Drug testing involves many analytical instruments and test items, sample pretreatment is tedious, the industry's intelligence level remains low, making drug testing a labour-intensive job. However, in the era of Industry 4.0 intelligent manufacturing, intelligent transformation of the quality control (QC) laboratory has become the focus of industry. At the same time, driven by consistency evaluation of the quality and efficacy of generic drugs and the centralized procurement policies, pharmaceutical companies have intensified their competition, further stimulating the intrinsic demand for laboratory intelligence. Based on the current state and future trends of the pharmaceutical industry, this review discusses the development of a digital and automated QC laboratory. It points out the necessity of transitioning from the traditional centralized laboratory model to an intelligent, distributed quality control model to accommodate continuous manufacturing processes. At the same time, it also analyses the potential challenges in the implementation process and coping strategies, in order to provide relevant practitioners with ideas for building intelligent QC laboratories.

Objective To describe MRI findings of acute spinal cord decompression sickness.Methods MRI findings of 5 cases with clinical definite acute spinal cord decompression sickness were retrospectively analyzed.The main clinical informations included underwater performance history against regulations,short-term complete or incomplete spinal cord injury symptoms after fast going out of water,sensory disability and urinary and fecal incontinence,etc.Results Spinal cord vacuole sign was found in all 5 cases.Iso-signal intensity(n=3),high signal intensity(n=1),and low signal intensity (n=1)was demonstrated on T1 WI,and high signal intensity(n=5)was found on T2 WI.Owl eye sign was detected in 3 cases,and lacune foci were seen in 2 cases.Conclusion MRI findings of acute spinal cord decompression sickness had some characteristics,and it was easy to diagnose by combining diving history with clinical manifestations.

BACKGROUND:There is a lack of the research concerning the biocompatibility of nano-hydroxyapatite/polyphenylene sulfide (nHA/PPS) composites.OBJECTIVE:To evaluate the in vivo biocompatibility of nHA/PPS composites based on the completed research in vitro.METHODS:Systemic toxicity test:Sprague-Dawley rats were given the intraperitoneal injection of nHA/PPS extract or normal saline.The general situation,body mass and the histological changes of the liver and kidney were observed at 72 hours after injection.Delayed type hypersensitivity test:nHA/PPS extract or normal saline was injected subcutaneously into the back of the rats.Afterwards,skin irritation symptoms were observed at 72 hours.Local reaction experiment:nHA/PPS composites and polyethylene were respectively implanted into the back of the rats.The pathological changes of the implanted materials and their surrounding tissues were observed at 15 and 30 days after implantation.RESULTS AND CONCLUSION:(1) The rats were in good situation after nHA/PPS injection;the body mass increased steadily,which showed no significant difference from the control group (P ＜ 0.05);the morphology and color of the liver and kidney were normal,and the systemic toxicity of the composite materials was normal according to the degree of toxicity classification.(2) There were no obvious skin irritation symptoms after the subcutaneous injection of nHA/PPS composites,and the primary irritation index was less than 0.4,suggesting a low hypersensitivity.After implantation of nHA/PPS composites,there was no obvious degradation,absorption and rejection,and both the degree of inflammatory reaction (15 days ≤ level Ⅲ,30 days ≤ level Ⅱ) and the thickness of fibrous capsule (15 days ≤ level Ⅲ,30 days ≤ level Ⅱ) revealed the good biocompatibility of the composites.These results suggest that the nHA/PPS composites hold an excellent biocompatibility in vivo.

Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L⁻¹ permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L⁻¹ permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L⁻¹ permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L⁻¹ permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L⁻¹ permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L⁻¹ compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L⁻¹ permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L⁻¹ permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L⁻¹ permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L⁻¹ permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

Adult ; Biopsy ; Female ; Graft Rejection ; pathology ; Humans ; Intestinal Mucosa ; pathology ; Intestine, Small ; injuries ; pathology ; transplantation ; Male ; Organ Transplantation ; adverse effects ; Reperfusion Injury ; etiology ; pathology ; Young Adult

Diving medicine is one of the branches of military medicine, and plays an important role in naval development. This review introduces the progress of researches on undersea and hyperbaric physiology and medicine in the past few years in China. The article describes our research achievement in conventional diving and its medical support, researches on saturation diving and its medical support, submarine escape and its medical support, effects of hyperbaric environments and fast buoyancy ascent on immunological and cardiological functions. Diving disorders (including decompression sickness and oxygen toxicity) are also introduced.
China ; Decompression Sickness ; Diving ; physiology ; Humans ; Military Medicine ; Submarine Medicine

Objective To identify risk factors for a human orf disease outbreak in a village in Chongqing city. Methods Standardized case-definition was set and a case-finding program was conducted among all the residents of the village. All the patients were interviewed using a standardized questionnaire and collected fluids in the skin rash for laboratory testing. A retrospective cohort investigation was conducted among all the village residents who introduced the black goats to analyze the risk of orf infection, in relation to the mode and frequency of contacts to the infected goats. Results We found 18 cases (including 16 suspected cases and 2 confirmed cases) among the members of 10 families that introduced the black goats. Village residents who had ever used their legs to grip the goats were nearly five times as likely to develop orf disease as those who did not (RR=4.98, 95％CI: 1.34-75.27). Village residents who had ever washed and wiped the goats were three times as likely to develop orf disease as those who had not (RR = 3.09,95％CI: 0.98-45.38). The frequency of contacts with the infected goats was associated with the risk of developing orf disease in a dose-response fashion (x2 test for trends: P= 0.006).Frequently wearing long trousers when dealing with the goats appeared as a protective factor (RR=0.30,95％CI: 0.15-0.78). Conclusion This outbreak was caused by the introduced black goats which carried and infected by the orf virus. Direct physical contact with infected goats but without wearing protective clothing were risk factors for the development of human orf disease.

Objective To investigate the current status of endemic fluorosis in Shandong province, and to provide the scientific evidence for making strategies for prevention and control of the disease. Methods According to "The National Technical Scheme for Endemic Disease Control in 2008", thirty-four counties were divided into mild, moderate and severe endemic fluorosis areas and a village was randomly selected from each category of the area to carry out the monitoring of endemic fluorosis. The content of fluoride in drinking water and urine was determined by F-ion selective electrode, dental fluorosis of children aged 8 to 12 was diagnosed by Dean method and skeletal fluorosis diagnosed by clinic and X-rays. Results The monitoring was done in 70 water-improving villages in 34 counties, among which 54 villages had water fluoride content ≤ 1.00 mg/L and accounted for 77.14%(54/70), 16 villages had water fluoride content ＞ 1.00 mg/L and accounted for 22.86%(16/70), the highest water fluoride content was 4.46 mg/L. The monitoring was also carried out in 32 non-water-improving villages in 34 counties, among which 9 villages had water fluoride content ≤ 1.00 mg/L and accounted for 28.12%(9/32), 23 villages had water fluoride content ＞ 1.00 mg/L and accounted for 71.88% (23/32), the highest water fluoride content was 4.09 mg/L. The total rate of dental fluorosis of children aged 8 to 12 was 45.81%(1988/4340), the index of dental fluorosis was 0.97 and the rate of dental damage was 6.91%(300/4340). The urinary fluoride values above 1.40 mg/L were found in 55.33%(1417/2657) of children aged 8 to 12, with the highest urinary fluoride concentrations was 18.53 mg/L. The rate of skeletal fluorosis by clinic and X-rays in adults older than 16 years were 4.25% (2462/57 968) and 28.40%(23/81 ), respectively. The urinary fluoride values above 1.60 mg/L were found in 55.86% (1130/2023) of adults older than 16 years, with the highest urinary fluoride concentrations was 25.44 mg/L. Conclusions Endemic fluorosis in Shandong province has not yet been effectively controlled,control situation is still grim. Prevention efforts need to be further strengthened.

Objective To explore the association between total cholesterol and type 2 diabetes ( T2DM) ． Methods Non－diabetic people who aged 20 to 90 years at the baseline and who had physical examination more than 2 times were screened． Comparisons of the baseline characteristics were conducted with Student－t test or Pearson chi－square test． Generalized estimating equation ( GEE) was used to analyze the effect of total cholesterol of quantiles groups ( 2．10－ mmol /L，4．16－ mmol /L，4．76－ mmol /L and 5．42 －13．29 mmol /L) to type 2 diabetes． Results The cohort with an average age of 3．53 years per person in- cluded 12 928 subjects and 45 626 person－years． During the follow－up，447 cases of new－onset diabetes occurred and the incidence density was 9. 80‰． The high incidence of type 2 diabetes increased with the increase of total cholesterol． After adjusting the factors including age，high density lipoprotein，hypertension and obesity，based on the 2. 10－ mmol /L group，the relative risk ( RR) of the 4. 16－ mmol /L，4. 76－ mmol/L and 5. 42－13. 29 mmol /L group were 1. 24( 95% CI: 0. 83－1. 86) ，1. 75 ( 95% CI: 1. 19－2. 56) and 3. 60( 95% CI: 2. 51－5. 17) ，respectively． Conclusions Total cholesterol is associated with type 2 diabetes，and as the total cholesterol increases，the risk of developing type 2 diabetes increases．

Objective To assess the efficacy and adverse-event profile of monotherapy oradd-on therapy with topiramate in elderly patients with epilepsy. Methods A multicenter, prospective,open-label, observational study of topiramate, for either monotherapy or add-on therapy, was performedamong 119 elderly patients with epilepsy in the Outpatient Department of Neurology of 52 generalhospitals in China. After the baseline evaluation, topiramate was given at the target dose of 200 mg/dayover an 8-week titration period. In the subsequent 12-week maintenance period, the topiramate dose wasadjusted (200-300 mg) according to the clinical results. The patients were followed up for 6 months, withmonthly visits and regular physical, neurological and laboratory examinations. Results After themaintenance period, 106 patients (89.1%) showed a seizure frequency reduction by 50% or greater fromthe baseline, among whom 65 patients(93.8%)received the monotherapy and 54(83.8%) had the add-ontherapy. Topiramate monotherapy and add-on therapy resulted in a complete seizure control in over 50%of the patients with various types of seizure. In patients with disease course less than 1 year, between 1and 3 years, between 4 and 6 years, and over 6 years, topiramate monotherapy resulted in seizurereduction by 92.86%, 91.67%, 100%, and 94.44%, and the add-on therapy reduced the seizure by80.00%, 85.71%, 70.00%, and 86.36%, respectively. When combined with carbamazepine, valproatesodium, phenytoin, phenol barbital, and diazepam, the total effective rate oftopiramate was 79.41%,87.50%, 85.71%, 0%, and 80.00%, respectively. Topiramate, especially in monotherapy, caused onlymild or moderate adverse effects. Conclusion Topiramate is effective and safe for either monotherapyor add-on therapy of epilepsy in elderly patients. The types of epilepsy, disease course, or the drugs usedin the add-on therapy do no obviously affect the efficacy of topiramate for seizure control.