein and sentinel vein were anastomosed in four patients. The superficial temporal artery and supratrochlear artery were anastomosed in two patients, and the superficial temporal artery was anastomosed in four patients. All patients were followed up for 3 months to 2 years, averaging 13.71 months. More than 90% of the scalp survived in three patients, 80% in two patients, and 50% in one patient. The necrotic area survived after replantation of a split-thickness skin graft. The sensory function of surviving scalp after replantation was slightly regressed. The hair growth was normal. Only superficial linear scar left. All patients were satisfied with the efficacy.Conclusions:The application of the microsurgical technique for vascular anastomosis combined with cosmetic suture technique for repair can achieve good clinical efficacy in situ replantation of total scalp avulsion.

Objective:To investigate the treatment options for multiple myeloma patients with central nervous system involvement (CNS-MM) , as well as their clinical characteristics and prognostic factors.Methods:Between January 2011 and January 2022 our center diagnosed 18 people with CNS-MM. A retrospective analysis was done on the clinical information from the initial diagnosis and central nervous system involvement, and it was compared to 1∶3 matched newly diagnosed MM from the same period. Analysis was done on the clinical characteristics and survival rates of the two groups.Results:In patients with CNS-MM, the median time of onset was 14.2 (0.9-79.6) months and the median overall survival (OS) was 30.5 months from initial diagnosis and only 3.8 months in patients after CNS involvement. The CNS-MM patients showed more IgD type ( P=0.010) , severer anemia ( P=0.014) , a higher proportion of bone marrow plasma cells ( P=0.013) , more extramedullary lesions ( P=0.001) , and increased lactic dehydrogenase (LDH) ( P=0.009) when compared to the control group. Lenalidomide or pomalidomide-based combinations had higher rates of hematology and CNS remission than bortezomib or daratumumab-based regimens (75.0% vs 16.7% , P=0.019) . Patients who received IMiD-based regimens and had 2 high-risk factors at initial diagnosis (high LDH and extramedullary lesions) had a significantly lower incidence of CNS-MM ( P=0.026) . At the initial diagnosis, LDH ( P=0.008, HR=7.319, 95% CI 1.663-32.219) and extramedullary lesions ( P=0.006, HR=8.054, 95% CI 1.828-35.486) were independent risk factors for the occurrence of CNS-MM. Conclusion:Patients with CNS-MM had a poor prognosis. Patients with high LDH or extramedullary lesions at the time of the initial diagnosis are more likely to have CNS-MM. The prognosis of this patient may be improved by immunoregulator-based therapy.