OBJECTIVE To observe the efficacy and safety of amphotericin B combined with posaconazole in the treatment of patients with AIDS combined with cryptococcal meningitis （CM）. METHODS The data of 44 patients with AIDS combined with CM admitted to Chongqing Public Health Medical Center and the First Affiliated Hospital of Army Military Medical University from January 2021 to June 2023 were collected retrospectively. They were divided into amphotericin B combined with flucytosine （AmB+FC） group and amphotericin B combined with posaconazole （AmB+POS） group according to treatment regimen， with 22 cases in each group. AmB+FC group was given Amphotericin B for injection+Flucytosine injection； AmB+POS group was given Amphotericin B for injection+posaconazole injection. After 12 weeks of treatment， clinical efficacies of two groups， clinical symptoms and the negative coversion rate of cerebrospinal fluid， and laboratory test results before and after treatment were observed in 2 groups， and the occurrence of adverse drug reactions was recorded in 2 groups. RESULTS After 12 weeks of treatment， the total effective rate， the incidences of fever， blurred vision， leukopenia， anemia， renal function abnormalities， hypokalemia， liver function abnormalities， rash， and peripheral neuropathy were compared between the two groups， and the differences were not statistically significant （P＞0.05）. The negative coversion rate of cerebrospinal fluid in AmB+POS group was significantly higher than AmB+FC group； the incidences of headache， nausea and vomiting symptoms， and the incidence of any adverse events were significantly lower than AmB+FC group （P＜0.05）. The cerebrospinal fluid pressure and cerebrospinal fluid protein content of the two groups were significantly lower than those before treatment， and the cerebrospinal fluid glucose content and cerebrospinal fluid chloride content were significantly higher than those before treatment （P＜0.05）； however， the differences were not statistically significant between 2 groups （P＞0.05）. CONCL USIONS Amphotericin B combined with posaconazole improves the negative coversion rate of cerebrospinal fluid and relieves clinical symptoms in patients with AIDS combined with CM with good safety.

Diabetic peripheral neuropathy is a common diabetic complication.Presently,our understanding of its pathogenesis is incomplete,and there are no effective treatment options.In-depth research requires the use of animal experiments.The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments into type 2 diabetic peripheral neuropathy.However,but there has been a lack of systematic interrogation and analysis of the evaluation method used with type 2 diabetic peripheral neuropathy models.Therefore,the author reviewed the recent data,summarized and analyzed the evaluation method used for animal models of type 2 diabetic peripheral neuropathy of small and large nerve fibers,and proposed future directions for development,providing a reference for related research.

Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age. Methods This case-control study included 200 patients with PCOS(cases)and 896 non-PCOS controls with the age of 25-37 years.The concentrations of 29 metal(loid)s in the follicular fluid(FF)and clinical indicators in the serum were measured in all participants.Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid)exposure and PCOS risk and investigate the possible roles of clinical indicators,respectively. Results Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk(highest vs.lowest quartile:adjusted odds ratio=2.94,95%confidence interval:1.83-4.72).A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone(AMH)were strongly associated with increased PCOS risk induced by high copper exposure.The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk. Conclusion Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis,mediated by AMH.Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.

Objective To investigate the influence of family resilience on patients with ischemic stroke and provide references for promoting positive handling of patients and the family adaptation.Methods Objective sampling was employed to conduct the semi-structured interviews among 20 patients with ischemic stroke in a Grade ⅢA hospital in Hunan Province between June and September 2021.The data acquired from the interviews were analysed and summarised following Colaizzi analysis method.Results A total of three themes with 10 dimensions were extracted,including promoting post-traumatic growth of patients with 3 dimensions(accepting and attaching importance to the disease to develop a right recognition of the disease,enhancing the will to combat the disease and increasing rehabilitative awareness to develop a healthy life style,cultivating spiritual believes to increase the sense of adversity;stabilising family function and providing emotional support with 4 dimensions in creating safe and satisfactory family settings,facilitating active communications among family members to jointly make decisions fighting against the disease,optimising the roles of family members,and fortifying the cohesion among family members;and proving spiritual comfort and material support with 3 dimensions of providing mutual support among family members to reduce the costs of treatment,improving family intimacy and adaptive support to reduce negative emotions,and seeking support from society to reduce financial burdens.Conclusions Family resilience brings influences to the patients with ischemic stroke from multiple perspectives.It can promote post-traumatic growth,stabilise family functions,provide emotional support,and provide spiritual consolation as well as financial support.Therefore,healthcare workers should enhance the family resilience and ensure the role of family functions to promote an early recovery of patients.

Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.

OBJECTIVE: To assess the value of single sperm sequencing in preimplantation genetic testing for monogenic disease (PGT-M). METHODS: A Chinese couple with two children whom had died of Spinal muscular atrophy (SMA) and attended the Jiangxi Provincial Maternal and Child Health Care Hospital in June 2020 was selected as the subject. Eleven single sperm samples were isolated by mechanical immobilization and subjected to whole genome amplification. Real-time PCR and Sanger sequencing were used to detect the SMN1 variants in the single sperm samples. Genomic DNA of the wife, her parents and the husband, as well as one single sperm sample harboring the SMN1 variant and two single sperm samples without the variant were used for the linkage analysis. Targeted capture and high-throughput sequencing were carried out to test 100 single nucleotide polymorphisms distributed within 2 Mb up- and downstream the variant site. The haplotypes linked with the SMN1 variants were determined by linkage analysis. Blastocyst embryos were harvested after fertilizing by intracytoplasmic sperm injection. Cells from the trophoblasts of each embryo were biopsied and subjected to whole genome amplification and targeted capture and high-throughput sequencing to determine their carrier status. Chromosomal aneuploidy of wild-type embryos was excluded. An euploid embryo of high quality was transferred. Amniotic fluid sample was taken at 18 weeks of gestation to confirm the status of the fetus. RESULTS: Genetic testing showed that the couple both had deletion of exons 7 ~ 8 of the SMN1 gene. The wife has inherited the deletion from her father, while the husband was de novo. The haplotypes of the husband were successfully constructed by single sperm sequencing. Preimplantation genetic testing has indicated that 5 embryos had harbored the heterozygous variant, 4 embryos were of the wild type, among which 3 were euploid. Prenatal diagnosis during the second trimester of pregnancy has confirmed that the fetus did not carry the deletion. CONCLUSION By single sperm sequencing and PGT-M, the birth of further affected child has been successfully avoided.
Humans ; Pregnancy ; Female ; Child ; Male ; Preimplantation Diagnosis ; East Asian People ; Semen ; Genetic Testing ; Muscular Atrophy, Spinal/genetics* ; Aneuploidy ; Blastocyst/pathology* ; High-Throughput Nucleotide Sequencing ; Spermatozoa

Objective:To assess the efficacy and safety of trimethoprim/sulfamethoxazole (TMP/SMZ) combined with caspofungin for the treatment of acquired immunodeficiency syndrome (AIDS)patients with moderate to severe pneumocystis pneumonia (PCP) requiring mechanical ventilation.Methods:The clinical data of AIDS patients who admitted to Chongqing Public Health Medical Center from March 1, 2019 to March 1, 2021 with moderate to severe PCP requiring mechanical ventilation were retrospectively analyzed. Clinical characteristics and outcomes were compared between two groups receiving either combination therapy with TMP/SMZ and caspofungin (combination therapy group) or TMP/SMZ monotherapy (monotherapy group). The patients were divided into two subgroups according to the baseline arterial partial pressure of oxygen (PaO 2), patients with arterial PaO 2≥50 mmHg (1 mmHg=0.133 kPa) and PaO 2 <50 mmHg. The clinical efficacies of combination therapy and monotherapy in each subgroup were further compared. Chi-square and Fisher exact test were used for statistical analysis. The three-month survival was estimated by the Kaplan-Meier method, and the three-month survival rates were compared by Log-rank method. Results:A total of 83 patients were enrolled, including 23 in the monotherapy group and 60 in the combination therapy group. There was no significant difference in all-cause hospital mortalities between these two groups (34.8%(8/23) vs 23.3%(14/60), χ2=1.12, P=0.290). Kaplan-Meier survival curves indicated no significant difference in the three-month survival rates between the two groups ( χ2=0.51, P=0.477). There ware no significant differences observed in the positive clinical response rates and the mechanical ventilation rates after seven days of anti-PCP treatment between the two groups ( χ2=0.02 and 0.01, respectively, both P>0.05). In the 52 patients with PaO 2≥50 mmHg, no significant difference in all-cause hospital mortalities was observed between the monotherapy group and the combination therapy group (2/13 vs 25.6%(10/39), χ2=0.14, P=0.704). There was no statistical significance in the three-month survival rates between the two groups ( χ2=0.69, P=0.407). No significant difference was observed either in the clinical positive response rates or the mechanical ventilation rates after seven days of anti-PCP treatment between the two group( χ2=1.02 and 0.69, respectively, both P>0.05). In the 31 patients with PaO 2<50 mmHg, the all-cause hospital mortality in the combination therapy group was 19.0%(4/21), while six of the 10 patients in the monotherapy group died, and the difference was statistically significant (Fisher exact test, P=0.040). The three-month survival rate in the combination therapy group was significantly higher than that in the monotherapy group ( χ2=4.09, P=0.043). There were no significant differences in clinical positive response rate and the mechanical ventilation rate after seven days of anti-PCP treatment between the two group (Fisher exact test, both P>0.05). The overall adverse event rate in the monotherapy group was 87.0%(20/23), with an incidence of 56.5%(13/23) for both electrolyte disturbances and bone marrow suppression. The above incidences in the combination therapy group were 78.3%(47/60), 35.0%(21/60) and 53.3%(32/60), respectively, and all differences were not statistically significant ( χ2=0.34, 3.18 and 0.07, respectively, all P>0.05). Conclusions:The efficacy of combination therapy with TMP/SMZ and caspofungin is comparable to that of TMP/SMZ monotherapy in AIDS patients with moderate to severe PCP requiring mechanical ventilation. However, in AIDS patients with PCP requiring mechanical ventilation with the baseline PaO 2<50 mmHg, the efficacy of combination therapy is statistically superior to that of TMP/SMZ monotherapy. Combination therapy does not increase the risk of adverse events.

Humans ; HIV Infections/drug therapy* ; HIV-1/genetics* ; Tenofovir/therapeutic use* ; Anti-HIV Agents/therapeutic use* ; RNA ; Drug Combinations

Matrix protein p17 is a structural protein of human immunodeficiency virus（HIV）. It not only plays a key role in multiple stages of HIV life cycle，but also is closely associated with HIV-related lymphoma，neurocognitive impairment and breast cancer. This article reviews the role of matrix protein p17 in HIV infection and HIV-related diseases.

Objective:To explore the construction of evaluation criteria for long-term care ability of the elderly suitable for China's national conditions.Methods:The evaluation criteria were initially established through literature research and field semi-structured interviews. Through the Delphi method, 15 experts were consulted and the evaluation criteria for the long-term care ability of the elderly were finally established.Results:The effective rate of the two rounds of expert consultation questionnaires was 100%, and the expert authority coefficients were 0.91 and 0.92 respectively. The evaluation criteria for long-term care ability of the elderly were established, including two first-level indicators of self-care ability and disease severity, four second-level indicators of abilities of daily living, mental state and social participation, perception and communication, and disease severity, as well as 39 third-level indicators including recumbent status, cognitive function, level of consciousness, illness and so on.Conclusions:The evaluation criteria for long-term care ability of the elderly are scientific and reliable, which can provide a reference for the classification of long-term care services for the disabled elderly in China.