Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
Animals ; Nerve Tissue Proteins/metabolism* ; Mice, Knockout ; Dendrites/metabolism* ; Mice ; Synapses/metabolism* ; Gyrus Cinguli/metabolism* ; Male ; Mice, Inbred C57BL ; Autism Spectrum Disorder/genetics* ; Microfilament Proteins

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Objective To analyze the distribution and drug resistance patterns of pathogenic bacteria in bile and blood cultures obtained from patients with biliary stones accompanied by acute biliary tract infection,to evaluate the clinical appropriate-ness of antibiotic use based on drug sensitivity results,and to provide evidence for empirical antibiotic treatment in such patients.Methods The clinical data of 161 patients with biliary calculi complicated by acute biliary tract infection who were admitted to the First People's Hospital of Neijiang from 2017 to 2023 were retrospectively analyzed.The results of microbial culture,drug sensitivity analysis,and patient characteristics were assessed to evaluate the appropriateness of clinical antimicrobial therapy.Results Among the 161 patients with positive cultures,212 strains of pathogenic bacteria were detected.The predominant patho-gens were Escherichia coli,Klebsiella pneumoniae subspecies,and Enterococcus faecium.Age and underlying diseases significantly affected the distribution of Escherichia coli and Klebsiella pneumoniae subspecies.Within the gram-negative bacterial group,Esche-richia coli and Klebsiella pneumoniae subspecies exhibited higher drug resistance to commonly used broad-spectrum penicillin,third-generation cephalosporin and quinolones but lower resistance rates to piperacillin and tazobactam;furthermore,elderly indi-viduals aged ≥65 years showed higher resistance rates to ceftriaxone than those under age 65 while people with drug exposure history had higher ceftazidime resistance rates that were statistically significant.In contrast to Enterococcus faecalis which displayed low antimicrobial resistance rates for most drugs tested in this study,Enterococcus faecium demonstrated high levels of antibiotic resistance;however,both Enterococcus faecalis and Enterococcus faecium exhibited zero-resistance rates against vancomycin and tigecycline although this may be attributed to their small sample size in our study cohort.Finally,we found that empirical anti-in-fective drugs,as well as target anti-infective drugs,were not prescribed rationally among these patients due mainly to inappropriate combinations of antibiotics or incorrect dosages.Conclusions The predominant pathogens in patients with acute biliary tract infection are gram-negative bacteria,Gram-positive bacteria,and fungi;however,the potential involvement of anaerobic bacteria should not be overlooked.Vancomycin exhibits sensitivity against gram-positive bacteria,yet the overall rationality of antibiotic usage remains suboptimal.Enhanced clinical testing for pathogenic microorganisms is imperative in the management of biliary stones accompanied by acute biliary tract infection.In contrast,clinical pharmacists should provide comprehensive training on anti-infective drugs to clinicians to facilitate their judicious selection of antibiotics based on drug sensitivity results and prevent the e-mergence of multidrug-resistant bacteria.

Mild cognitive impairment due to Alzheimer′s disease is an inevitable pathological stage in the early development of Alzheimer′s disease, which can be classified as "microlumps in the brain collaterals" in traditional Chinese medicine. Based on the theory of latent toxin blocking collaterals, this article discusses the etiology and pathogenesis, clinical sequelae, and traditional Chinese medicine intervention strategies for mild cognitive impairment due to Alzheimer′s disease. The onset of mild cognitive impairment due to Alzheimer′s disease is very similar to the latent pathogen theory, which states that "the latent pathogen is latent and then develops, the poison is deep and difficult to cure, and the development can be recognized but the latent pathogen cannot be detected." Combining clinical experience, our team believes that the basic nature of the disease is a slight deficiency and a slight excess of symptoms. A slight deficiency of the five zang viscera and six fu viscera as root and a latent toxin colling collaterals of qi, fire, phlegm, and blood stasis as manifestaion. These usually start from the qi depression and develop into phlegm coagulation and blood stasis, then end up in latent toxin and gradually become the healthy qi deficiency. Therefore, the deficiency of vital qi and incubation of evil, latent toxin blocking collaterals the pathogenesis of early intervention of this disease should be carried out, upholding the idea that "the upper workman treats the disease before it is diagnosed." The principle of strengthening vital qi to eliminate pathogenic factors, slowing down and promoting pathogenic factors elimination, establishing the method of supporting correctness and wisdom, simultaneously detoxifying and clearing the blood stasis, pattern differentiation as the main and the disease differentiation as the first, combining the disease and pattern, and adjusting the macroscopic and microscopic, focusing simultaneously on eliminating and replenishing, dispel phlegm and remove blood stasis, achieve a strong vital qi and the elimination of evil, and enhance intelligence, delay or even block the progression of mild cognitive impairment due to Alzheimer′s disease, improve patients′ quality of life, and provide a theoretical basis for the early clinical prevention and treatment of Alzheimer′s disease.

OBJECTIVE: To observe the clinical efficacy of thread-embedding at the combined lower he-sea and front-mu points for functional constipation with intestinal excess heat. METHODS: A total of 80 patients with functional constipation of intestinal excess heat were randomly divided into a thread-embedding group (40 cases, 2 cases dropped out) and a Chinese patent medication group (40 cases, 1 case dropped out). Based on the theory of combined lower he-sea and front-mu points for diseases of fu organs, Zhongwan (CV12), Guanyuan (CV4) and bilateral Zusanli (ST36), Shangjuxu (ST37), Tianshu (ST25), Xiajuxu (ST39) were selected and thread-embedding therapy was delivered in the thread-embedding group, once a week. Maren Runchang pill was given orally in the Chinese patent medication group, 6-12 g each time, twice a day. Both groups were treated for 4 weeks. Before and after treatment, the scores of constipation assessment scale (CAS), Bristol stool form scale (BSFS), patient-assessment of constipation quality of life (PAC-QOL) and TCM syndrome were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the CAS scores and the TCM syndrome scores were decreased compared with those before treatment (P<0.05), while the BSFS scores were increased compared with those before treatment (P<0.05) in the two groups; the total scores, as well as the physical discomfort and psychosocial discomfort scores of PAC-QOL were decreased compared with those before treatment (P<0.05) in the two groups, the worry and anxiety, and the satisfaction scores of PAC-QOL were decreased compared with those before treatment (P<0.05) in the thread-embedding group. After treatment, the CAS score, the total score and item-scores of PAC-QOL, as well as the TCM syndrome score in the thread-embedding group were lower than those in the Chinese patent medication group (P<0.05). The total effective rate was 78.9% (30/38) in the thread-embedding group, which was higher than 56.4% (22/39) in the Chinese patent medication group (P<0.05). CONCLUSION Thread-embedding at the combined lower he-sea and front-mu points can effectively treat functional constipation with intestinal excess heat and improve quality of life.
Humans ; Constipation/physiopathology* ; Male ; Female ; Middle Aged ; Acupuncture Points ; Adult ; Acupuncture Therapy ; Aged ; Treatment Outcome ; Young Adult ; Intestines/physiopathology* ; Quality of Life

Objective:To investigate the current status of implementing medical insurance performance evaluation in the hospitals of China under the background of China Healthcare Security Diagnosis Related Groups (CHS-DRG) and Diagnosis-Intervention Packet (DIP) payment reform, explore the perspectives and recommendations of key department leaders (e.g., health insurance, medical affairs, pricing, and performance evaluation departments) regarding health insurance performance evaluation, analyze the influencing factors in its implementation, so as to provide references for hospitals to develop and refine health insurance performance evaluation strategies.Methods:A questionnaire was designed and distributed to hospitals across 31 provincial-level administrative regions in China from December 1 to 31, 2023. The survey targeted secondary and tertiary general or specialized hospitals. The main responsible persons from four functional departments, including medical insurance, healthcare, pricing, and performance, were invited to participate in the survey. Descriptive analysis was conducted on the questionnaire data, and the chi-square test was used for differential analysis of unordered categorical variables, while the Wilcoxon rank sum test was used for differential analysis of ordered categorical variables.Results:A total of 761 valid questionnaires were collected. Most respondents were health insurance department leaders (420, 55.19%). Among them, 741 respondents reported that their hospitals used CHS-DRG or DIP payment, with 258 indicating that their hospitals had already developed and implemented health insurance performance evaluation plans. A majority (685, 90.01%) expressed support for such initiatives. Influencing factor analysis revealed that hospital type, level, scope of health insurance management departments, and payment methods might impact the implementation of health insurance performance evaluation ( P<0.05). Conclusions:Few hospitals have currently adopted health insurance performance evaluation, underscoring the urgency to establish a scientific and reasonable evaluation plan as a robust tool for internal hospital management.

Objective To analyze the distribution and drug resistance patterns of pathogenic bacteria in bile and blood cultures obtained from patients with biliary stones accompanied by acute biliary tract infection,to evaluate the clinical appropriate-ness of antibiotic use based on drug sensitivity results,and to provide evidence for empirical antibiotic treatment in such patients.Methods The clinical data of 161 patients with biliary calculi complicated by acute biliary tract infection who were admitted to the First People's Hospital of Neijiang from 2017 to 2023 were retrospectively analyzed.The results of microbial culture,drug sensitivity analysis,and patient characteristics were assessed to evaluate the appropriateness of clinical antimicrobial therapy.Results Among the 161 patients with positive cultures,212 strains of pathogenic bacteria were detected.The predominant patho-gens were Escherichia coli,Klebsiella pneumoniae subspecies,and Enterococcus faecium.Age and underlying diseases significantly affected the distribution of Escherichia coli and Klebsiella pneumoniae subspecies.Within the gram-negative bacterial group,Esche-richia coli and Klebsiella pneumoniae subspecies exhibited higher drug resistance to commonly used broad-spectrum penicillin,third-generation cephalosporin and quinolones but lower resistance rates to piperacillin and tazobactam;furthermore,elderly indi-viduals aged ≥65 years showed higher resistance rates to ceftriaxone than those under age 65 while people with drug exposure history had higher ceftazidime resistance rates that were statistically significant.In contrast to Enterococcus faecalis which displayed low antimicrobial resistance rates for most drugs tested in this study,Enterococcus faecium demonstrated high levels of antibiotic resistance;however,both Enterococcus faecalis and Enterococcus faecium exhibited zero-resistance rates against vancomycin and tigecycline although this may be attributed to their small sample size in our study cohort.Finally,we found that empirical anti-in-fective drugs,as well as target anti-infective drugs,were not prescribed rationally among these patients due mainly to inappropriate combinations of antibiotics or incorrect dosages.Conclusions The predominant pathogens in patients with acute biliary tract infection are gram-negative bacteria,Gram-positive bacteria,and fungi;however,the potential involvement of anaerobic bacteria should not be overlooked.Vancomycin exhibits sensitivity against gram-positive bacteria,yet the overall rationality of antibiotic usage remains suboptimal.Enhanced clinical testing for pathogenic microorganisms is imperative in the management of biliary stones accompanied by acute biliary tract infection.In contrast,clinical pharmacists should provide comprehensive training on anti-infective drugs to clinicians to facilitate their judicious selection of antibiotics based on drug sensitivity results and prevent the e-mergence of multidrug-resistant bacteria.

Objective:To investigate the current status of implementing medical insurance performance evaluation in the hospitals of China under the background of China Healthcare Security Diagnosis Related Groups (CHS-DRG) and Diagnosis-Intervention Packet (DIP) payment reform, explore the perspectives and recommendations of key department leaders (e.g., health insurance, medical affairs, pricing, and performance evaluation departments) regarding health insurance performance evaluation, analyze the influencing factors in its implementation, so as to provide references for hospitals to develop and refine health insurance performance evaluation strategies.Methods:A questionnaire was designed and distributed to hospitals across 31 provincial-level administrative regions in China from December 1 to 31, 2023. The survey targeted secondary and tertiary general or specialized hospitals. The main responsible persons from four functional departments, including medical insurance, healthcare, pricing, and performance, were invited to participate in the survey. Descriptive analysis was conducted on the questionnaire data, and the chi-square test was used for differential analysis of unordered categorical variables, while the Wilcoxon rank sum test was used for differential analysis of ordered categorical variables.Results:A total of 761 valid questionnaires were collected. Most respondents were health insurance department leaders (420, 55.19%). Among them, 741 respondents reported that their hospitals used CHS-DRG or DIP payment, with 258 indicating that their hospitals had already developed and implemented health insurance performance evaluation plans. A majority (685, 90.01%) expressed support for such initiatives. Influencing factor analysis revealed that hospital type, level, scope of health insurance management departments, and payment methods might impact the implementation of health insurance performance evaluation ( P<0.05). Conclusions:Few hospitals have currently adopted health insurance performance evaluation, underscoring the urgency to establish a scientific and reasonable evaluation plan as a robust tool for internal hospital management.

ObjectiveTo develop traditional Chinese medicine （TCM） formulae for the treatment of nonsevere coronavirus disease 2019 （COVID-19） and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways， and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China， a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19， the calculation was carried out， and the artificial intelligent methods for compositing formulae， that are exhaustive method and parallel computing， were used to obtain candidate compound formulas. Finally， with reference to professional experience， an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b （Il1b）， C-X-C motif chemokine ligand 2 （Cxcl2）， C-X-C motif chemokine ligand 10 （Cxcl10）， C-C motif chemokine ligand 2 （Ccl2）， nitric oxide synthase 2 （Nos2）， and prostaglandin-endoperoxide synthase 2 （Ptgs2） using reverse transcription-quantitative polymerase chain reaction （RT-qPCR） in RAW264.7 cells treated with lipopolysaccharide （LPS）. ResultsIn macrophages and lung epithelial cells， 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome， and the result showed that Yinqiao Powder and Pingwei Powder （银翘散合平胃散， YQPWP） ranked first， reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally， YQPWP had the function of scattering wind and clearing heat， resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula， and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin （翘蒡术皮饮， QBZPY） based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells， with the reversing rates of 100%. The chief medicinal of QBZPY， including Lianqiao （Fructus Forsythiae）， Xixiancao （Herba Siegesbeckiae） and Niubangzi （Fructus Arctii）， can down-regulate multiple signaling pathways related with virus infection， immune response， and epithelial damage. RT-qPCR results indicated that compared with the model group， the QBZPY group down-regulated the mRNA expression of Il1b， tumor necrosis factor （Tnf）， Cxcl2， Cxcl10， Ccl2， Nos2 and Ptgs2 induced by LPS in RAW264.7 cells （P＜0.05 or P＜0.01）. ConclusionBased on targeted transcriptome analysis， expert experience in TCM and artificial intelligence， QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.