OBJECTIVE To provide valuable insights for the adjustment of anti-infectious regimens， identification of adverse reactions， and individualized pharmaceutical care in patients with critically severe scrub typhus. METHODS Clinical pharmacists actively participated in the pharmaceutical care process for a patient with severe scrub typhus leading to mixed shock undergoing continuous renal replacement therapy and extracorporeal membrane oxygenation. Initially， the patient received meropenem （1 g， q12 h， ivdrip）， in combination with doxycycline （0.1 g， q12 h， po）， which was later switched to meropenem （1 g， q8 h， ivdrip） along with omacycline （100 mg， qd， ivdrip） due to impaired gastrointestinal function. However， as the patient’s condition progressively deteriorated and the infection became uncontrolled， the clinical pharmacists recommended that the clinicians adjust the anti-infective regimen to meropenem （2 g， q8 h， ivdrip） combined with tigecycline （100 mg for first dose； 50 mg， q12 h for maintenance； ivdrip）. The clinicians followed the advice of the clinical pharmacists. After treatment， the patient’s symptoms exhibited significant improvement， accompanied by a notable decrease in inflammatory markers， indicating that the infection had been successfully controlled. However， due to continuously increasing bilirubin levels， in order to reduce the risk of drug-induced liver injury， the clinicians changed tigecycline to azithromycin （0.5 g， qd， ivdrip） following the recommendation of the clinical pharmacists. RESULTS Ultimately， metagenomic next-generation sequencing of the bronchoalveolar lavage fluid and blood specimens indicated that Orientia tsutsugamushi had been completely eradicated in the patient. CONCLUSIONS Tigecycline may be a viable therapeutic choice for patients with severe scrub typhus. In the context of critically ill patients with scrub typhus， combining tigecycline with azithromycin might potentially enhance the efficacy in eliminating Orientia tsutsugamushi.

BACKGROUND:Liuwei Dihuang Wan takes"three tonifying and three reducing effects"as its compatibility feature to nourish yin and tonify the kidneys,while Zuogui Wan takes"seeking yin in yang"as its compatibility feature to nourish yin and tonify the kidneys by promoting yang.Both of them belong to the same method of nourishing yin and tonifying the kidneys,and have better curative effects at the symptomatic and cellular molecular levels. OBJECTIVE:To observe the effects of Liuwei Dihuang Wan and Zuogui Wan in bone metabolism,and to explore their mechanism of action in the osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)osteoblastic pathway. METHODS:Thirty-two Sprague-Dawley rats were randomized into model,Liuwei Dihuang Wan,Zuogui Wan,and sham operation group,with eight rats in each group.Osteoporosis models were prepared using removal of both ovaries in the first three groups.Starting at 30 days postoperatively,rats in the Liuwei Dihuang Wan group were gavaged with Liuwei Dihuang Wan 1.125 g/kg/d;rats in the Zuoqui Wan group were gavaged with Zuogui Wan 2.25 g/kg/d;and rats in the sham operation group and the model group were gavaged with saline 10 mL/kg/d.After 12 weeks of gavage,the rat tibia was taken to measure bone mineral density.The serum levels of estrogen,bone alkaline phosphatase,and cAMP/cGMP were measured using ELISA,and the expression of OPG/RANKL in the femur was detected using western blot. RESULTS AND CONCLUSION:Compared with the sham operation group,the model group showed a decrease in bone mineral density and levels of estrogen and bone alkaline phosphatase(P＜0.05)and an increase in cAMP/cGMP level(P＜0.05).Compared with the model group,the Liuwei Dihuang Wan group and the Zuogui Wan group significantly increased bone mineral density(P＜0.05)and bone alkaline phosphatase levels(P＜0.05);the Zuogui Wan group significantly decreased cAMP/cGMP levels(P＜0.05)and upregulated OPG expression(P＜0.05);the Liuwei Dihuang Wan group upregulated OPG expression and downregulated RANKL expression(P＜0.05);and both groups were unable to significantly increase estrogen levels(P＞0.05).To conclude,Zuogui Wan,which seeks yin from yang,can effectively increase the expression of OPG but cannot downregulate the expression of RANKL.However,Liuwei Dihuang Wan,which has three tonifying and three reducing effects,can bidirectionally regulate the expression of OPG and RANKL.This result suggests that Liuwei Dihuang Wan can significantly inhibit osteoclastic function compared with Zuogui Wan,and further research is needed to verify this conclusion.

BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Oral health is closely related to facial aesthetics, mastication, pronunciation, and systemic diseases. Flexible sensors can improve current deficiencies in clinical diagnosis and treatment through oral health monitoring. This paper reviews the research on and application of flexible sensors in oral health monitoring in recent years, providing a reference for the further development of flexible sensors in the oral field. The structural basis of flexible sensors includes a flexible substrate, stretchable electrodes, and an active layer, and each part is designed through material selection to adapt to the oral environment. The sensing mechanisms of sensors involve electricity, optics, electrochemistry, and immunology, among which electro-chemical, biological, and optical sensors are particularly prominent in the oral field. The monitored signals include physical signals such as orthodontic force, bite force, respiratory humidity, and implant temperature; chemical signals such as saliva metabolites and oral gases; and biological signals such as periodontal disease and oral cancer markers. At present, flexible sensors still face many challenges in this special oral environment. Future research directions include improving the biocompatibility, moisture resistance, and flexible fitting ability of sensors in the oral cavity; using temperature-insensitive materials and protective films to improve stability; and introducing artificial receptors and sensor arrays to improve factors such as selectivity. In addition, multi-disciplinary cooperation is crucial for breaking through current bottlenecks and achieving more accurate disease diagnosis and health monitoring. In the field of stomatology, finding specific biomarkers related to corresponding oral diseases is the key to sensor health monitoring. Through these efforts, flexible sensors are expected to gain more extensive applications in the field of oral health monitoring.

The construction of healthy schools is one of the key measures to implement the Outline of the Healthy China 2030 Plan. The establishment and implementation of the Guidelines for Healthy Primary and Secondary School Evaluation （Guidelines） is helpful for the large-scale promotion and standardization of healthy school construction by government departments in Shanghai and other major cities in China， thereby more students benefited from the Healthy China Initiative. The Guidelines integrate the efforts of multiple departments related to school health， based on internationally recognized content and strategies for health-promoting schools. They aim to foster students’ health development by combining the basic requirements for school health with priority projects for health promotion. Healthy school evaluation indicators and standardized requirements suitable for the current socio-economic development level of Shanghai have been developed， aligning with international concepts of health-promoting schools. They also reflect a high starting point and high level of investment and development in school health in Shanghai over the past decade. The Guidelines provide recommendations on the basic requirements， organization guarantees and management， social and culture environment， health promotion education， health services， and connection between school and communities， and families， of healthy school evaluation for primary and secondary schools. This paper aims to interpret the compilation process and main content of the Guidelines.

Objective:To observe the effects of Zhulian stimulant type Ⅰ acupuncture on the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB and tissue homogenate cyclic adenosine phosphate (cAMP) in rats with diabetic bladder (DCP); To explore the mechanism of Zhulian stimulant type Ⅰacupuncture on DCP.Methods:Totally 50 SD rats were divided into control group, model group, Western medicine group, ordinary acupuncture group, Zhulian stimulant type Ⅰ acupuncture treatment group (acupuncture treatment group) according to random number table method, with 10 rats in each group. DCP rat model was prepared by intraperitoneal injection of streptozotocin (STZ), except for the control group. The Western medicine group was given mecobalamine for gavage; acupoints of "Zhongji", "Sanyinjiao", "Liechou" and "Taichong" were selected. The ordinary acupuncture group was treated with ordinary acupuncture technique, and the acupuncture treatment group was treated with Zhulian stimulant type Ⅰ acupuncture, 1 time/d, 30 minutes/time. Samples were taken after 4 weeks of treatment. The maximum bladder volume, residual urine volume and wet weight of the bladder were detected. The morphology of rat bladder was observed by HE staining. The expression level of BDNF was detected by immunohistochemistry. The expression of cAMP was detected by Western blot. The level of TrkB was determined by ELISA. Real-time fluorescence quantitative PCR (RT-PCR) was used to detect the mRNA expressions of BDNF and cAMP.Results:Compared with model group, maximum bladder volume, residual urine volume and wet weight of bladder in Western medicine group, ordinary acupuncture group and acupuncture treatment group decreased ( P<0.01), and those in Western medicine group and acupuncture treatment group were lower than those in ordinary acupuncture group ( P<0.01). The expressions of BDNF mRNA and protein, cAMP mRNA and protein in Western medicine group, ordinary acupuncture group and acupuncture treatment group increased ( P<0.05), and the level of TrkB increased, and the Western medicine group and acupuncture treatment group were higher than that in ordinary acupuncture group ( P<0.05). Conclusions:Zhuliping stimulant type Ⅰ acupuncture has a protective effect on the bladder function of diabetic rats. The mechanism may be related to the up-regulation of BDNF and mRNA, TrkB, cAMP and mRNA expressions.

Background Shoemaking industry workers are prone to work-related musculoskeletal disorders (WMSDs) due to long-term awkward postures during the work process. There is little research on the prevalence and influencing factors of WMSDs in the knee region of this industry, and it should be taken seriously. Objective To estimate the prevalence of work-related knee pain among shoemaking workers and analyze the related influencing factors. Methods A total of 6982 shoemaking workers were selected from 26 shoemaking factories in Guangdong, Hubei, Fujian, Chongqing, Shandong, Zhejiang, and Jingxi by convenience sampling. Prevalence of work-related knee pain in past year, demographic characteristics, occupational related factors, and work posture were collected by a cross-sectional survey using the electronic version of Musculoskeletal Disorder Questionnaire. Logistic regression analysis was used to analyze the influencing factors that may lead to work-related knee pain. Results This survey collected 6982 valid questionnaires with a recovery rate of 98.3%. The prevalence of work-related knee pain of shoemaking workers in the past 12 months was 13.0% (908/6982). According to the results of logistic regression analysis, compared with workers with less than 5 years of service, workers with 5-10 years of service (OR=1.21, 95%CI: 1.02, 1.45) and more than 10 years (1.53, 95%CI: 1.27, 1.83) showed a higher risk of knee WMSDs; sometimes, often and very frequent (reference : rarely or never) long-term standing (OR=1.33, 95%CI: 1.08, 1.64; OR=2.67, 95%CI: 2.10, 3.39; OR=2.75, 95%CI: 2.08, 3.63) and sometimes, often and very frequent (reference: rarely or never) long-term squatting or kneeling (OR=1.80, 95%CI: 1.47, 2.21; OR=2.43, 95%CI: 1.58, 3.75; OR=3.22, 95%CI: 1.66, 6.24) increased the risk of knee pain: long-term bending (OR=1.59, 95%CI: 1.34, 1.89) and often repeated movement of lower limbs and ankles (OR=1.48, 95%CI: 1.25, 1.75) were also risk factors for knee WMSDs among shoemaking industry workers (P<0.05). Adequate rest time (OR=0.58, 95%CI: 0.49, 0.68) and able to stretch or change leg posture (OR=0.75, 95%CI: 0.64, 0.88) reduced the risk of knee WMSDs (P<0.05). Conclusion In the shoemaking industry, length of service and awkward postures are risk factors for knee pain. The shoemaking enterprises should ensure that workers have sufficient rest time, reduce long-term standing, squatting, kneeling, and bending postures, as well as lower limbs repetition in order to reduce the occurrence of knee WMSDs of workers.

BACKGROUND:The mechanisms and targets of alendronate in the treatment of osteoporosis still need to be investigated in depth. OBJECTIVE:To investigate the mechanism by which alendronate regulates bone metabolism in rats with osteoporosis and to perform a bioinformatics analysis of differentially expressed proteins. METHODS:Female Sprague-Dawley rats were randomly divided into three groups(n=12 per group):model group,alendronate group and sham-operated group.Animal models of osteoporosis were prepared using ovariectomy in the model and alendronate groups.At 4 weeks after modeling,rats in the alendronate group were gavaged with alendronate;the other two groups were given the equal volume of normal saline.After 12 weeks of continuous gavage,the bone mineral density of the tibia was measured and the lumbar spine of the rats was taken for proteomic analysis using Tandem mass tag-liquid chromatography-tandem mass spectrometry technique to identify differentially expressed proteins for gene ontology,Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis. RESULTS AND CONCLUSION:There were 32 up-regulated proteins and 51 down-regulated proteins identified between the alendronate group and model group.Gene ontology enrichment analysis showed that the differentially expressed proteins were mainly involved in molecular functions,such as binding and catalytic activity,and in biological processes,such as cellular process and metabolic process.Kyoto Encylopedia of Genes and Genomes enrichment analysis showed that the differentially expressed proteins in the alendronate group and model group were mainly involved in the biosynthesis of pantothenate and coenzyme A.Protein-protein interaction analysis indicated that among the differentially expressed proteins in the alendronate group and model group,Hspa1l,Enpp3,Unc45a,Myh9 and Cant1 were located at the nodes of the protein-protein interaction network and were closely related to bone metabolism.Overall,these findings indicate that alendronate may regulate bone metabolism in the rat model of osteoporosis by regulating the expression of differentially expressed proteins and biosynthesis of pantothenate and coenzyme A.

BACKGROUND:Hyperhomocysteinemia is closely related to the function of islet β cells,but its specific molecular mechanism is not fully understood. OBJECTIVE:To investigate the role of N6 methyltransferase-like 3(METTL3)in homocysteine(Hcy)-induced autophagy of mouse islet β cells. METHODS:The 3rd and 4th generation mouse islet β cells were taken for the experiment.(1)Cell modeling and grouping:cells in control group were not treated with Hcy,while those in homocysteine group were treated with 100 μmol/L Hcy for 48 hours.(2)The mouse islet β-cells were transfected with the plasmids overexpressing Ad-METTL3 and si-METTL3 according to the instructions of LipofectamineTM 2000.Three different interfering fragments were designed,and the one with the best interfering efficiency was verified and screened by PCR.(3)After transfection,the cells were divided into control group,Hcy group,Ad-NC(negative control)+Hcy group,Ad-METTL3+Hcy group,si-NC(negative control)+Hcy group and si-METTL3+Hcy group.(4)qRT-PCR and western blot were used to detect the expression levels of METTL3 and autophagy-related proteins LC3Ⅱ/Ⅰ and p62 in cells.Insulin level was determined by ELISA to evaluate insulin secretion capacity of islet cells.Autophagy-related proteins and insulin level were detected after overexpression and interference with METTL3. RESULTS AND CONCLUSION:Compared with the control group,the expression level of LC3Ⅱ/Ⅰ was increased(P＜0.05),the expression of p62 was significantly reduced(P＜0.05),and the insulin secretion capacity was significantly decreased(P＜0.05)in the Hcy group.Compared with the control group,the protein and mRNA levels of METTL3 were reduced in the Hcy group(P＜0.05).After METTL3 silencing in islet β cells,Hcy further upregulated the expression of LC3Ⅱ/Ⅰ(P＜0.05),significantly dowregulated the expression of p62(P＜0.05),and increased the insulin level(P＜0.05).After overexpression of METTL3,Hcy significantly decreased the LC3Ⅱ/Ⅰ expression and increased the p62 expression in islet β cells(P＜0.05).To conclude,METTL3 is involved in the Hcy-induced autophagy regulation of islet β cells and plays a role in the regulation of insulin secretion.

Objective:To establish contact dermatitis pruritus model and detect itch,anxiety and depression-like behaviors.To observe the activation of the medial prefrontal cortex(mPFC)neurons and provide morphological evi-dence for its involvement in the regulation of itch perception information.Methods:A model of contact dermatitis pruri-tus was constructed with diphenylcyclopyrenone(DCP)applied on the neck and back of the mouse,and the itch per-ception video tracking system was used to detect the scratching behavior.Open field and suspended tail behavioral ex-periments were conducted to explore the anxiety and depression-like behaviors of mice under contact dermatitis.The dis-tribution of c-Fos and p-ERK1/2 positive cells in the mPFC of contact dermatitis model mice was investigated by immu-nofluorescence staining.Results:The contact dermatitis pruritus model was successfully established,and the bouts of scratching in the contact dermatitis model group was significantly higher than that in the control group(P＜0.05).The results of open field test showed that the time and distances were significantly reduced in the central area of the contact dermatitis model group.The results of the tail suspension experiment suggested that the time of immobility increased sig-nificantly in the contact dermatitis model group(P＜0.05).There were more c-Fos positive and p-ERK1/2 positive cells in the mPFC compared with the control group(P＜0.05).Conclusion:Bouts of scratching were increased in the contact dermatitis group and the mice had anxiety and depression-like behaviors.In the contact dermatitis state,mPFC neurons were activated,providing morphological evidence for the involvement of mPFC neurons in contact dermatitis pruritus and accompanying affective disorders such as anxiety and depression.