Invasive fungal infections play an important factor threatening human health.In recent years, the number of the susceptible population of invasive fungal infections has increased rapidly, leading to a significant increase in the disease burden of human fungi.In 2022, the World Health Organization released a list of key fungal pathogens, aiming to promote global research and investment in fungal infection and antifungal resistance.At present, antifungal drugs are preferred for anti-fungal infection treatment, although the efficacy is limited by the adverse events and drug resistance.Improving the damaged host immune response is a reasonable way to improve the effectiveness of antifungal drugs.This article briefly described the epidemiology of fungal infections, summarized how hosts mediate the clearance of fungi by initiating innate and adaptive immune responses, and discussed the prospects and clinical evidence supporting immunomodulatory therapy for invasive fungal infections.

Objective:To compare the therapeutic efficacy between femoral neck system (FNS) and cannulated compression screws (CCS) in the fixation of femoral neck fractures in the elderly patients aged 65 to 75 years old.Methods:A retrospective study was conducted to analyze the data of 39 patients aged 65 to 75 years old who had been treated for femoral neck fractures at Department of Trauma Surgery, Hospital Affiliated to Qingdao University from January 2015 to September 2022. The patients were divided into 2 groups according to their internal fixation methods. In the FNS group of 18 cases subjected to FNS fixation, there were 8 male and 10 females with an age of (71.1±2.8) years. In the CCS group of 21 cases subjected to CCS fixation, there were 7 males and 14 females with an age of (70.1±2.9) years. The 2 groups were compared in terms of intraoperative fluoroscopy frequency, surgical time, intraoperative bleeding, hospitalization costs, fracture healing time, internal fixation failure, and Harris hip score, changes in neck shaft angle, and femoral neck shortening at 1 year after surgery.Results:The differences were not statistically significant in the preoperative general data or follow-up time between the 2 groups, indicating comparability ( P>0.05). In the FNS group, the intraoperative fluoroscopy frequency [(15.1±2.3) times] was significantly lower than that in the CCS group [(19.5±3.5) times], the surgical time [(49.2±5.2) minutes] was significantly shorter than that in CCS group [(62.4±11.2) minutes], and the intraoperative bleeding [(74.2±15.6) mL] and hospitalization costs [(39,928.7±1,438.3) yuan] were significantly higher than those in the CCS group [(53.1±17.3) mL and (23,527.9±2,126.3) yuan] (all P<0.05). The difference in fracture healing time was not statistically significant between the 2 groups ( P>0.05). In the FNS group, the decreased neck shaft angle (2.65°±1.66°) and femoral neck shortening (3.9±1.3 mm) were significantly smaller than those in the CCS group [4.18°±2.13° and (6.3±2.5) mm] at 1 year after surgery, and the Harris hip score [(82.2±7.2) points] was significantly higher than that in the CCS group [(76.4±5.9) points] (all P<0.05). Internal fixation failure occurred in 1 case in the FNS group and in 4 cases in the CCS group, respectively, showing no statistically significant difference ( P>0.05). Conclusions:Compared with CCS fixation, FNS fixation may lead to better therapeutic efficacy in patients with femoral neck fracture aged 65 to 75 years old. However, the risk of internal fixation failure should also be taken into consideration.

convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.

Objective:To compare the short-term efficacy between proximal femoral bionic nails (PFBN) and 3G Gamma nails in the fixation intertrochanteric femoral fractures in the elderly.Methods:A retrospective study was conducted to analyze the data of 78 elderly patients with intertrochanteric femoral fracture who had been admitted to Department of Trauma Surgery, The Hospital Affiliated to Qingdao University from October 2021 to December 2022. There were 35 males and 43 females with an age of (76.0±7.9) years. By Evans classification: 6 cases of type Ⅰ, 21 cases of type Ⅱ, 24 cases of type Ⅲ, 23 cases of type Ⅳ, and 4 cases of type Ⅴ. The patients were divided into 2 groups according to their internal fixation methods: a PFBN group of 35 patients fixed by PFBN and a Gamma group of 43 cases fixed with 3D Gamma nails. The time from injury to operation, hospital stay, operation time, intraoperative blood loss, weight-bearing time, fracture healing time, and Harris hip score, visual analogue scale (VAS) and incidence of complications at 6 months after operation were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for (14.0±4.0) months. There were no significant differences between the PFBN and Gamma groups in operation time [(58.9±8.2) min versus (58.1±6.8) min], intraoperative blood loss [(138.0±24.9) mL versus(126.8±25.7) mL], hospital stay [(10.9±2.9) d versus (10.3±4.0) d],fracture healing time [(5.0±1.3) months versus (5.1±1.3) months], or good and excellent rate by the Harris hip score [82.9% (29/35) versus 76.7% (33/43)], VAS score [0(0, 1) points versus 1(0, 1) points], or incidence of complications at 6 months after operation [2.9% (1/35) versus 4.7% (2/43)] (all P>0.05). However, the complete weight-bearing time for the PFBN group was (5.3±1.2) weeks, significantly earlier than that for the Gamma group [(6.9±1.4) weeks] ( P<0.05). Conclusion:In the fixation of intertrochanteric femoral fractures in the elderly patients, both PFBN and 3D Gamma nails can achieve satisfactory short-term efficacy, but PFBN is more beneficial to the functional recovery of the hip joint because it leads to earlier complete weight-bearing time than 3D Gamma nails.

Objective:To evaluate the application of the standard of "Delimitation and Classification of Keshan Disease Areas" (GB 17020-2010, Standard for short), learn about the applicability of its technical indicators and requirements, and provide a basis for revision of the Standard.Methods:In March 2022, provinces with severe epidemic areas of Keshan disease or new cases reported in recent years were selected, including Gansu Province, Inner Mongolia Autonomous Region, Shandong Province, Shaanxi Province, Yunnan Province, Shanxi Province, Liaoning Province, and Chongqing City. Multi-stage stratified sampling method and questionnaire survey were adopted to collect information on the application of Standard by relevant health institutions.Results:A total of 448 questionnaires were collected, including 445 valid. The survey results showed that 87.64% (390/445) of the respondents were aware of the Standard, and 64.72% (288/445) had received training on the Standard. Eighty-two point two per cent (365/445) of the respondents believed that the Standard was simple and easy to operate, 83.82% (373/445) believed that the determination of the diseased townships was scientific and reasonable, and could be effectively implemented, and 83.60% (372/445) believed that the determination of historical epidemic areas was applicable to the current situation of Keshan disease; 38.88% (173/445), 38.20% (170/445), and 37.98% (169/445) of the respondents believed that the classification indicators for classifying epidemic areas (severe, moderate, and mild epidemic areas) were not applicable to the current situation of the disease in the local or provinces with Keshan disease, respectively. Among the indicators for epidemic areas classification, 30.79% (137/445), 29.21% (130/445), and 28.54% (127/445) of the respondents thought that the annual prevalence, the annual number of new cases and the annual incidence were most suitable for classification of Keshan disease areas.Conclusions:The Standard has been applied well in practice. However, based on the current situation of Keshan disease, it is suggested to redefine the standard for the severity of the disease and the classification of historical epidemic areas.

Objective:To summarize the best evidence for external auditory canal irrigation in patients with cerumen embolism.Methods:The clinical decisions, guidelines, systematic reviews, expert consensus, group standards, evidence summaries, and randomized controlled trials regarding external auditory canal irrigation in patients with cerumen embolism were retrieved from databases and websites such as BMJ Best Practice, UpToDate, Guidelines International Network, National Institute for Health and Clinical Excellence, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Embase, China National Knowledge Infrastructure, WanFang data, and China Biology Medicine disc. The search period was from database establishment to February 15, 2023. Six researchers screened the literature, evaluated the methodological quality, and extracted and summarized the best evidence for external auditory canal irrigation in patients with cerumen embolism.Results:A total of nine articles were included, including one clinical decision, two guidelines, two systematic reviews, one group standard, and three randomized controlled trials. Sixteen pieces of evidence were summarized from six aspects of operators: pre-operation evaluation and preparation, operation process, post-operation handling, health education, and adverse reactions during operation.Conclusions:This paper summarizes the best evidence for external auditory canal irrigation in patients with cerumen embolism. Medical and nursing staff should carefully select and apply evidence based on clinical scenarios and patient's wishes.

Objective:To explore the efficacy of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori ( H. pylori) in Ningxia. Methods:From August 12, 2022 to March 22, 2023, 600 patients diagnosed as H. pylori-positive by 14C-urea breath test ( 14C-UBT) for the first time in People′s Hospital of Ningxia Hui Autonomous Region, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region, Zhongwei People′s Hospital, Yanchi County People′s Hospital, and Pingluo People′s Hospital were selected, and divided into empirical treatment group (hereinafter referred to as the empirical group), genetic testing group (hereinafter referred to as the genetic group), and drug sensitivity testing group (hereinafter referred to as the drug sensitivity group) by using random number table with 200 patients in each group. The empirical group did not undergo drug sensitivity testing and genetic testing, while the genetic and drug sensitivity groups were confirmed to be sensitive to clarithromycin through genetic testing and drug sensitivity testing, and the patients with drug-resistant were excluded, respectively. All the patients of the 3 groups received the same clarithromycin bismuth-containing quadruple therapy. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed to compare the eradication rates of H. pylori among 3 groups. Cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER) were used for cost-effectiveness and sensitivity analysis based on the ITT. Chi-square test was used for statistical analysis. Results:There were 200, 126, and 168 patients included in the empirical group, genetic group, and drug sensitivity group in ITT analysis, and 190, 123, and 164 patients were enrolled in the 3 groups in PP analysis, respectively. The results of ITT analysis showed that the eradication rates of H. pylori in the empirical group, genetic group, and drug sensitivity group were 80.5% (161/200), 94.4% (119/126), and 95.2% (160/168), respectively. The results of PP analysis indicated that the eradication rates of H. pylori in the 3 groups were 84.7% (161/190), 96.7% (119/123), and 97.6% (160/164), respectively, and the differences were statistically significant ( χ2=25.39 and 24.93, both P<0.001). The H. pylori eradication rates of genetic group and drug sensitivity group were both higher than that of empirical group in ITT and PP analysis( χ2=12.40, 17.80, 11.42, and 17.13; all P<0.001). The cost-effectiveness analysis showed that the direct treatment cost of the empirical group, genetic group, and drug sensitivity group was 400.8, 729.2, and 779.2 yuan, respectively, and the CER was 4.98, 7.72, and 8.18 yuan/%, respectively. Compared to the empirical group, the ICER of the genetic group and drug sensitivity group was 23.6 and 25.7 yuan/%, respectively. The sensitivity analysis demonstrated that, when the cost of genetic testing reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 21.8 or 25.5 yuan/%, respectively. When the cost of drug sensitivity testing reduced or increased by 20%, the ICER of the drug sensitivity group compared to the empirical group was 23.3 or 28.2 yuan/%. When the cost of gastroscopy reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 20.8 or 26.5 yuan/%, and the ICER of the drug sensitivity group compared to the empirical group was 23.0 or 28.4 yuan/%, respectively. Conclusion:In Ningxia, if the clarithromycin bismuth-containing quadruple regimen is applied as the first H. pylori eradication regimen, in order to achieve the clinical eradication efficacy of H. pylori, and the patients can accept an additional payment of 23.6 or 25.7 yuan for each 1% increasing in the H. pylori eradication rate, then the precision treatment after clarithromycin resistance test is recommended.

Infant, Newborn ; Humans ; Infant, Premature ; Infant, Low Birth Weight ; Blood Transfusion ; Infant, Premature, Diseases

Objective:To compare the efficacy between locking plate internal fixation combined with iliac bone graft and separate locking plate internal fixation in the treatment of comminuted proximal humeral fracture in the elderly.Methods:A retrospective cohort study was conducted to analyze the clinical data of 42 elderly patients with comminuted proximal humeral fracture admitted to Affiliated Hospital of Qingdao University from January 2018 to January 2020. There were 20 males and 22 females, aged 65-75 years [(69.5±8.5)years]. According to Neer classification, there were 26 patients with three-part fracture and 16 with four-part fracture. Eighteen patients were treated by locking plate internal fixation combined with autologous iliac bone grafting (bone grafting group), and 24 patients were treated by locking plate internal fixation alone (non-bone grafting group). The operation time, intraoperative blood loss, postoperative drainage volume, hospitalization time, and fracture healing time were documented. Shoulder joint range of motion (forward flexion, extension, internal rotation and external rotation) and degree of humeral head height loss were measured at 1, 6, 12 months after operation and at the last follow-up. The Neer score and visual analogue score (VAS) of shoulder joint were evaluated at 12 months after operation and at the last follow-up. The complications were observed.Results:All patients were followed up for 12-24 months [(18.5±3.8)months]. There were no significant differences in operation time, intraoperative blood loss, postoperative drainage volume and hospitalization time between the two groups (all P>0.05). The fracture healing time in bone grafting group was (3.1±0.7)months, shorter than (4.2±0.9)months in non-bone grafting group ( P<0.05). In the two groups, the postoperative shoulder joint range of motion and degree of humeral head height loss increased significantly over time (all P<0.05). At 1, 6, 12 months after operation and at the last follow-up, the shoulder forward flexion range of motion in bone grafting group was (136.2±7.4)°, (139.3±6.9)°, (146.6±6.1)° and (148.4±4.7)°, higher than that in non-bone grafting group [(134.5±6.7)°, (136.5±7.0)°, (137.9±9.2)° and (138.3±7.9)°]; the shoulder extension range of motion in bone grafting group was (37.1±6.3)°, (40.5±4.4)°, (43.1±3.1) ° and (46.6±4.2)°, higher than that in non-bone grafting group [(35.5±4.6)°, (37.9±5.1)°, (41.3±2.5)° and (43.9±3.1)°]; the shoulder internal rotation range of motion in bone grafting group was (50.5±3.2)°, (54.1±5.6)°, (56.6±4.2)° and (58.9±3.6)°, higher than that in non-bone grafting group [(46.9±5.1)°, (50.3±4.2)°, (53.5±2.7)° and (55.4±5.1)°]; the shoulder external rotation range of motion in bone grafting group was (52.2±3.6)°, (55.6±4.3)°, (58.7±4.4)° and (60.2±5.6)°, higher than that in non-bone grafting group [(50.1±4.7)°, (52.6±5.7)°, (55.3±3.2)° and (57.3±4.1)°] ( P<0.05 or 0.01). At 1, 6, 12 months after operation and at the last follow-up, the degree of humeral head height loss in bone grafting group was (0.8±0.1)mm, (1.1±0.2)mm, (1.4±0.3)mm and (1.6±0.3)mm, smaller than that in non-bone grafting group [(1.1±0.2)mm, (1.4±0.3)mm, (1.7±0.6)mm and (2.0±0.5)mm] ( P<0.05 or 0.01). In the two groups, the postoperative shoulder joint range of motion and degree of humeral head height loss increased significantly over time (all P<0.05). There was no significant difference in Neer score of shoulder joint between the two groups before operation ( P<0.05). At 1, 6, 12 months after operation and at the last follow-up, the Neer score of shoulder joint in bone grafting group was (80.2±5.4)points, (82.1±5.0)points, (85.4±5.8) points and (90.3±4.6)points, higher than that in non-bone grafting group [(75.6±5.1)points, (80.4±5.5)points, (83.5±2.2)points and (87.4±4.8)points] ( P<0.05 or 0.01). There was no significant difference in VAS between the two groups before operation, at 1, 6, 12 months after operation or at the last follow-up (all P>0.05). The complication rate was 11.1% (2/18) in bone grafting group and was 20.8% (5/24) in non-bone grafting group ( P<0.05). Conclusions:For comminuted proximal humeral fractures in the elderly, locking plate internal fixation combined with autogenous iliac bone grafting can accelerate fracture healing, improve shoulder joint range of motion, promote functional recovery, and reduce complications in comparison with locking plate internal fixation alone.

Objective:To investigate the effect of Clostridium butyricum on renal tissue of db/db mice and to explore its mechanism. Methods:Fourteen-week-old db/db mice were divided into db/db group( n=10) and db/db+ Cb group( n=7) according to random number table method. Age-matched db/m mice were selected as the normal control group. The db/m and db/db mice were administered 0.9% sodium chloride solution by gavage, while the db/db+ Cb mice were administered an equivalent amount of Clostridium butyricum solution by gavage for 8 weeks. Serum creatinine , fasting blood glucose, urinary albumin to creatinine ratio(ACR) and other biochemical indicators were also detected. HE staining was used to observe the pathological changes of kidney tissue. The expressions of peroxisome proliferators-activated receptor γ coactivator-1α(PGC-1α) mRNA were detected by realtime PCR, while the expressions of nuclear factor-κB(NF-κB), glucagon-like peptide 1 receptor(GLP-1R), and adenosine monophosphate-activated protein kinase(AMPK) in kidney tissue were determined by immunohistochemistry and Western blotting. The levels of intestinal flora, serum and fecal short-chain fatty acids(SCFAs) were measured by 16S rRNA, liquid chromatograph-mass spectrometer, and gas chromatograohy-mass spectrometry respectively. Results:Compared to db/db mice, db/db+ Cb mice showed improvement in general condition after supplementation with Clostridium butyricum. Fasting blood glucose, blood urea nitrogen, albumin-to-creatinine ratio(ACR), blood creatinine, and levels of interleukin-6(IL-6) in kidney tissue were reduced(all P<0.05). The pathology showed various degrees of amelioration of kidney tissue injury in mice. The expression of PGC-1α mRNA increased in kidney tissue( P<0.05). Decreased expression of NF-κB protein, as well as increased expression of GLP-1R and phosphorylated(p-)AMPK/AMPK protein(all P<0.05) were detected in kidney tissues. Clostridium butyricum modulated the composition of the gut microbiota with elevated total SCFAs in blood and feces. Conclusion:Clostridium butyricum increased the expression of GLP-1R in kidney tissue, promoted AMPK phosphorylation, and alleviated renal tissue damage in mice. This suggests that it may be associated with regulating the abundance of SCFA-producing bacterial populations.