[Pay attention to new evolution trends in the etiology of community-acquired pneumonia in adults].

Over the past two to three decades, the emergence and re-emergence of new infectious diseases, advances in molecular detection techniques of pathogens, antibiotic resistance, changes in population lifestyle and immune status (including vaccination), and other factors have led to new evolutions in the etiology of community-acquired pneumonia (CAP). (1) Although Streptococcus pneumoniae remains a common pathogen of CAP, it is no longer the leading cause in China and the United States. According to the results of 2 multicenter studies in China in the early 21st century, Streptococcus pneumoniae accounted for 10.3% and 12.0% of adult CAP pathogens, respectively, ranking second. A study on key pathogens of adult CAP in nine cities in mainland China from 2014 to 2019 using real-time quantitative PCR and conventional culture on respiratory and blood specimens showed an overall prevalence of Streptococcus pneumoniae of 7.43%, ranking sixth. However, its ranking varied from third to seventh among the nine cities. (2) Challenges and concerns about viruses have increased. National surveillance of acute respiratory tract infections and epidemiology in China from 2009 to 2019 indicated that the positivity rates for viral infections in adult pneumonia was 20.5%. These rates were similar to the results of the CDC's CAP pathogen study in the United States, although the rankings were different (viruses ranked second in China and first in the United States). Over the past 20 years, the emergence of new viral respiratory infections caused by mutant strains or zoonotic strains has significantly increased the challenges and threats posed by viral respiratory infections. (3) The role of Mycoplasma pneumoniae (M pneumoniae) in adult CAP and the need for routine empirical antibiotic coverage are controversial. In addition to the influence of epidemic cycles, the prevalence of M pneumoniae is influenced by factors such as age, season, study design, and detection methods, and geographical distribution is also an important influencing factor. Although M. pneumoniae ranks first among CAP pathogens in mainland China (11.05%), there are significant regional differences. In Beijing, Xi'an, and Changchun M. pneumoniae ranks first, while in Harbin, Nanjing, and Fuzhou it ranks second to sixth. In Wuhan, Shenzhen, and Chengdu M. pneumoniae ranks after the tenth position. Available evidence supports the notion that routine coverage of M. pneumoniae is not necessary for empirical treatment of CAP, except in severe cases. In regions with a high prevalence of M. pneumoniae, the decision to cover atypical pathogens in patients with mild to moderate CAP should be based on local data and individualized. (4) CAP caused by multidrug-resistant bacteria, especially multidrug-resistant Gram-negative bacilli (GNB), has become a concern. According to a systematic review of Chinese literature, Klebsiella pneumoniae accounted for 8.12% of adult CAP patients, ranking fifth, and Pseudomonas aeruginosa accounted for 4.7% (ninth). The China Antimicrobial Resistance Surveillance System (CARSS) reported an average resistance rate of 27.7% for Klebsiella pneumoniae to third-generation cephalosporins and a resistance rate of 10.0% to carbapenems in 2021. The average resistance rate of Pseudomonas aeruginosa to carbapenems was 16.6%. Early empirical treatment should consider predicting the resistance profile using a "locally validated risk factor" scoring system. (5) Co-infections are common but under-reported. The development of non-culture detection techniques over the past 40 years has significantly increased the detection rate of respiratory pathogens, especially viruses, leading to an increasing number of reports of bacterial-viral co-infections in CAP. It has been reported that co-infections account for 39% of severe CAP cases on ventilators in the ICU. Currently, there is inconsistency and confusion regarding the definition and concept of co-infection, the choice of detection techniques, and the differentiation between co-detection and co-infection. Many reports of co-infections in COVID-19 lacked pathogenic evidence, and some even listed "effective antibiotic treatment" as one of the diagnostic criteria for viral-bacterial co-infections, suggesting to some extent an overuse of antibiotics in COVID-19. Due to the diverse etiological spectrum of CAP between regions in the recent years, it is challenging to develop unified guidelines for the management of CAP in large countries. This article provides recommendations for the development of local guidelines for the diagnosis and treatment of CAP.

Occurrence and significance of elevated D-dimer levels in different types of osteomyelitis: a clinical study.

OBJECTIVE: Plasma D-dimer levels >0.5 mg/L are encountered in various conditions besides venous thromboembolism (VTE). Recent studies use them as a prognostic indicator for systemic and inflammatory diseases. The clinical significance of abnormal levels is unclear in osteomyelitis patients with baseline elevation. Our study reviews the occurrence and significance of >0.5 mg/L D-dimer levels in different types of osteomyelitis. PATIENTS AND METHODS: This study involved 125 individuals, out of which 94 were male and 31 were female. The patients were divided into two groups based on the results of bacterial culture testing. Group A comprised those who tested positive for bacterial culture, while group B included those who tested negative. Out of 68 samples tested, 56% were found to have Staphylococcus aureus. All 125 patients underwent blood testing, which included measuring the D-dimer levels, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and MHR monocyte to high-density lipoprotein cholesterol (HDL-C) ratio in different types of osteomyelitis. The statistical analysis of these tests was carried out. RESULTS: Although there were no significant differences in white blood cell (WBC) count, Neutrophil count, Lymphocyte count, or erythrocyte sedimentation rate (ESR) as well as the NLR, PLR, LMR, MHR, HDL-C ratio. The C-reactive protein (CRP) levels were significantly higher in group A (26.13±50.30) than in group B (10.76±18.70) (p<0.05). D-dimer levels were elevated in 40.8% of patients with bacterial culture-positive osteomyelitis, negative culture osteomyelitis, implants with fractures, and no trauma osteomyelitis. No correlation was found between the increase in D-dimer levels and the presence of bacterial culture or implant-related osteomyelitis in patients. CONCLUSIONS: No significant correlation was found between D-dimers and osteomyelitis, including positive bacterial cultures, implant-related osteomyelitis, or osteomyelitis without trauma. However, 40% of the patients had higher D-dimer levels.

[Differential diagnosis of asthma and dysfunctional breathing and vocal cord dysfunction].

The clinical manifestations of bronchial asthma are complex and variable, which can easily be confused with other diseases. So misdiagnosis and missed diagnosis of asthma are common. In the differential diagnosis of asthma, organic diseases such as left ventricular dysfunction, chronic obstructive pulmonary disease, and upper airway obstruction are most often considered, but the understanding of functional disease is insufficient. In fact, GINA guidelines suggested that the differential diagnosis in adult patients with suspected asthma needed to prioritize functional diseases such as dysfunctional breathing (DB)/hyperventilation syndrome (HVS) and vocal cord dysfunction (VCD), rather than organic disease. Here we review the concepts of DB and VCD and their differentiation from asthma.

[Debate on impact of restriction on antimicrobial use on antimicrobial resistance rate: explanation and deliberation].

Antimicrobial resistance (AMR) is a rising public health crisis worldwide. Antimicrobial stewardship, which core is restriction on antimicrobial use to decline selective pressure of AMR, becomes main strategy for tackling AMR. But there are lots of debates about beneficial impact of restriction to antimicrobial use on AMR in recent years. One of the important reasons of the debate is defects on research methodology, especially there are no differentiation between hospital antibiogram and surveillance antibiogram, because the former is used as a reference of empirical antibiotic therapy, and only the latter is appropriate for evaluating factors affecting resistance, including antibiotic use. Once bacteria develop drug resistance, there are both the fitness costs resulting its loss of competitiveness in evolution and restoration of sensitivity to antibiotics, and mechanism of compensatory evolution which allows AMR to persist in bacteria. It is suggested that only by deeply studying the molecular genetics and evolutionary mechanism of drug-resistant bacteria can we find the fundamental way to overcome AMR. At present, we need to adhere to and improve the antimicrobial stewardship, develop new anti-bacterial agents and therapies, connect the Healthy China strategy with the great health concept advocated by WHO and other international organizations, learn from international experience to curb AMR, and promote coordinated and sustainable economic and social development.

[A prospective multi-center clinical investigation of HIV-negative pulmonary cryptococcosis in China].

Objective: To investigate the current status of the diagnosis and treatment of pulmonary cryptococcosis in respiratory medicine and improve the understanding of the clinical characteristics of HIV-negative pulmonary cryptococcosis in China. Methods: A prospective multi-center open cohort study was designed to screen for pulmonary cryptococcosis in the general wards and intensive care units of the Department of Respiratory Diseases in 22 hospitals. The HIV-negative patients with positive cryptococcal etiological diagnosis based on smear culture, antigen detection and histopathology were enrolled in the study. The clinical data of enrolled patients were collected and analyzed. Results: A total of 457 cases of pulmonary cryptococcosis were enrolled, among which 3.28% (15/457) were disseminated infections. The case fatality rate was 0.88% (4/457). The majority of the cases were diagnosed by histopathological examinations (74.40%, 340/457) and cryptococcus antigen detection (37.64%, 172/457). Patients with pulmonary cryptococcosis accounted for 2.04‰ (457/223 748) of the total hospitalized patients in the Department of Respiratory Diseases during the same period, and the ratio was the highest in south and east China. Meanwhile, 70.24% (321/457) of the patients had no underlying diseases, while 87.75% (401/457) were found to have immunocompetent status. Cough and expectoration were the most common clinical symptoms in patients with pulmonary cryptococcosis. However, 25.16% (115/457) of the patients had no clinical symptom or physical signs. In terms of imaging features on pulmonary CT, multiple pulmonary lesions were more common than isolated lesions, and there were more subpleural lesions than perihilar or medial lesions. Morphologically, most of the lesions were middle-sized nodules (1-5 cm) or small-sized nodules (3 mm to 1 cm). The sensitivity of serum cryptococcus antigen test was 71.99% (203/282). Moreover, antigen-positive patients differed from antigen-negative patients in terms of basic immune status, clinical symptoms, imaging features and infection types. Meanwhile, immunocompromised patients differed from immunocompetent patients in terms of clinical symptoms, physical signs, infection-related inflammation indicator levels, imaging features, serum cryptococcus antigen positive rate and prognosis. Conclusions: The majority of cases of HIV-negative pulmonary cryptococcosis in China had no underlying disease or immunocompromised status, and the overrall prognosis was favorable. However, early diagnosis of HIV-negative pulmonary cryptococcosis remains challenging due to the complicated manifestations of the disease.

[Establishment of a method for repairing extremities with extensively deep burn using fresh allogeneic scalp and autologous microskin and observation of its effect].

Objective: To establish a method for repairing extremities with extensively deep burn using large piece of fresh allogeneic scalp spliced by Meek glue combined with autologous microskin and observe its effect. Methods: Medical records of two male patients with extremely extensive deep burn admitted to our hospital from May to November in 2018 were retrospectively analyzed. Two patients aged 44 and 25 years respectively, with total burn area of 90% and 97% total body surface area (TBSA) and full-thickness burn area of 85% and 70% TBSA, respectively. Preoperatively, the surgical area on the extremities was calculated to estimate the necessary amount of allogeneic scalp and Meek miniature skin. The large piece of fresh allogeneic scalp spliced by Meek glue combined with autologous microskin was prepared according to the methods described as follows. Thin medium-thickness fresh scalps with 3% TBSA and 0.30-0.35 mm in depth were harvested from each donor and spliced into a large piece with epidermis upward by spraying Meek glue. Then the spliced scalp was punched after covered with a single-layer gauze. Autologous microskin was transported onto the dermis of fresh large piece of allogeneic scalp by traditional floating method. Bilateral extremities with full-thickness burn of two patients were selected for self-control. The left upper extremity was denoted as treatment group while the right upper extremity was denoted as control group in Patient 1. The right lower extremity was denoted as treatment group while the left lower extremity was denoted as control group in Patient 2. Wounds in the treatment group were treated with fresh large piece of allogeneic scalp spliced by Meek glue and autologous microskin with expansion ratio of 1∶15 after escharectomy, while wounds in control group received grafting of Meek miniature skin with expansion ratio of 1∶6 and or 1∶9 after escharectomy. The donors of allogeneic scalp were 32 males who were the relatives or friends of the patients, aged 21-50 years, with scalp area of (548±48) cm(2). The healing conditions of donor sites of scalp were observed on post operation day 10, and were followed up within 3 months after operation to observe whether forming alopecia and hypertrophic scar or not. Wound healing condition was evaluated during follow-up in post operation week (POW) 2-5 and 4 months after operation. Wound coverage rates were calculated in both treatment and control groups in POW 2, 3, 4, and 5. Results: The donor sites of all allogeneic scalp of donors healed completely on post operation day 10. There was no alopecia or hypertrophic scar within 3 months after operation for follow-up. In POW 2, allogeneic scalp grafts basically survived in treatment group without obvious exudation, and most of the Meek miniature skin survived in control group with obvious exudation. Part of allogeneic scalp grafts dissolved and detached in treatment group in POW 3, and the surviving grafts scabbed. The eschar detached and new epithelium was observed in treatment group in POW 4 and 5. In POW 3-5, surviving Meek miniature skin in control group creeped and was incorporated, and the wounds shrank. Hypertrophic scar was observed in both treatment and control groups 4 months after operation, without obvious difference in scar as a whole. The wound coverage rates were respectively 84%-98% and 76%-92% in treatment group of two patients in POW 2-5, close to or higher than those of control group (35%-97% and 28%-81%, respectively). Conclusions: The study establishes a novel method for splicing fresh allogeneic scalps into a large piece as the covering of microskin, which has good effect for repairing extensively deep burn wounds. Considering that allogeneic skin is scarce, this method may be a new option in clinical treatment for extensively deep burn patients.

[Effects of scar excision combined with negative-pressure on repair of hypertrophic scar in burn children].

Objective: To explore the effects of scar excision combined with negative-pressure on repair of hypertrophic scar in burn children. Methods: From October 2010 to August 2016, 25 children with hypertrophic scar after deep burn were hospitalized, with scar course ranging from 3 months to 11 years and scar area ranging from 35 to 427 [83(51, 98)]cm(2). A total of 35 scars of 25 children were located in trunk (11 scars), upper limb (11 scars), and lower limb (13 scars). All children received scar excision operation and negative-pressure treatment (negative-pressure value ranged from -40 to -20 kPa), among which 6 cases received scar excision operation and negative-pressure treatment for two times for further removal of scars. After scar excision, electronic spring scale was used to measure the tension of the incision. The tension value of children ranged from 3.43 to 23.84 [7.16 (5.59, 9.12)] N, and then the incision was closed with appropriate suture according to the value of the tension. The incision with smaller tension was firstly opened on post operation day (POD) 8. After removing the suture, negative-pressure was conducted to POD 14. The incision with larger tension was firstly opened on POD 12. After removing the suture, biological semi-membrane was used to reduce tension to POD 16. All healed incisions were performed with anti-scar treatment for 1 year and relaxation and fixation for 3 months. General condition of the incision was observed after operation. The reduction percentage of scar area was calculated half-year after operation. The Patient and Observer Scar Assessment Scale was used to record the overall score of scar and scar score of trunk, upper limb, and lower limb before operation and half-year after operation. Data were processed with paired t test and Wilcoxon rank sum test. Results: After removing the suture, all incisions of children healed well without redness, effusion, and rupture. Half-year after operation, the appearance and deformity of incision were obviously improved, and the symptoms including pruritus and pain were basically relieved. Half-year after operation, the scar area of children ranged from 0 to 174 [21(9, 47)]cm(2,) which was significantly decreased as compared with that before operation (Z=-5.16, P<0.05). The reduction percentage of scar area ranged from 36% to 100% [(73±19)%]. Half-year after operation, the overall score of scar and scar score of trunk, upper limb, and lower limb of children were obviously decreased as compared with those before operation (with t values from 6.42 to 17.37, P values below 0.05). Conclusions: Scar excision combined with negative-pressure treatment has a good clinical effect on repair of hypertrophic scar in burn children, which is suitable for clinical application.

Protection of dopamine neurons by vibration training and up-regulation of brain-derived neurotrophic factor in a MPTP mouse model of Parkinson's disease.

It is unknown whether the longer duration of vibration training (VT) has a beneficial effect on Parkinson's disease (PD). And also, the mechanisms underlying the reported sensorimotor-improvement in PD induced by short-duration of VT has not been determined. Here, we investigated the effects of longer duration (4 weeks) of low amplitude vibration (LAV) training on the numbers of dopaminergic neurons in the substantia nigra by immunostaining and the levels of dopamine (DA) and brain-derived neurotrophic factor (BDNF) in the striatum by HPLC and ELISA in the chronic MPTP lesion mouse. We demonstrated for the first time that the longer duration of VT could significantly increase the numbers of nigrostriatal DA neurons and the contents of striatal DA and BDNF in the MPTP mice. Our findings implied that longer duration of VT could protect dopaminergic neurons from the MPTP-induced damage probably by upregulating BDNF and also provided evidence for the beneficial effect of longer duration of VT on PD at the cellular and molecular level.

Genetic polymorphisms of cytochrome P450 and glutathione S-transferase associated with antituberculosis drug-induced hepatotoxicity in Chinese tuberculosis patients.

This study was designed to investigate the association of genetic polymorphisms of cytochrome P450 subtype 2E1 (CYP2E1) and glutathione S-transferase mu 1 (GSTM1) with susceptibility to antituberculosis drug-induced hepatotoxicity (ADIH) in Chinese tuberculosis patients. All patients were treated with a combination of isoniazid, rifampicin, pyrazinamide and ethambutol. Genomic DNA from 104 patients with ADIH and 111 without ADIH was analysed for the frequency of CYP2E1 RsaI and GSTM1 RsaI genotypes by polymerase chain reaction and restriction fragment length polymorphism. The association of polymorphisms with susceptibility to ADIH was calculated using the chi(2)-test and logistic regression analysis. The CYP2E1 RsaI polymorphisms were significantly associated with ADIH and the c1/c1 genotype was an independent risk factor for ADIH. Compared with the GSTM1 RsaI present genotype, the GSTM1 RsaI null genotype tended to increase susceptibility to ADIH, but the association with ADIH was not significant. The results indicate that CYP2E1 RsaI genotype c1/c1 is a potential risk factor for ADIH in the Chinese population. The tendency of the GSTM1 RsaI null genotype to increase susceptibility to ADIH needs further study.

Alternating current electrical conductivity of high-density polyethylene-carbon nanofiber composites.

High-density polyethylene (HDPE)-carbon nanofiber (CNF) composites with good dispersion of fillers in the polymer matrix were melt-compounded in a Haake mixer. The dependences of the alternating current conductivity of such nanocomposites on the filler content, temperature, and DC bias were investigated. The results showed that the electrical conducting behavior of HDPE-CNF nanocomposites can be well characterized by the direct current conductivity (sigmaDC, characteristic frequency (fc) and critical exponent (s). It was found that sigmaDC of percolating HDPE-CNF nanocomposites increases with increasing filler concentration and follows the scaling law of percolation theory. Increasing temperature caused a reduction of sigmaDC, leading to the occurrence of positive-temperature-coefficient effect near the melting temperature of HDPE matrix. Application of DC bias led to an increase of sigmaDC due to the creation of additional conducting paths within the polymer composites. The characteristic frequency generally followed the same tendency as sigmaDC. The s values of percolating composites were slightly higher than those predicted by the percolation theory, indicating the presence of tunneling or hopping conduction in these composites.

[Immune response in Pneumocystis carinii pneumonia in rats].

OBJECTIVE: To study the inflammatory immune response to Pneumocystis canii pneumonia(PCP) in rats induced by glucocorticoid(GC). METHODS: The model of PCP was set up by injecting GC subcutanously to SD rats. Lymphocyte proportion in peripheral blood, CD4+/CD8+ T cell ratio of PBL and lymphocyte proportion in the BALF were measured. The levels of sIL-2R and TNF-alpha in the BALF were detected. RESULTS: 1. After the rats were immunospressed, the lymphocyte proportion in the peripheral blood and CD4+/CD8+ ratio of PBL, and the lymphocyte proportion in the BALF were decreased, and the levels of sIL-2R, TNF-alpha in BALF were reduced. 2. The lowest levels of TNF-alpha in BALF and CD4+/CD8+ T cells of PBL were observed in PCP group; 3. The lymphocyte proportion in the BALF was significantly higher in PCP group than in PC negative group. CONCLUSION: The reduction in the level of TNF-alpha and CD4+/CD8+ T cell ratio in rats treated with GC might result in PCP infection under immunosuppressive condition.

Anisodamine restores bowel circulation in burn shock.

In a group of eight burn patients with a mean of 65.3 +/- 17.4 per cent TBSA burn injury (range 50-90 per cent TBSA), accompanied by a mean of 43.5 +/- 18.9 per cent TBSA full-thickness injury, it was shown that the evidence of global hypovolaemia had disappeared at 12 h after the injury following aggressive fluid resuscitation, while there was still a subnormal pHi of stomach at 48 h. As a prolonged period of inadequacy of oxygen delivery to the intestine might result in impairment of the intestinal mucosal barrier function, and then endogenous endotoxaemia might ensue, it seems to be important to correct intestinal hypoxia as early as possible. Since the inadequate perfusion to the gut wall is due to selective vasoconstriction of the mesenteric vasculature, logic dictates that the use of a vasodilator is in order. Anisodamine, an anticholinergic drug, was then given in six burn patients with comparable burn size and amount of fluid replenishment with the eight patients in the control group. It was clearly demonstrated that gastric pHi returned to normal before 48 h after injury. Plasma endotoxin and TNF contents were measured, and they were significantly lower than control values after 72 h. In conclusion, it is believed that anisodamine might be a valuable adjunct to the resuscitation regime of burn shock, and, therefore, a promising drug to abate endogenous endotoxaemia subsequent to splanchnic vasoconstriction due to hypovolaemia. The shortcomings of the drug were a mild abdominal distention and tachycardia after its administration.

[Uncomplicated bronchial tuberculosis].

Thirty four cases of uncomplicated bronchial tuberculosis proved by fiberobronchoscopy (FB) and operation in recent ten years were reported. The total diagnostic yield of FB was 85.6%. The preliminary results revealed some new characteristics of uncomplicated bronchial tuberculosis during antituberculosis chemotherapy era: uncomplicated bronchial tuberculosis accounted for great proportion among bronchial tuberculosis; the involvement of middle and lower bronchi was more common; positive rate of sputum smear for AFB was low. Among the fibrobron choscopic manifestations, the percentage of proliferative lesions in bronchi was high.

[Diagnosis of pulmonary infections by specific etiologic agents in secondary immunocompromised patients].

Ten cases of pulmonary infections by the specific etiologic agents in immunocompromised patients secondary to diseases and/or drugs were reported. Their infections included 5 tuberculosis, 4 pulmonary aspergillosis, 1 Pneumocystis Carinii and cytomegalovirus pneumonia. The early revelation of pulmonary abnormality, the sampling of non-contaminated diagnostic materials, the improvement of laboratory techniques, and a feasible scheme of clinical management for pulmonary infections in immunocompromised patient were discussed.

[Differential diagnosis between tuberculosis and cancer of lung. Analysis of 65 tuberculosis cases diagnosed by fiber-bronchoscopy].

A series of 65 broncho-pulmonary TB simulating lung cancer with negative AFB in sputum were diagnosed by fiber-bronchoscopy. 60% of the cases were at the age of forty and over. According to the radiographic features, they could be divided into 3 varieties: (1) 31 cases showed mass or nodal shadow. 7 of the 11 cases with cavities mimicked cancer origin in appearance. (2) 30 cases showed atelectasis and segmental shadows with 16 cases in nonpredisposing location of TB. (3) 4 cases with diffuse interstitial and micronodular shadows were different from miliary TB. Of a total of 65 cases, 7 accompanied with hilar/mediastinum adenopathy. Using fiber-bronchoscopy, bronchial lesions were found in 24 cases (36.9%). TB diagnosed by pathological and bacteriological examination were 89.2% and 32.2% respectively. TB combined with squamous cell cancer of the lung was found in one patient. These data indicated that TBB and TBLB provided an effective method in the differential diagnosis of TB and cancer of lung.